Retatrutide Research Library

Detection and Excretion Profile of Retatrutide in Human Plasma and Urine by LC-HRMS: Implications for Antidoping Analysis.

Carneiro GRA, da Costa Nunes IK, Dos Santos Cardoso GR, Dos Santos PF, Padilha MC, Nogueira FCS, Pereira HMG

Rapid communications in mass spectrometry : RCM · Journal issue: 15 Dec 2026

RATIONALE: Retatrutide (LY3437943) is a novel long-acting triple incretin receptor agonist that targets the glucagon-like peptide-1 receptor (GLP-1R), glucose-dependent insulinotropic polypeptide receptor (GIPR), and glucagon receptor (GCGR).

Retatrutide-Associated Improvements in Cardiovascular Risk Biomarkers in Adults With Obesity With or Without Type 2 Diabetes.

Ruotolo G, Harris C, Lin Y, Wilson JM, Pirro V, Duffin KL, Thomas MK, Hartman ML, Neill CO, Coskun T, Milicevic Z, Haupt A, Sattar N, Nicholls SJ

Diabetes, obesity & metabolism · Published online: 17 Aug 2026

Journal issue: 1 Nov 2026

AIMS: To further characterise the effects of retatrutide on cardiometabolic risk, lipoprotein and inflammatory biomarkers were assessed post hoc in phase 2 trials of adults with obesity/overweight with or without type 2 diabetes (T2D). MATERIALS AND METHODS: Data were analysed from two randomised, double-blind, placebo-controlled phase 2 trials.

Development and validation of a multiplexed LC-HRMS method for nine GLP-1 receptor agonists and its pharmaceutical application.

Tong LH, Leung KK, Hung CT

Journal of chromatography. A · 11 Oct 2026

Abstract not reported

Retatrutide in adults with obesity and type 2 diabetes (TRIUMPH-2): a double-blind, parallel-group, randomised, placebo-controlled, phase 3 trial.

Bellido V, le Roux CW, Ekinci EI, Bjornstad P, Frias JP, Giblin K, Eyde S, Park SY, Ferro J, Johnson C, Taylor A

Lancet (London, England) · 10 Oct 2026

BACKGROUND: Retatrutide is an agonist of GIP, GLP-1, and glucagon receptors, and is currently under investigation for the treatment of obesity, type 2 diabetes, and other comorbidities, including knee osteoarthritis and obstructive sleep apnoea. We aimed to assess the efficacy and safety of retatrutide in adults with obesity and type 2 diabetes.

Retatrutide in adults with obesity and type 2 diabetes: what have we learned from TRIUMPH-2?

Holst JJ

Lancet (London, England) · 10 Oct 2026

Abstract not reported

Unapproved GLP-1 Drugs Retatrutide and Zenagamtide Sold Online Are No Bargain.

Rubin R

JAMA · 9 Oct 2026

This Medical News article discusses the reasons behind the burgeoning black market for 2 unapproved GLP-1 weight loss drugs and the potential risks associated with their use.

GLP-1 receptor biology and the therapeutic role of incretin-based agonists in metabolic diseases.

Koceva E, Moll GN

European journal of pharmacology · 8 Oct 2026

Type 2 diabetes (T2DM) and obesity represent a growing global health burden, sharing underlying pathophysiological mechanisms such as impaired insulin signalling and chronic low-grade inflammation.

Emerging risks of health optimisation: refractory nausea associated with peptide injections reported to contain retatrutide.

Buzzi RM, Huber LC

BMJ case reports · 7 Oct 2026

A woman in her mid-20s presented with 5 days of persistent nausea, repeated vomiting, loose stools and markedly reduced oral intake. Blood tests, urinalysis, abdominal ultrasonography and cerebral MRI identified no alternative cause. Symptoms persisted despite intravenous fluids, metoclopramide, ondansetron and domperidone.

Effects of retatrutide on learning and memory in streptozotocin-induced male diabetic rats.

Keskin U, Altın E, Kara MK, Tekin B, Çakırçoban KN, Özatik FY, Arı NS, Sezgin AK, Güngor E

Behavioural brain research · 2 Oct 2026

Diabetes mellitus is associated with cognitive impairment and neurodegenerative changes, partly through hyperglycaemia-driven neuroinflammation and disrupted neuronal signalling. Retatrutide, a triple GIP/GLP-1/glucagon receptor agonist, has shown strong metabolic efficacy, but its effects on diabetes-associated cognitive dysfunction remain unclear.

Gastrointestinal adverse effects of GLP-1 receptor agonists and dual GIP/GLP-1 receptor agonists: A narrative expert review of approved therapies, oral formulations, and pipeline agents.

Singhani V, Ehsan M, Valencia S, Nadeem A, Moazzam E, Butsch WS, Garg S

Nutrition in clinical practice : official publication of the American Society for Parenteral and Enteral Nutrition · 1 Oct 2026

BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 receptor agonists have transformed the management of type 2 diabetes and obesity. Gastrointestinal (GI) adverse events are the most common limitation of these therapies and a leading cause of discontinuation.

Sustained weight loss exceeding 100 kg with sequential incretin-based therapy in Prader-Willi syndrome.

Yovera-Aldana M, Manrique-Hurtado H, Umpierrez GE

JCEM case reports · 1 Oct 2026

Prader-Willi syndrome (PWS) is a neurogenetic disorder characterized by hyperphagia, severe obesity, and early-onset metabolic complications, in which durable weight loss is rarely achieved.

Retatrutide trial: Triple action jab can cause weight loss of up to 25%, results suggest.

Wise J

BMJ (Clinical research ed.) · 1 Oct 2026

Abstract not reported

Efficacy and Safety of Dual GLP-1/Glucagon Receptor Agonism in Overweight and Obesity: A Class-Specific Systematic Review and Meta-Analysis.

Amjad MM, Khan MM, Sarwar F, Ali A, Ali M, Bakhash F, Abid H, Ibrahim F, Mustafa K, Ali DE, Fayyaz MMN, Hassan H, Mian SM, Yaseen M, Qamar I, Khan AH, Ullah S, Khan BW

Diabetes, obesity & metabolism · 29 Sept 2026

BACKGROUND: Dual glucagon-like peptide-1/glucagon receptor (GLP-1/GCGR) agonists represent a novel obesity treatment class, but existing meta-analyses often conflate them with GIP-containing agents (tirzepatide, retatrutide) or restrict analysis to one or two drugs, leaving class-specific efficacy and safety incompletely characterized.

Retatrutide, a Triple Hormone Receptor Agonist, for Treatment of Obesity.

Jastreboff AM, Kaplan LM, Davies MJ, Wilding JPH, Ahmad NN, Murray M, Du Y, Makarova N, Giblin K, Schloot NC, Wang Y, TRIUMPH-1 Investigators

The New England journal of medicine · 29 Sept 2026

BACKGROUND: Retatrutide is a triple-receptor agonist of glucose-dependent insulinotropic polypeptide, glucagon-like peptide-1, and glucagon receptors. METHODS: In this phase 3, randomized, double-blind trial, we assigned adults with obesity without diabetes to receive a once-weekly subcutaneous injection of retatrutide (at a dose of 4 mg, 9 mg, or 12 mg) or placebo for 80 weeks.

Future GLP-1 receptor co-agonists and their cardiac effects.

Neumann J, Kirchefer U, Hofmann B, Gergs U

Naunyn-Schmiedeberg's archives of pharmacology · 22 Sept 2026

Agonists at glucagon-like-peptide-1 receptors (GLP-1R) are becoming approved drugs to treat not only type 2 diabetes and obesity but also cardiac diseases such as coronary heart disease, myocardial infarction and heart failure. Agonism at the GLP-1R can be combined with agonism at additional receptors (co-agonists) to obtain drugs which are more potent to induce weight loss.

Comparative effects of semaglutide tirzepatide and retatrutide on renal fibrosis in UUO and aged mice.

Ding M, Li X, Wei Y, Wang J, Jiao B, Li C, Ma W, Peng Y, Shen J, Yu G, Gao C

iScience · 18 Sept 2026

Chronic kidney disease is a major health burden. Given the therapeutic potential of GLP-1 receptor agonists (semaglutide, tirzepatide, and retatrutide) in diabetic nephropathy, we evaluated their anti-fibrotic and anti-inflammatory effects in non-diabetic renal fibrosis using HK-2 cells and murine UUO and aging models.

The Possible Hematological Cost of Metabolic Success: Do Incretin-Based Therapies Silently Trigger Anemia?

Mizdrak M, Batistić D, Mizdrak I

Medical sciences (Basel, Switzerland) · 17 Sept 2026

Diabetes mellitus and obesity represent a growing global health burden with high morbidity and mortality. In the last several years, novel incretin-based therapies have been developed, and their use has risen dramatically. Beyond their proven metabolic, glycemic, cardiovascular, renal, and many other benefits, there are some observational data linking anemia development with their use.

Cagrilintide and retatrutide combination therapy enhances weight loss and metabolic outcomes in obese male rats.

Petersen J, Merrild C, Holm SK, Kurgan N, Hassan S, Mathiesen CV, Börchers S, Svendsen C, D'Anna S, Andersen NR, Klein AB, Fritzen AM, Deshmukh AS, Pers TH, Clemmensen C

Nature metabolism · 15 Sept 2026

Peptide multi-receptor agonists have advanced obesity treatment, yet challenges remain in achieving maximal weight loss and metabolic control, especially in patients with obesity and type 2 diabetes.

Obstructive sleep apnea, GLP-1 receptor agonist pharmacotherapy, and the oral microbiome: competing biological influences and implications for oral health monitoring.

Comisi JC

Clinical oral investigations · 14 Sept 2026

Abstract not reported

Composition and Labelling Accuracy of Products Sold as Retatrutide in Australia.

Piatkowski T, Craven A, Cornell S, Ferris J

Drug and alcohol review · 1 Sept 2026

Abstract not reported

Pharmacological management of obesity: Current landscape and emerging therapies.

Atal S, Agrawal C, Gupta R, Sadasivam B

Indian journal of pharmacology · 1 Sept 2026

Obesity is now recognized as a chronic, multifactorial, and progressive disease as opposed to mere excess of body weight. It significantly increases the risk of type 2 diabetes, cardiovascular disease, metabolic-associated fatty liver disease, and mental health disorders. 2022 data reveal that nearly 3 billion individuals worldwide were living with either obesity or overweight.

Efficacy and Safety of Glucagon-like Peptide-1 Receptor Agonists and Co-agonists for Weight Loss Among Adults Without Diabetes : An Updated Systematic Review.

Moiz A, Filion KB, Samuels AE, Tsoukas MA, Yu OHY, Peters TM, Eisenberg MJ

Annals of internal medicine · 1 Sept 2026

BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are increasingly used for weight management. PURPOSE: To update our prior systematic review evaluating the efficacy and safety of GLP-1 RAs and co-agonists among adults with overweight or obesity without diabetes.

Effect of Retatrutide, a Novel Triple Receptor Agonist, on Blood Pressure and Lipid Levels: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

Simental-Mendía LE, Barragán-Zúñiga LJ, Reyes-Avitia V

High blood pressure & cardiovascular prevention : the official journal of the Italian Society of Hypertension · 1 Sept 2026

INTRODUCTION: It has been reported that glucagon-like peptide-1 (GLP-1) agonists or dual GLP-1/glucose-dependent insulinotropic polypeptide (GIP) receptor agonists exert beneficial effects on blood pressure and lipid profile. However, the impact of triple agonist retatrutide on these metabolic markers remains to be elucidated.

The role of GLP-1 and GIP receptor agonists in the treatment of diabetes and obesity.

Roskoski R

Pharmacological research · 1 Sept 2026

Owing to the therapeutic success of glucagon-like peptide-1 receptor (GLP-1R) and glucose-dependent insulinotropic polypeptide receptor (GIPR) agonists in the management of diabetes and obesity, the pharmacology of these drugs and their receptors has engendered considerable interest. GLP-1 and GIP are incretin hormones so named owing to their ability to increase insulin secretion.

Incretin-based therapies in diabetic kidney disease: toward integrated cardio-kidney-metabolic disease modification.

Kim Y, Lee EY, Korean Diabetic Kidney Disease Study Group

Kidney research and clinical practice · 1 Sept 2026

Obesity and type 2 diabetes (T2D) are dominant drivers of chronic kidney disease (CKD) within the cardio-kidney-metabolic (CKM) syndrome. Despite advances with renin-angiotensin system inhibitors and sodium-glucose cotransporter 2 (SGLT2) inhibitors, substantial residual cardiovascular and renal risk persists, highlighting the need for therapies targeting upstream metabolic dysfunction.

Potential Role of the Triple Receptor Agonist Retatrutide in Antipsychotic-Associated Metabolic Dysfunction Among Clozapine- and Olanzapine-Treated Schizophrenia Spectrum Disorders: A Narrative Review and Theoretical Framework.

Kaczynski MM, Zureikat RM, Kaczynski MR, Sitarz R, Karakuła-Juchnowicz H

Biomedicines · 31 Aug 2026

Antipsychotic-associated metabolic dysfunction contributes substantially to cardiometabolic morbidity and premature mortality in schizophrenia spectrum disorders, with the greatest burden among patients treated with clozapine and olanzapine. This review focuses on patients with schizophrenia spectrum disorders receiving these two agents, in whom the relevant psychiatric evidence is concentrated.

Disease-modifying anti-diabetic drugs (DMADDs): bridging the SIMPLE approach to disease interception.

Koca N, Uyar S, Şahintürk Y, Yıldız H, Del Prato S, DeFronzo R

Cardiovascular diabetology · 26 Aug 2026

The traditional glucose-centric paradigm of type 2 diabetes management is being superseded by growing evidence that certain agents, sodium-glucose cotransporter-2 inhibitors (SGLT2i), glucagon-like peptide-1 receptor agonists (GLP-1RA), and pioglitazone, confer cardiovascular, renal, and hepatic benefits that extend well beyond glycemic control.

Retatrutide: Obesity drug opens to "compassionate use" in US after speculation Trump took it.

Brown C

BMJ (Clinical research ed.) · 7 Aug 2026

Abstract not reported

Integrating glucagon-like peptide-1 receptor agonists into dermatology practice: Safety and monitoring strategies.

Narla S, Narla RR

Clinics in dermatology · 6 Aug 2026

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have rapidly expanded beyond the treatment of type 2 diabetes mellitus and obesity, with increasing relevance to dermatologic practice as more patients present while receiving these therapies.

Anti-Obesity Medications in Longevity and Aesthetic Medicine.

Bijoch J

Journal of clinical medicine · 3 Aug 2026

Anti-obesity medications (AOMs), led by the glucagon-like peptide-1 receptor agonists (GLP-1 RAs) semaglutide and liraglutide and the dual GIP/GLP-1 receptor agonist tirzepatide, have produced substantial weight reduction and growing signals of benefit that extend well beyond adiposity.

Online-Sourced Retatrutide Complicating Impending Diabetic Ketoacidosis in a Patient With Type 1 Diabetes and Concurrent Shigella Gastroenteritis.

Branine N

Cureus · 1 Aug 2026

Growing public interest in incretin-based therapies for weight loss has been accompanied by increasing availability of research peptides purchasable online. Products may be used without medical assessment or counselling regarding adverse effects, sick-day management or appropriate follow-up. In addition, composition, purity and dosing accuracy may be uncertain.

Beyond weight loss: multisystem benefits of obesity medications.

Savas M, Kuckuck S, Boon MR, van Rossum EFC

The lancet. Diabetes & endocrinology · 1 Aug 2026

Obesity is increasingly managed with medications as disease-modifying therapies, reflecting its role as a gateway disease driving metabolic, cardiovascular, reproductive, neuropsychiatric, and mechanical conditions.

Retatrutide effects on diabetic rats' cognition.

Ferreira J

Lab animal · 1 Aug 2026

Abstract not reported

Benefits and Harms of Pharmacologic Treatments in Adults With Overweight or Obesity: A Living Systematic Review and Network Meta-analysis for the American College of Physicians.

Damen JAA, Idema DL, Vernooij RWM, Huis In 't Veld LF, Kusters MPT, Lokerse ME, de Kanter E, Spijker R, van der Braak K, Jenniskens K, Oerbekke MS, Hooft L

Annals of internal medicine · 1 Aug 2026

BACKGROUND: Overweight and obesity are closely linked to diseases such as type 2 diabetes, coronary heart disease, and stroke and have been shown to increase mortality risk. PURPOSE: To conduct a living systematic review of pharmacologic treatments for weight management in overweight or obesity in adults.

Retatrutide and the urinary tract infection signal: Is the answer hidden in timing?

Koufakis T, Argyrakopoulou G, Kokkinos A, le Roux CW

European journal of internal medicine · 23 Jul 2026

Abstract not reported

Medical Treatments for Obesity: What Does the Future Have in Store?

Bassatne A, Rizo I

The Journal of clinical endocrinology and metabolism · 14 Jul 2026

CONTEXT: Obesity is a chronic relapsing disease associated with substantial morbidity, mortality, and health care costs. Contemporary obesity pharmacotherapies extend beyond weight reduction, with evidence for improvements across multiple obesity-related complications, supporting a shift toward phenotype-guided, complication-centric care.

Retatrutide fact check: Has a man died after taking the unapproved weight loss jab?

Mahase E

BMJ (Clinical research ed.) · 9 Jul 2026

Abstract not reported

Comparative effects of drugs for adults with overweight or obesity: systematic review and network meta-analysis.

Nong K, Shi Q, Xie X, Wang Y, Agarwal A, Guyatt GH, Zhang H, Gao Y, Khunti K, Le Roux CW, Widyahening IS, Fan Q, Liu T, Mao Y, Florez ID, Du H, Pan X, Zou X, Wang C, Sun X, Li J, Hao Q, Jia Q, Sun F, Zhu Z, Agoritsas T, Tian H, Vandvik PO, Li S

BMJ (Clinical research ed.) · 8 Jul 2026

OBJECTIVE: To provide an up-to-date evidence summary about the comparative benefits and harms of drugs for adults with overweight or obesity to inform decision making for policymakers, payers, clinicians, and patients.

Efficacy and safety of retatrutide, a GIP, GLP-1, and glucagon receptor agonist, in people with type 2 diabetes and inadequate glycaemic control with diet and exercise (TRANSCEND-T2D-1): a double-blind, randomised, phase 3 trial.

Bajaj HS, Welch M, Shah P, Luna E, Jaouimaa FZ, Liu B, Liu R, Chen Y, Patel H, Bartee A

Lancet (London, England) · 13 Jun 2026

BACKGROUND: Retatrutide is a GIP, GLP-1, and glucagon triple hormone receptor agonist, under clinical development for type 2 diabetes, obesity, and related complications. We aimed to assess the efficacy and safety of retatrutide as a monotherapy in people with type 2 diabetes that is inadequately controlled by diet and exercise alone.

A Hydrophobic Tag-Assisted Liquid-Phase Strategy for the Synthesis of Retatrutide.

Mao CY, Pang ZJ, Qiao GY, Dong L

Organic letters · 12 Jun 2026

Retatrutide is a novel triple agonist that targets the glucagon receptor (GCGR), the glucose-dependent insulinotropic polypeptide receptor (GIPR), and the glucagon-like peptide-1 receptor (GLP-1R).

Retatrutide: Triple acting jab for type 2 diabetes lowers blood sugar and boosts weight loss, trial reports.

Lang K

BMJ (Clinical research ed.) · 9 Jun 2026

Abstract not reported

Synergistic Intervention for Obesity: Integrating Central Appetite Regulation and Peripheral Energy Expenditure.

Xie J, Yang Y, Chen W, Wang L, Weng S, Lyu Q, Cao G

Current obesity reports · 6 Jun 2026

PURPOSE OF REVIEW: Obesity stems from a chronic imbalance between energy intake and expenditure. Current therapeutic strategies primarily focus on reducing caloric intake, yet their long-term efficacy is often limited by compensatory metabolic adaptations that lead to weight regain.

Retatrutide Shows Multiple Metabolic Benefits in Diet-Induced Obese MASH Mouse and Hamster Models.

Briand F, Le Cudennec C, Grasset E, Breyner N, Bigot C, Dillard P, Sulpice T

Obesity (Silver Spring, Md.) · 1 Jun 2026

OBJECTIVE/METHODS: Our aim was to evaluate the efficacy of the triple glucagon, GIP, and GLP-1 receptor agonist retatrutide in diet-induced obese MASH mouse and hamster models, two preclinical models that we routinely use for assessing new therapies targeting obesity. RESULTS: In mice, retatrutide strongly reduced body weight by 31% (p < 0.0001 vs.

Childhood obesity and cardiac risk in youth: Emerging challenges toward 2050.

Mishra NK

Clinical nutrition ESPEN · 1 Jun 2026

Pediatric obesity is increasing at an alarming rate, affecting over 381 million children worldwide and emerging as a critical public health issue. According to World Health Organization (WHO) 2016, 40% of adults are overweight and 13% are obese, highlighting obesity's persistence throughout life.

GIPR:GCGR co-agonism restores normal weight in obese rodents.

Perez-Tilve D, Zhang F, Zhang Y, Lohman K, Sorrell J, Vick A, Müller TD, Tschöp MH, DiMarchi RD

Molecular metabolism · 1 Jun 2026

OBJECTIVES: Functional co- and tri-agonists at the receptors for GLP-1, GIP and glucagon effectively decrease body weight and hyperglycemia but are associated with adverse gastrointestinal effects related to GLP-1R agonism. Here we report the discovery that obesity can be reversed in the absence of a functional GLP-1R.

Do GLP-1 Receptor Agonists Sabotage Fat Grafts? : A Scoping Review of GLP-1 Receptor Agonist Effects on Adipocyte Biology and Implications for Autologous Fat Transfer.

Chalhoub X, Yang Ng Z

Aesthetic surgery journal · 1 Jun 2026

The rapid adoption of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) for weight management has created an unprecedented overlap with aesthetic surgery. Millions of patients experiencing GLP-1-mediated weight loss now present with facial volume depletion, soft tissue deflation, and contour irregularities; conditions for which autologous fat grafting remains the gold-standard solution.

Obesity pharmacotherapy reimagined: The era of multi-receptor agonists and next-generation metabolic modulators, perspectives and controversies.

Lempesis IG, Dalamaga M

Metabolism open · 1 Jun 2026

Obesity affects over 2 billion adults globally, with projections indicating that nearly two-thirds of adults will be affected by 2050. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have transformed obesity treatment, achieving weight loss previously considered attainable only with bariatric surgery.

Efficacy and Safety of Dual and Triple Glucagon-Like Peptide-1-Based Polyagonists in Metabolic Dysfunction-Associated Steatotic Liver Disease and Steatohepatitis: A Systematic Review and Meta-Analysis.

Santos Solis R, Baeza-Zapata AA, Negrete-Najar JP

Cureus · 1 Jun 2026

Metabolic dysfunction-associated steatotic liver disease (MASLD) and its inflammatory form, metabolic dysfunction-associated steatohepatitis (MASH), are strongly linked to obesity, insulin resistance, type 2 diabetes, and progressive liver fibrosis.

Rationale, design and baseline characteristics of the TRANSCEND-CKD trial of retatrutide in patients with chronic kidney disease.

Heerspink HJL, van Raalte DH, Bjornstad P, Bunck MC, Wu P, Tunali I, Milicevic Z, Koeneman L

Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 29 May 2026

BACKGROUND AND HYPOTHESIS: Retatrutide is an agonist of the glucose-dependent insulinotropic polypeptide, glucagon-like peptide-1 and glucagon receptors that reduced weight and hemoglobin A1c (HbA1c) in individuals with obesity and type 2 diabetes (T2D). Retatrutide may also address key chronic kidney disease (CKD)-related pathophysiological pathways.

Dysesthesia associated with GLP-1 agonist therapies: data-mining analysis and literature review.

Laroche ML, Géniaux H, Jardou M

European journal of clinical pharmacology · 22 May 2026

PURPOSE: An increasing number of anecdotal reports on social media platforms and medical blogs describe dysesthesia, particularly burning skin sensations, in association with glucagon-like peptide-1 receptor (GLP-1R) agonists. We performed a pharmacovigilance data-mining analysis to characterise cases of dysesthesia related to GLP-1R.

Diabetes Mellitus and Stroke: Pathophysiological Connections and Therapeutic Potential of GLP-1 and GLP-1/GIP Receptor Agonists.

Paceana MA, Tartau LM, Boboc IKS, Oancea CN, Berbecaru-Iovan A, Foia CI, Tartau CG, Bogdan M

Pharmaceutics · 19 May 2026

Both diabetes mellitus (DM) and stroke are major global health challenges with high morbidity and mortality. DM is a major risk factor for stroke, contributing to both increased incidence and worse clinical outcomes.

Kynurenic acid mediates epicardial fat-induced lymphatic metabolic dysfunction in atrial fibrillation.

Takahashi M, Abe I, Yoshida N, Katoh D, Fujita D, Goto S, Yamasaki H, Ko T, Jiang Y, He Y, Ito S, Harada T, Takano M, Sato H, Kondo H, Fukui A, Teshima Y, Sako H, Ohta K, Miyamoto S, Yamauchi T, Nomura S, Takeda N, Komuro I, Takahashi N

Nature communications · 19 May 2026

Atrial fibrillation represents a prevalent cardiac arrhythmia whose pathogenic mechanisms remain incompletely understood. Here, we identify impaired atrial lymphangiogenesis as a critical determinant in atrial fibrillation pathogenesis. Analysis of human left atrial appendage specimens reveals decreased lymphatic vessel density in atrial fibrillation patients compared to those in sinus rhythm.

Metabolic Dysfunction-Associated Steatotic Liver Disease and Incretin Receptor Agonists: A Metabolic Approach to Halting Liver Disease Progression.

Abenavoli L, Loricchio AG, Lopez I, Morano D, Ismaiel A, Dumitrascu DL, Luzza F

Medicina (Kaunas, Lithuania) · 18 May 2026

Metabolic dysfunction-associated steatotic liver disease (MASLD) is strongly associated with metabolic abnormalities, shares pathophysiological pathways with metabolic syndrome, and has become a leading cause of chronic liver disease in industrialized nations.

Retatrutide And Lipid And Metabolite Profiles In Participants With Obesity With Or Without Type 2 Diabetes.

Pearson MJ, Willency JA, Lin Y, Abadi A, Hartman ML, Coskun T, Ruotolo G, Duffin KL, Haupt A, Newgard CB, Pirro V

The Journal of clinical endocrinology and metabolism · 14 May 2026

CONTEXT: In phase 2 trials, retatrutide reduced body weight, hemoglobin A1c, and improved the lipid profiles of participants living with obesity, with and without T2D. OBJECTIVE: Assess plasma metabolome and lipidome changes associated with retatrutide treatment. DESIGN: Metabolomics and lipidomics were performed in fasting samples from two randomized, placebo-controlled phase 2 trials.

Triple Hormone Receptor Agonism: The Role of Retatrutide in Addressing Cardiovascular-Kidney-Metabolic (CKM) Syndrome: A Comprehensive Review.

Pillai AA, Godin SL, Frishman WH, Aronow WS

Cardiology in review · 11 May 2026

Retatrutide is a first-in-class, unimolecular triple hormone receptor agonist targeting glucose-dependent insulinotropic polypeptide, glucagon-like peptide-1, and glucagon receptors. By synergizing incretin-mediated central satiety with glucagon-driven thermogenesis, retatrutide circumvents the compensatory metabolic resistance that often limits traditional weight-loss therapies.

Semaglutide, tirzepatide, and retatrutide attenuate the interoceptive effects of alcohol in male and female rats.

Windram M, Lovelock DF, Carew JM, Krieman CG, Hendershot CS, Besheer J

Psychopharmacology · 1 May 2026

RATIONALE: Alcohol use disorder (AUD) remains a major public health challenge, yet effective pharmacotherapies are limited. As such, there is growing interest in repurposing medications with novel mechanisms of action.

Multi-omic profiling reveals Retatrutide alleviates adipose tissue fibrosis via metabolic reprogramming and tissue repair.

Li Q, Cheng W, Zhang J, Ran S, Yu H, Zhou W, Wang Y, Lin J, Liu Y, Hong X, Li H, Yan S

Diabetology & metabolic syndrome · 10 Apr 2026

BACKGROUND: Retatrutide, a novel GIP, GLP-1, and glucagon receptor triple agonist, exhibits unprecedented weight-reducing efficacy in clinical trials, yet the molecular basis of its systemic metabolic benefits remains unclear.

Engineered nutrient-stimulated hormonal multi-agonists for precision targeting of obesity and metabolic disorders.

Cho YK, Jung CH

Clinical and molecular hepatology · 1 Apr 2026

Obesity and its related metabolic comorbidities, including type 2 diabetes, metabolic dysfunction-associated steatotic liver disease, and cardiovascular disease, are increasingly recognized as heterogeneous and multisystemic disorders.

Retatrutide in type 2 diabetes mellitus and obesity: an overview.

Panou T, Gouveri E, Popovic DS, Papanas N

Expert review of clinical pharmacology · 1 Apr 2026

INTRODUCTION: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are increasingly used for T2DM and obesity. AREAS COVERED: An electronic search was conducted in Scopus, PubMed/MEDLINE, and Google Scholar databases.

Efficacy of GLP-1 analog peptides, semaglutide, tirzepatide, and retatrutide on MC4R deficient obesity and their comparison.

Hitaka K, Sugawara T, Matsumoto M, Nio Y

International journal of obesity (2005) · 1 Apr 2026

INTRODUCTION: Melanocortin 4 receptor (MC4R) is a G-protein-coupled receptor expressed in the hypothalamus, playing a key role in regulating feeding behavior and energy homeostasis. MC4R is integral to the POMC-MC4R and leptin-MC4R pathways, which control food intake and body weight. Mutations in the POMC gene lead to severe early-onset obesity and increased food consumption.

Targeting the LPI/GPR55 Axis in MAFLD and MASH: Novel Insights, Therapeutic Strategies and Future Directions.

Lian J, Lareu RR, Patil M, Falasca M

Liver international : official journal of the International Association for the Study of the Liver · 1 Apr 2026

Metabolic dysfunction-associated fatty liver disease (MAFLD), recently redefined from non-alcoholic fatty liver disease (NAFLD), highlights the central role of metabolic dysfunction in its pathophysiology.

Evolution of incretin-based therapies: From GLP-1 monotherapy to dual and triple agonists: A new era in metabolic therapy.

Gupta M, Shukla J

The Indian journal of medical research · 1 Apr 2026

Incretin-based therapies have revolutionised the management of metabolic disorders, transitioning from DPP-4 inhibitors to advanced GLP-1 receptor agonists (GLP-1RAs) and next-generation dual and triple agonists. This review explores the evolving role of incretin pharmacology in type 2 diabetes mellitus (T2DM), obesity, and metabolic dysfunction-associated steatotic liver disease (MASLD).

Pharmacologic Treatment of Metabolic Dysfunction-Associated Steatotic Liver Disease in the Context of Type 2 Diabetes.

Malandris K, Charalampidis K, Loomba R, Sinakos E

Current diabetes reports · 14 Mar 2026

PURPOSE OF REVIEW: Metabolic dysfunction–associated steatotic liver disease (MASLD) is highly prevalent among individuals with type 2 diabetes (T2D). This review summarizes current evidence on the pharmacologic treatment of MASLD, with emphasis on agents currently approved for the management of T2D.

Novel GLP-1-based Medications for Type 2 Diabetes and Obesity.

Son JW, le Roux CW, Blüher M, Nauck MA, Lim S

Endocrine reviews · 11 Mar 2026

The approvals of semaglutide and tirzepatide have set new benchmarks in the treatment of type 2 diabetes and obesity. Building on their success, novel glucagon-like peptide-1 (GLP-1)-based therapeutics are rapidly advancing.

Multi-target incretin-based therapeutics: The rise of dual and triple agonists for metabolic disorders.

Alavi SE, Boshrouyeh R, Raza A, Ebrahimi Shahmabadi H

European journal of medicinal chemistry · 5 Mar 2026

Dual and triple incretin-based therapies are transforming treatment for type 2 diabetes mellitus, obesity, and non-alcoholic fatty liver disease. By targeting glucagon-like peptide-1, glucose-dependent insulinotropic polypeptide, and glucagon receptors, these agents enhance glycemic control, reduce body weight, and improve liver outcomes.

The role of GIP in carbohydrate metabolism: Implications in the development of therapies for T2DM, a narrative review.

Almorza-Gomar D, Díaz-Gómez A, Visiedo F, García-Ortiz JC, Camacho-Ramírez A, Ribelles-García A, Prada-Oliveira JA, Pérez-Arana GM

Histology and histopathology · 1 Mar 2026

INTRODUCTION: For the last three decades, bariatric/metabolic surgeries have highlighted the relevance of certain gastrointestinal hormones in controlling and regulating glucose metabolism. The incretins have been a significant focus in developing therapies against Type 2 Diabetes Mellitus (T2DM).

Comparative Efficacy and Safety of Glucagon Receptor Agonists on Metabolic Outcomes: A Network Meta-Analysis of Randomised Controlled Trials.

Abulehia A, Ayesh H, Ayesh O, Jaber D, Asad T, Itbaisha A, Abugharbieh H, Gharbia R, Abu-Hilal LH, Leon BGC

Endocrinology, diabetes & metabolism · 1 Mar 2026

INTRODUCTION: Glucagon receptor agonists (GRAs) are an emerging class of therapies for obesity and type 2 diabetes, demonstrating encouraging metabolic and weight-reducing effects. Several investigational GRA-based agents, including retatrutide, cotadutide, mazdutide, and survodutide, have reported promising results across early and mid-phase clinical trials.

Incretin-Based Dual and Triple Agonists in Overweight or Obese Individuals: A Systematic Review and Meta-Analysis.

Chan ZH, Omar AS, Gill K, Volucke G, Azhar MM, Haleem SM, Sia JE, Rahman OU, Ahmad M, Shahid N, Gardezi SA, Joseph KV, Behary Paray N, Zulfiqar E

Cardiology in review · 19 Feb 2026

Incretin-based dual and triple agonists have emerged as effective options for obesity management, offering enhanced weight loss through multi-receptor agonism. However, data on their efficacy and safety remain limited. We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of these emerging agents.

Development of the Weight and Emotions Scale (WES).

Kanu C, Kimel M, Goetz I, Neff LM, Boye KS, Stefan M, Jordan J

Obesity science & practice · 1 Feb 2026

OBJECTIVE: Obesity and overweight are associated with significant psychosocial burden. Existing patient-reported outcome (PRO) measures only assess a subset of emotion-related concepts that are relevant to individuals living with these conditions.

Effect of glucagon-like peptide-1 receptor agonists on heart rate in non-diabetic individuals with overweight or obesity: a systematic review and pairwise and network meta-analysis of randomized controlled trials.

Zhang Y, Zhang C, Gong X, Cheng P, Fu H, Diao L, Song C

European journal of medical research · 26 Jan 2026

OBJECTIVES: To explore the association of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on heart rate (HR) in overweight or obese patients without diabetes. METHODS: A comprehensive search of the PubMed, Web of Science, Embase, and Cochrane Library databases was conducted. Mean differences (MDs) were calculated as effect estimates for HR. Pairwise and network meta-analysis were conducted.

[Nephrology : what's new in 2025].

Nanchen G, Pruijm M, Lamine F, Golshayan D, Fakhouri F

Revue medicale suisse · 14 Jan 2026

Complement inhibitors are expanding their indications in nephrology. In patients with type 2 diabetes, semaglutide prevents chronic kidney disease (CKD), while retatrutide reduces albuminuria in patients with diabetes and established CKD. Obinutuzumab improves the renal response in patients with lupus nephropathy.

Metabolic inflammation at the adipose-brain axis.

Mateus-Gomes S, Al-Sayyar A, Lobey B, Nadjar A, Rua R, Ahmad R

Frontiers in physiology · 1 Jan 2026

Overweight and obesity have emerged as global health crises and are increasingly recognized as drivers of central nervous system (CNS) dysfunction.

The Triple-Agonist Revolution: Retatrutide and the Paradigm Shift in Multi-Hormonal Pharmacotherapy for Obesity and Cardiometabolic Comorbidities.

Ganamurali N, Sabarathinam S

Clinical pharmacology in drug development · 1 Jan 2026

Obesity has emerged as a global health crisis requiring innovative therapeutic strategies beyond conventional approaches. While glucagon-like peptide-1 (GLP-1) and dual GIP/GLP-1 receptor agonists have redefined pharmacological management, their limitations necessitate further innovation.

Glucagon-like peptide-1 and peptide YY multi-agonism with GEP44 to optimize weight loss and glycemic control while reducing gastrointestinal side effects: the future of anti-obesity pharmacotherapy?

Burmeister MA, Brown SA, Greer JJ, Hoggatt TJ, Zumwalt WT

Frontiers in endocrinology · 1 Jan 2026

Obesity is a chronic, multifactorial disease that has reached epidemic status. The glucagon-like peptide-1 (GLP-1) receptor (GLP-1R) is a key therapeutic target to achieve weight loss and glycemic control in obesity and type 2 diabetes mellitus.

Efficacy and safety of incretin-based therapies in patients with type 2 diabetes mellitus: a network meta-analysis based on clinical trials.

Wu X, Yang Y, Cui X, Li X, Li Y

Frontiers in pharmacology · 1 Jan 2026

OBJECTIVES: This study systematically assessed the efficacy and safety of 15 incretin-based therapies (IBTs) for type 2 diabetes mellitus (T2DM), including mono- (GLP-1RA), dual- (GIP/GLP-1RA or GLP-1/GCGR), and triple- (GIP/GLP-1/GCGR) receptor agonists, and explored how dosage and treatment duration affect clinical outcomes to support individualized treatment decisions.

Comparative efficacy and safety of glucagon-like peptide 1 based drugs for weight loss in adults with overweight or obesity without diabetes: network meta-analysis of randomised controlled trials.

Chen D, Ma B, Sun H, Zhang J, Gong L, Wang W, Liu Z, Zha H, Du S, Chen M, Sun W, Guo Q, Cao Y, Li Y

BMJ medicine · 1 Jan 2026

OBJECTIVE: To compare the efficacy and safety of glucagon-like peptide 1 (GLP-1) based drug treatments for weight loss in adults with overweight or obesity without diabetes. DESIGN: Network meta-analysis of randomised controlled trials. DATA SOURCES: Embase, PubMed (Medline), and Web of Science, 1 January 2000 to 6 March 2026.

Inotropic effects of retatrutide in isolated human atrial preparations.

Neumann J, Ahlrep U, Hofmann B, Gergs U

Naunyn-Schmiedeberg's archives of pharmacology · 1 Jan 2026

Retatrutide (LY3437943) was developed as a drug to treat type 2 diabetes and obesity.

[An historical overview of GLP-1/GIP incretins. From hormone to "swiss-army knife" medications].

Portha B

Biologie aujourd'hui · 1 Jan 2026

Incretins are hormones released from the gut that play a vital role in regulating postprandial metabolism. It has been 30 years since the first demonstration of the glucose-lowering effects of GLP-1 in people with type 2 diabetes. Here, we review the foundational science that led to an unparalleled development in the pharmacological treatment of diabetes.

Retatrutide for the treatment of obesity, obstructive sleep apnea and knee osteoarthritis: Rationale and design of the TRIUMPH registrational clinical trials.

Giblin K, Kaplan LM, Somers VK, Le Roux CW, Hunter DJ, Wu Q, Lalonde A, Ahmad N, Bethel MA

Diabetes, obesity & metabolism · 1 Jan 2026

AIMS: Retatrutide, a novel synthetic molecule, is a triple agonist activating the glucose-dependent insulinotropic polypeptide, glucagon-like peptide-1 and glucagon receptors. The TRIUMPH clinical development program evaluates its safety and efficacy concurrently for the treatment of obesity and two related complications-obstructive sleep apnea (OSA) and knee osteoarthritis (OA).

IUPHAR review: From foe to friend: Repurposing glucagon to treat obesity and type 2 diabetes.

Elmendorf AJ, Yousefian M, Kim IM, Hardaway JA, Habegger K, Flak JN

Pharmacological research · 1 Jan 2026

The epidemics of metabolic disease, in the form of obesity and type 2 diabetes, are a growing public health concern. However, incretin-based therapeutics have transformed our ability to address these diseases.

Recent Studies on the Effectiveness and Safety of Anti-Obesity Medications: A Scoping Review.

Puspitasari IM, Putra DS, Deliyana AN, Adiputri NI, Octovia LI, Paramita SA, Sinuraya RK

Diabetes, metabolic syndrome and obesity : targets and therapy · 1 Jan 2026

Obesity remains a major global public health challenge associated with increased morbidity, mortality, and reduced quality of life, necessitating effective treatment strategies beyond lifestyle modifications. The present scoping review aimed to synthesize recent evidence on the effectiveness and safety of anti-obesity medications (AOMs).

Dangers of Injectable Peptides and Other Unregulated "Biohacking" Drugs.

Moiz A, O'Keefe EL, O'Keefe JH

Missouri medicine · 1 Jan 2026

Injectable peptides are increasingly used without prescriptions for cosmetic and athletic enhancement, driven by digital marketing and social media. While evidence-based, FDA-approved peptides like semaglutide and tirzepatide offer significant clinical benefits under medical supervision, an expanding illicit market provides easy access without a prescription to many unapproved experimental drugs.

GLP-1 Agonists in Adolescent Obesity: A Narrative Review of Single, Dual, and Triple Agonists.

Abid M, Sheikh KS, Ahmad MS, Jiang H

Diabetes, metabolic syndrome and obesity : targets and therapy · 1 Jan 2026

Adolescent obesity is an escalating global health concern associated with increased risks of cardiovascular disease, type 2 diabetes mellitus, and long-term metabolic complications. Although lifestyle interventions remain first-line therapy, their limited long-term effectiveness has led to increasing interest in pharmacological approaches.

Development and Content Evaluation of the Eating Behavior and Appetite Questionnaire (EBAQ) for Individuals with Obesity.

Kanu C, Clucas C, Skalicky A, Samuelson A, Goetz I, Neff LM, Boye KS, Karn H

Advances in therapy · 1 Jan 2026

INTRODUCTION: Obesity management medications can reduce body weight and have an impact on patients' appetite and eating behaviors. Existing patient-reported outcome (PRO) measures do not fully capture appetite and eating behavior concepts relevant to individuals living with obesity, including those receiving treatment.

Incretin analogues as cardiovascular agents: a state-of-the-art review.

Araiza-Garaygordobil D, Rico-Fontalvo J, Hernández-Balbuena B, Vinay-Coro M, González-Arias M

Frontiers in endocrinology · 1 Jan 2026

Glucagon-like peptide-1 (GLP-1) receptor agonists and the dual glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 receptor agonist tirzepatide have evolved over the past decade from glucose-lowering antidiabetic agents into a cardiovascular drug class with proven outcome benefit across multiple clinical scenarios.

Cardiovascular effects of incretin receptor agonists: beyond glycemic control.

Ravic M, Srejovic I, Milosavljevic I, Novakovic J, Jakovljevic V, Vucicevic K, Petrovic D, Muric M

Canadian journal of physiology and pharmacology · 1 Jan 2026

Incretin-based therapies have evolved from selective glucagon-like peptide-1 receptor agonists (GLP-1RA) to dual GLP-1/glucose-dependent insulinotropic polypeptide (GIP) agonists and unimolecular triple GLP-1/GIP/glucagon receptor agonists. This review examines the cardiovascular effects of these three pharmacological tiers, with emphasis on mechanisms that operate beyond glycaemic control.

Perceived benefits of treatment for obesity with retatrutide: A qualitative study of patients in a phase 2 clinical trial.

Goetz IA, Kanu C, Hoover A, Jimenez-Moreno C, Karn H, Kimel M, Neff LM, Boye KS

Obesity pillars · 1 Dec 2025

BACKGROUND: Retatrutide, an agonist of glucose-dependent insulinotropic polypeptide, glucagon-like peptide-1, and glucagon receptors, is in development for the treatment of obesity. We interviewed participants exiting a phase 2 trial to understand the impact of retatrutide on eating behaviors, physical aspects, emotions, and lifestyle.

Efficacy and Safety of Retatrutide in the Treatment of Diabetes and/or Obesity Comorbid with Chronic Kidney disease: a Systematic Review and Meta-Analysis.

Pallavi K, Chandra A, Kumar K, Martand K, Sahu SS, Mohan L, Verma A

Maedica · 1 Dec 2025

There are still substantial clinical challenges in treating patients who come with type 2 diabetes and/or obesity in addition to chronic kidney disease (CKD). Retatrutide, an innovative agent, represents a potential advancement in therapy; however, its performance and safety profile specifically in a CKD population are not fully determined yet.

Retatrutide improves steatohepatitis in an accelerated mouse model of diet-induced steatohepatitis with a fructose binge.

Viebahn GK, Khurana A, Freund L, Chilin-Fuentes D, Jepsen K, Rosenthal SB, Chatterjee S, Ellenrieder V, Hsu CL, Schnabl B, Hartmann P

American journal of physiology. Gastrointestinal and liver physiology · 1 Dec 2025

Fructose consumption contributes to metabolic dysfunction-associated steatohepatitis (MASH). Retatrutide is a novel triple receptor agonist that improves obesity and hepatic steatosis in humans. The aims of this study were to develop a shortened and clinically relevant dietary mouse model of diet-induced steatohepatitis, and to evaluate the effects of a retatrutide intervention in this model.

Appetite, eating attitudes, and eating behaviours during treatment with retatrutide in adults with type 2 diabetes: Results of a phase 2 study.

Kanu C, Boye KS, Poon JL, Goetz I, Williamson S, Lou J, Hartman ML, Martin CK, Coskun T

Diabetes, obesity & metabolism · 1 Dec 2025

AIMS: To determine whether adults with type 2 diabetes (T2D) treated with retatrutide report greater changes in self-reported appetite, dietary restraint, and disinhibition compared to placebo or dulaglutide and to examine associations with weight change.

Contractile effects of retatrutide in isolated mouse atrial preparations.

Neumann J, Ahlrep U, Hofmann B, Gergs U

Naunyn-Schmiedeberg's archives of pharmacology · 1 Dec 2025

When retatrutide stimulates the glucagon receptor (GCGR), the glucose-dependent insulinotropic polypeptide (GIP) receptor (GIPR), and the glucagon-like peptide-1 receptor (GLP-1R), then 3',5'cyclic adenosine monophosphate (cAMP) is increased.

Shared mechanistic pathways of glucagon signalling: Unlocking its potential for treating obesity, metabolic dysfunction-associated steatotic liver disease, and other cardio-kidney-metabolic conditions.

Neff GW

Diabetes, obesity & metabolism · 1 Dec 2025

Glucagon is a pancreatic peptide hormone whose receptor (GCGR) is expressed in the liver, kidney, and, to a lesser extent, various other tissues. Glucagon is well known as the counterpart to insulin in glucose homeostasis.

Diabetes Mellitus and Chronic Kidney Disease: The Future Is Being Surpassed.

Martínez-Castelao A, Górriz JL, Fernández-Fernández B, Soler MJ, Navarro-González JF

Journal of clinical medicine · 23 Nov 2025

Diabetes mellitus (DM) continues to be a global world health problem. Despite medical advances, both DM and chronic kidney disease (CKD) remain global health issues with high mortality and limited options to prevent end-stage renal failure.

Gastrointestinal Adverse Effects of Anti-Obesity Medications in Non-Diabetic Adults: A Systematic Review.

Takrori E, Peshin S, Singal S

Medicina (Kaunas, Lithuania) · 5 Nov 2025

Background: With rising obesity rates, pharmacological interventions are increasingly used in non-diabetic adults. While being effective in managing weight, these agents frequently cause gastrointestinal (GI) side effects, affecting adherence and long-term outcomes.

Medical Management of Obesity: A Comprehensive Review of Food and Drug Administration (FDA)-Approved and Investigational Therapies.

Raza SS, Zakir Z, Hashmat A, Awan SK, Varrassi G

Cureus · 1 Nov 2025

The global rise in obesity has accelerated both clinical and pharmaceutical innovation in antiobesity pharmacotherapy. This narrative review synthesizes current evidence on Food and Drug Administration-approved medications and emerging investigational agents that are shaping clinical practice.

Efficacy of Tirzepatide, Retatrutide, and Semaglutide for Weight Loss in Obese Individuals Without Diabetes.

Olowo-Oribi BA, Salway RJ

Academic emergency medicine : official journal of the Society for Academic Emergency Medicine · 1 Nov 2025

Abstract not reported

Weight management treatment in obesity.

Rubio-Herrera MA, Mera-Carreiro S

Medicina clinica · 1 Nov 2025

Obesity is a chronic and relapsing disease associated with medical complications and mortality. Our improved understanding of the relevance of the gut-brain axis in regulating appetite and body weight has encouraged research into nutrient-stimulated gastroenteropancreatic hormones as a new therapeutic arsenal for the treatment of people living with obesity.

Efficacy and Safety of GLP-1 Receptor Agonists, Dual Agonists, and Retatrutide for Weight Loss in Adults With Overweight or Obesity: A Bayesian NMA.

Sinha B, Ghosal S

Obesity (Silver Spring, Md.) · 1 Nov 2025

OBJECTIVE: To compare the efficacy and safety of GLP-1 receptor agonists (GLP-1RAs), dual agonists (GLP-1RAs/GIP or GCGR), and retatrutide (GLP-1/GIP/glucagon) for weight loss in adults with overweight or obesity.

Strategic Design of Triple GLP-1R/GCGR/GIPR Agonists with Varied Receptor Potency: Achieving Comparable Glycemic and Weight Reduction Effects.

Wang S, Liu Y, Yan Z, Huang X, Liao Y, Tang C, Jing L, Zhou Z, Han J, Tang W, Jiang N

Journal of medicinal chemistry · 9 Oct 2025

Triple activation of the glucagon-like peptide 1 receptor (GLP-1R), the GIP receptor (GIPR), and the glucagon receptor (GCGR) is an innovative strategy for treating obesity and diabetes. We report the rational design of triple GLP-1R/GCGR/GIPR agonists, featuring potent GLP-1R and GCGR activity with weaker GIPR activation.

Efficacy and safety of anti-obesity drugs in metabolic dysfunction-associated steatotic liver disease: An updated review.

Concepción-Zavaleta MJ, Fuentes-Mendoza JM, Gonzáles-Yovera JG, Ruvalcaba-Barbosa GY, Cura-Rodríguez LD, González-Rodríguez JS, Concepción-Urteaga LA, Pérez-Reyes AI, Quiroz-Aldave JE, Paz-Ibarra J

World journal of gastroenterology · 7 Oct 2025

Obesity is a major driver of metabolic dysfunction-associated steatotic liver disease (MASLD) and its progressive form, metabolic dysfunction-associated steatohepatitis (MASH). As the global prevalence of obesity continues to rise, the burden of MASLD/MASH is increasing, posing significant challenges to healthcare systems.

Association between patient-reported eating behaviours and weight change: Secondary analyses of a randomized, double-blind trial comparing retatrutide and placebo in people with obesity or overweight.

Kanu C, Wu Q, Poon JL, Goetz I, Perez-Nieves M, Boye K, Martin CK, Coskun T, Hartman ML

Diabetes, obesity & metabolism · 1 Oct 2025

Abstract not reported

Decreases in circulating ANGPTL3/8 concentrations following retatrutide treatment parallel reductions in serum lipids.

Wen Y, Lemen D, Lin Y, Chen YQ, Regmi A, Roell WC, Thomas MK, Hartman ML, Coskun T, Milicevic Z, Haupt A, Ruotolo G, Konrad RJ

Diabetes, obesity & metabolism · 1 Oct 2025

Abstract not reported

Efficacy of GLP-1-based Therapies on Metabolic Dysfunction-associated Steatotic Liver Disease and Metabolic Dysfunction-associated Steatohepatitis: A Systematic Review and Meta-analysis.

Wang Y, Zhou Y, Wang Z, Ni Y, Prud'homme GJ, Wang Q

The Journal of clinical endocrinology and metabolism · 16 Sept 2025

OBJECTIVE: New therapies are urgently needed for the treatment of metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH). We conducted this systematic review and meta-analysis to evaluate the therapeutic effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on MASLD/MASH.

Saving muscle while losing weight: A vital strategy for sustainable results while on glucagon-like peptide-1 related drugs.

Cigrovski Berkovic M, Ruzic L, Cigrovski V, Strollo F

World journal of diabetes · 15 Sept 2025

Obesity affects over 1 billion people worldwide and is linked to more than 230 health complications, with cardiovascular disease being a leading cause of mortality. Losing 5%-10% of body weight is considered clinically significant for improving health.

Glucagon-like peptide-1 receptor analogues and beyond: emerging obesity pharmacotherapies.

Abburi K, Melson E, Miras AD, Papamargaritis D

Panminerva medica · 1 Sept 2025

Obesity is a chronic disease associated with multiple health risks. Multimodal treatments including lifestyle interventions, pharmacotherapies and bariatric surgery should be the standard of care for obesity management. Bariatric surgery remains the most effective treatment yielding to sustainable weight loss (WL) of about 20-30%.

Evaluating the Rates of Pancreatitis and Pancreatic Cancer Among GLP-1 Receptor Agonists: A Systematic Review and Meta-Analysis of Randomised Controlled Trials.

Wen J, Nadora D, Bernstein E, How-Volkman C, Truong A, Joy B, Kou M, Muttalib Z, Alam A, Frezza E

Endocrinology, diabetes & metabolism · 1 Sept 2025

AIMS: This meta-analysis evaluates the rates of pancreatitis/pancreatic cancer among glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in randomised controlled trials (RCTs).

Beyond GLP-1: efficacy and safety of dual and triple incretin agonists in personalized type 2 diabetes care-a systematic review and network meta-analysis.

Yan K, Yu H, Blaise B

Acta diabetologica · 1 Sept 2025

BACKGROUND: Dual and triple incretin-based agonists, targeting combinations of GLP-1, GIP, and glucagon receptors, represent an innovative approach in T2DM care. However, comparative efficacy and safety analyses tailored to receptor-specific strategies are limited.

The Effects of Glucagon-Like Peptide-1 (GLP-1) Receptor Agonists on Polycystic Ovarian Syndrome: A Scoping Review.

Hudanich M, Smith SN, Marino A, Riskin SI

Cureus · 1 Sept 2025

Polycystic ovarian syndrome (PCOS) is the most common endocrinopathy in reproductive-aged women worldwide; however, treatment modalities often lack cohesion due to its multifactorial pathophysiology. PCOS is suspected of inducing insulin resistance.

Efficacy and safety of incretin co-agonists: Transformative advances in cardiometabolic healthcare.

Bhat S, Fernandez CJ, Lakshmi V, Pappachan JM

World journal of cardiology · 26 Aug 2025

The ground-breaking development of the incretin agonists by manipulation of the incretin system, including the gut hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), as well as the pancreatic hormone glucagon, has led to the emergence of promising pharmacotherapy for metabolic health.

Effects of retatrutide on body composition in people with type 2 diabetes: a substudy of a phase 2, double-blind, parallel-group, placebo-controlled, randomised trial.

Coskun T, Wu Q, Schloot NC, Haupt A, Milicevic Z, Khouli C, Harris C

The lancet. Diabetes & endocrinology · 1 Aug 2025

BACKGROUND: Retatrutide, a glucose-dependent insulinotropic polypeptide, glucagon-like peptide-1, and glucagon receptor agonist, has demonstrated robust glucose and bodyweight reductions in participants with type 2 diabetes. This substudy assessed percent change from baseline to week 36 in total body fat mass versus placebo and dulaglutide.

Obesity: Clinical Impact, Pathophysiology, Complications, and Modern Innovations in Therapeutic Strategies.

Ullah MI, Tamanna S

Medicines (Basel, Switzerland) · 28 Jul 2025

Obesity is a growing global health concern with widespread impacts on physical, psychological, and social well-being. Clinically, it is a major driver of type 2 diabetes (T2D), cardiovascular disease (CVD), non-alcoholic fatty liver disease (NAFLD), and cancer, reducing life expectancy by 5-20 years and imposing a staggering economic burden of USD 2 trillion annually (2.8% of global GDP).

Antiobesity medications in adult and pediatric obesity and metabolic dysfunction-associated steatotic liver disease.

Rodriguez N, Hartmann P

Pharmacological reviews · 1 Jul 2025

Obesity and metabolic dysfunction-associated steatotic liver disease (MASLD) are estimated to affect 13% and one-third of adults worldwide, respectively. The novel antiobesity medications achieve marked bodyweight loss and improve associated metabolic conditions, including MASLD.

Efficacy and safety of retatrutide for the treatment of obesity: a systematic review of clinical trials.

Misra S, Narayan RK, Kaur M

Journal of basic and clinical physiology and pharmacology · 1 Jul 2025

INTRODUCTION: Obesity is a major public health issue linked to various health complications. Retatrutide, a triple agonist peptide targeting the glucagon receptor, GIP receptor, and GLP-1 receptor, shows promise in addressing this need. CONTENT: This systematic review assessed the safety and efficacy of retatrutide for obesity treatment using available clinical trial data.

Quantitative Comparison of Glucagon-Like Peptide-1 Receptor Agonists on Weight Loss in Adults: A Systematic Review and Model-Based Meta-Analysis.

Zhang S, Yu B, Xu J, Jin S, Li Y, Bing H, Li J, Ma X, Zhang X, Zhao L

Diabetes technology & therapeutics · 1 Jun 2025

The objective of this study is to quantitatively compare the weight loss effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) in adult patients with no diabetes and type 2 diabetes (T2D). PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), and Embase have been used as data sources from database inception to January 6, 2024.

The Effect of Retatrutide on Kidney Parameters in Participants With Type 2 Diabetes Mellitus and/or Obesity.

Heerspink HJL, Lu Z, Du Y, Duffin KL, Coskun T, Haupt A, Hartman ML

Kidney international reports · 1 Jun 2025

INTRODUCTION: Obesity and type 2 diabetes mellitus (T2D) increase the risk of kidney disease. This study assessed changes in kidney parameters with retatrutide, an agonist of the glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1), and glucagon receptors.

Retatrutide-A Game Changer in Obesity Pharmacotherapy.

Katsi V, Koutsopoulos G, Fragoulis C, Dimitriadis K, Tsioufis K

Biomolecules · 30 May 2025

Obesity and type 2 diabetes mellitus (T2DM) are global health crises with significant morbidity and mortality. Retatrutide, a novel triple receptor agonist targeting glucagon-like peptide-1 (GLP-1), Glucose-Dependent Insulinotropic Polypeptide (GIP), and glucagon receptors, represents a groundbreaking advancement in obesity and T2DM pharmacotherapy.

[Glucagon-like peptide-1 receptor agonists: a new pharmacological treatment option for psychiatric illnesses?].

Himmerich H

Der Nervenarzt · 1 May 2025

Albiglutide, dulaglutide, exenatide, liraglutide, lixisenatide, orforglipron and semaglutide are glucagon-like peptide‑1 (GLP-1) receptor agonists. Tirzepatide targets not only GLP‑1 but also glucose-dependent insulinotropic peptide (GIP) receptors and retatrutide is a triple GLP‑1, GIP and glucagon receptor agonist.

Multifunctional incretin peptides in therapies for type 2 diabetes, obesity and associated co-morbidities.

Bailey CJ, Flatt PR, Conlon JM

Peptides · 1 May 2025

Recent studies with peptide-based incretin therapies have focussed mainly on the glucagon-like peptide-1 (GLP-1) receptor agonist semaglutide and the dual agonist tirzepatide that engages receptors for GLP-1 and glucose-dependent insulinotropic polypeptide (GIP).

Efficacy of GLP-1 Receptor Agonist-Based Therapies on Cardiovascular Events and Cardiometabolic Parameters in Obese Individuals Without Diabetes: A Meta-Analysis of Randomized Controlled Trials.

Yin Y, Zhang M, Cao Q, Lin L, Lu J, Bi Y, Chen Y

Journal of diabetes · 1 Apr 2025

BACKGROUND: The cardioprotective effects of glucagon-like peptide-1 receptor agonist (GLP-1RA)-based therapies in nondiabetic individuals with overweight or obesity remain underexplored. This meta-analysis evaluates their impact on cardiovascular events and metabolic parameters in this population.

Breaking the weight loss paradox: from weight reduction to cardiovascular benefit in obesity treatment.

Gajos G

Polish archives of internal medicine · 24 Mar 2025

Obesity is a growing global epidemic and a major risk factor for cardiovascular disease. However, previous weight loss interventions have largely failed to demonstrate consistent cardiovascular benefits. While lifestyle modifications remain the cornerstone of obesity management, their long-term efficacy is limited, and most individuals eventually regain the lost weight.

What is the pipeline for future medications for obesity?

Melson E, Ashraf U, Papamargaritis D, Davies MJ

International journal of obesity (2005) · 1 Mar 2025

Obesity is a chronic disease associated with increased risk of obesity-related complications and mortality. Our better understanding of the weight regulation mechanisms and the role of gut-brain axis on appetite has led to the development of safe and effective entero-pancreatic hormone-based treatments for obesity such as glucagon-like peptide-1 (GLP-1) receptor agonists (RA).

Pharmacological Dissection Identifies Retatrutide Overcomes the Therapeutic Barrier of Obese TNBC Treatments through Suppressing the Interplay between Glycosylation and Ubiquitylation of YAP.

Cui X, Zhu Y, Zeng L, Zhang M, Uddin A, Gillespie TW, McCullough LE, Zhao S, Torres MA, Wan Y

Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 1 Mar 2025

Triple-negative breast cancer (TNBC) in obese patients remains challenging. Recent studies have linked obesity to an increased risk of TNBC and malignancies.

Comparative Effectiveness of Semaglutide, Liraglutide, Orlistat, and Phentermine for Weight Loss in Obese Individuals: A Systematic Review.

Patel JP, Hardaswani D, Patel J, Saiyed F, Goswami RJ, Saiyed TI, Patel H, Amin TH

Cureus · 1 Mar 2025

Obesity, a multifaceted and chronic condition characterized by excessive fat accumulation, poses significant risks to overall health and is associated with various metabolic and cardiovascular complications.

The promise of glucagon-like peptide 1 receptor agonists (GLP-1RA) for the treatment of obesity: a look at phase 2 and 3 pipelines.

Madsbad S, Holst JJ

Expert opinion on investigational drugs · 1 Mar 2025

INTRODUCTION: GLP-1-based therapies have changed the treatment of overweight/obesity.

Sex Differences in the Efficacy of Glucagon-Like Peptide-1 Receptor Agonists for Weight Reduction: A Systematic Review and Meta-Analysis.

Yang Y, He L, Han S, Yang N, Liu Y, Wang X, Li Z, Ping F, Xu L, Li W, Zhang H, Li Y

Journal of diabetes · 1 Mar 2025

AIM: To verify sex differences of GLP-1RAs for weight reduction. METHODS: We searched RCTs reporting weight change by sex from PubMed, Web of Science, Embase, Cochrane Library, and ClinicalTrials registries. Meta-regression was performed to evaluate the association between weight reduction and sex differences.

Comparative efficacy and safety of GLP-1 receptor agonists for weight reduction: A model-based meta-analysis of placebo-controlled trials.

Guo H, Yang J, Huang J, Xu L, Lv Y, Wang Y, Ren J, Feng Y, Zheng Q, Li L

Obesity pillars · 1 Mar 2025

AIM: Obesity is a global epidemic. The FDA has approved glucagon-like peptide-1 (GLP-1) receptor agonists such as Liraglutide, Semaglutide, and the GLP-1/gastric inhibitory polypeptide (GIP) dual agonist Tirzepatide for the treatment of obesity. Clinical trials of GLP-1/GIP/glucagon(GCG) triple agonists are ongoing.

Efficacy and Safety of Glucagon-Like Peptide-1 Receptor Agonists for Weight Loss Among Adults Without Diabetes : A Systematic Review of Randomized Controlled Trials.

Moiz A, Filion KB, Toutounchi H, Tsoukas MA, Yu OHY, Peters TM, Eisenberg MJ

Annals of internal medicine · 1 Feb 2025

BACKGROUND: Recent randomized controlled trials (RCTs) have investigated glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and dual or triple co-agonists for weight loss among adults with overweight or obesity and without diabetes. PURPOSE: To assess the efficacy and safety of GLP-1 RAs and co-agonists for the treatment of obesity among adults without diabetes.

Efficacy and safety of triple hormone receptor agonist retatrutide for the management of obesity: a systematic review and meta-analysis.

Tewari J, Qidwai KA, Tewari A, Kaur S, Tewari V, Maheshwari A

Expert review of clinical pharmacology · 1 Jan 2025

INTRODUCTION: Retatrutide is a novel triple hormone receptor agonist which has shown great promise in tackling obesity in preliminary trials. We did this systematic review and meta-analysis to pool the results of all available trials and ascertain its safety and efficacy in the treatment of obesity.

Comparative efficacy of incretin drugs on glycemic control, body weight, and blood pressure in adults with overweight or obesity and with/without type 2 diabetes: a systematic review and network meta-analysis.

Liu S, Hu J, Zhao C, Liu H, He C

Frontiers in endocrinology · 1 Jan 2025

BACKGROUND: The rapid development of multi-receptor drugs targeting glucagon-like peptide-1 receptor (GLP-1R) is driving significant advancements in the treatment of individuals with type 2 diabetes and obesity. This systematic review and network meta-analysis aims to compare the efficacy and safety of multi-receptor drugs in adults with overweight or obesity, with or without type 2 diabetes.

Harnessing GLP-1 Receptor Agonists for Obesity Treatment: Prospects and Obstacles on the Horizon.

Abdelrahman RM, Musa TH, Arbab IA, Suliman MH, Ahmed EO, Mohamed AN, Musa HH, Jalal M, Gasmallah SI

Journal of obesity · 1 Jan 2025

BACKGROUND: Obesity has emerged as a pressing global health challenge, and therapies based on glucagon-like Peptide 1 receptor agonists (GLP-1RAs) have transformed its management. Currently, liraglutide, semaglutide, and tirzepatide are FDA-approved for obesity treatment, while other agents are used off-label.

Emerging pharmacotherapies for obesity: A systematic review.

Kokkorakis M, Chakhtoura M, Rhayem C, Al Rifai J, Ghezzawi M, Valenzuela-Vallejo L, Mantzoros CS

Pharmacological reviews · 1 Jan 2025

The history of antiobesity pharmacotherapies is marked by disappointments, often entangled with societal pressure promoting weight loss and the prevailing conviction that excess body weight signifies a lack of willpower. However, categories of emerging pharmacotherapies generate hope to reduce obesity rates.

Weight Loss Blockbuster Development: A Role for Unimolecular Polypharmacology.

Zhou Q, Li G, Hang K, Li J, Yang D, Wang MW

Annual review of pharmacology and toxicology · 1 Jan 2025

Obesity and type 2 diabetes mellitus (T2DM) impact more than 2.5 billion adults worldwide, necessitating innovative therapeutic approaches. Unimolecular polypharmacology, which involves designing single molecules to target multiple receptors or pathways simultaneously, has revolutionized treatment strategies.

Comparison of the effects of Liraglutide, Tirzepatide, and Retatrutide on diabetic kidney disease in db/db mice.

Ma J, Hu X, Zhang W, Tao M, Wang M, Lu W

Endocrine · 1 Jan 2025

PURPOSE: To assess and compare the therapeutic efficacy of Liraglutide, Tirzepatide, and Retatrutide in treating diabetic kidney disease (DKD) in db/db mice. METHODS: Db/db mice were administered intraperitoneal injections of Liraglutide (10 nmol/kg), Tirzepatide (10 nmol/kg), and Retatrutide (10 nmol/kg) for 10 weeks.

Review: Special Issue: Real-world evidence on the use of GLP1 receptor agonists: Emerging concepts in obesity management: focus on glucagon receptor agonist combinations.

Anderson SL

Drugs in context · 1 Jan 2025

The global rise in obesity and its associated health risks has driven the need for more effective pharmacological treatments. Glucagon receptor (GCGR)-based multi-agonist drugs are emerging as promising treatments for obesity, with several in advanced stages of clinical development.

Triple Agonism Based Therapies for Obesity.

Goldney J, Hamza M, Surti F, Davies MJ, Papamargaritis D

Current cardiovascular risk reports · 1 Jan 2025

PURPOSE OF THE REVIEW: Glucagon-like peptide 1 (GLP-1) receptor agonists (RA) have transformed obesity and type 2 diabetes (T2D) management. Tirzepatide, the first dual GLP-1/glucose-dependent insulinotropic polypeptide (GIP) RA approved for both conditions, has paved the way for next-generation incretin-based therapies.

Efficacy and safety of retatrutide, a novel GLP-1, GIP, and glucagon receptor agonist for obesity treatment: a systematic review and meta-analysis of randomized controlled trials.

Abdrabou Abouelmagd A, Abdelrehim AM, Bashir MN, Abdelsalam F, Marey A, Tanas Y, Abuklish DM, Belal MM

Proceedings (Baylor University. Medical Center) · 1 Jan 2025

BACKGROUND: Retatrutide is a novel triple agonist targeting the receptors of glucagon-like peptide 1 (GLP-1), gastric inhibitory polypeptide (GIP), and glucagon. We sought to assess the efficacy and safety of retatrutide in obese patients with or without diabetes. METHODS: PubMed, Scopus, Web of Science, and Cochrane databases were searched from inception until May 2024.

Incretin triple agonist retatrutide (LY3437943) alleviates obesity-associated cancer progression.

Marathe SJ, Grey EW, Bohm MS, Joseph SC, Ramesh AV, Cottam MA, Idrees K, Wellen KE, Hasty AH, Rathmell JC, Makowski L

npj metabolic health and disease · 1 Jan 2025

Medical therapeutics for weight loss are changing the landscape of obesity but impacts on obesity-associated cancer remain unclear.

Compounded glucagon-like peptide-1 receptor agonists for weight loss: the direct-to-consumer market in Colorado.

DiStefano MJ, Dardouri M, Moore GD, Saseen JJ, Nair KV

Journal of pharmaceutical policy and practice · 1 Jan 2025

BACKGROUND: High prices and other access barriers have contributed to the rise of a market for compounded glucagon-like peptide-1 receptor agonists for weight loss in the United States. This market has not been systematically studied.

The power of three: Retatrutide's role in modern obesity and diabetes therapy.

Abdul-Rahman T, Roy P, Ahmed FK, Mueller-Gomez JL, Sarkar S, Garg N, Femi-Lawal VO, Wireko AA, Thaalibi HI, Hashmi MU, Dzebu AS, Banimusa SB, Sood A

European journal of pharmacology · 15 Dec 2024

The increasing prevalence of obesity and type 2 diabetes mellitus has resulted in a significant challenge to public health throughout the globe. It required the development of novel therapeutic approaches. Retatrutide is a groundbreaking triple agonist that targets glucagon receptors, gastric inhibitory polypeptide, and glucagon-like peptide-1.

Seven glucagon-like peptide-1 receptor agonists and polyagonists for weight loss in patients with obesity or overweight: an updated systematic review and network meta-analysis of randomized controlled trials.

Xie Z, Zheng G, Liang Z, Li M, Deng W, Cao W

Metabolism: clinical and experimental · 1 Dec 2024

PURPOSE: This study aimed to provide evidence-based support and a reference for the efficacy and safety of seven glucagon-like peptide-1 (GLP-1) receptor agonists and polyagonists for weight loss in patients with obesity or overweight through a network meta-analysis.

The "Weight" for a New Agent Is Almost Over: A Commentary on the Novel Triagonist Retatrutide for Obesity.

Deravi M, Piszczatoski C, Phillips B, Huston J, Vascimini A

The Journal of pharmacy technology : jPT : official publication of the Association of Pharmacy Technicians · 1 Dec 2024

Retatrutide, a hormone receptor agonist targeting glucagon, glucagon-like peptide 1, and glucose-dependent insulinotropic polypeptide, is being developed to treat obesity.

Effects of once-weekly subcutaneous retatrutide on weight and metabolic markers: A systematic review and meta-analysis of randomized controlled trials.

Pasqualotto E, Ferreira ROM, Chavez MP, Hohl A, Ronsoni MF, Pasqualotto T, Moraes FCA, Hespanhol L, Figueiredo Watanabe JM, Lütkemeyer C, van de Sande-Lee S

Metabolism open · 1 Dec 2024

AIM: To assess the effects of once-weekly subcutaneous retatrutide on weight and metabolic markers and the occurrence of side effects in patients with overweight, obesity and/or type 2 diabetes (T2D).

Why are we still in need for novel anti-obesity medications?

Novikoff A, Grandl G, Liu X, D Müller T

The Lancet regional health. Europe · 1 Dec 2024

From the pioneering moment in 1987 when the insulinotropic effect of glucagon-like peptide 1 (GLP-1) was first demonstrated in humans, to today's pharmaceutical gold rush for GLP-1-based treatments of obesity, the journey of GLP-1 pharmacology has been nothing short of extraordinary.

Incretin-based therapies for the treatment of obesity-related diseases.

Caruso I, Cignarelli A, Sorice GP, Perrini S, Giorgino F

npj metabolic health and disease · 6 Nov 2024

Obesity-related disability-adjusted life years (DALYs) are expected to increase by approximately 40% from 2020 to 2030. DALYs and mortality related to obesity are the consequence of multiple comorbidities such as cardiovascular (i.e., heart failure) and metabolic diseases (i.e. type 2 diabetes [T2D], metabolic dysfunction-associated steatotic liver disease [MASLD]).

Efficacy and Safety of GLP-1 Medicines for Type 2 Diabetes and Obesity.

Drucker DJ

Diabetes care · 1 Nov 2024

The development of glucagon-like peptide 1 receptor agonists (GLP-1RA) for type 2 diabetes and obesity was followed by data establishing the cardiorenal benefits of GLP-1RA in select patient populations.

The First Triple Agonist for Antiobesity: Retatrutide.

Tetelbaun L, Mullally JA, Frishman WH

Cardiology in review · 8 Oct 2024

The prevalence of individuals with overweight and obesity has increased by 18% since 1990 and it is projected that by 2030, nearly 50% of US adults will have obesity.

Evaluating the Impact of Novel Incretin Therapies on Cardiovascular Outcomes in Type 2 Diabetes: An Early Systematic Review.

Salmen T, Potcovaru CG, Bica IC, Giglio RV, Patti AM, Stoica RA, Ciaccio M, El-Tanani M, Janež A, Rizzo M, Gherghiceanu F, Stoian AP

Pharmaceuticals (Basel, Switzerland) · 3 Oct 2024

Background This systematic review is registered with CRD42024507397 protocol number and aims to compare the known data about retatrutide on long-term cardiovascular (CV) protection with tirzepatide, an incretin with recent proven CV benefits.

Incretin-Based Weight Loss Pharmacotherapy: Can Resistance Exercise Optimize Changes in Body Composition?

Locatelli JC, Costa JG, Haynes A, Naylor LH, Fegan PG, Yeap BB, Green DJ

Diabetes care · 1 Oct 2024

This narrative review highlights the degree to which new antiobesity medications based on gut-derived nutrient-stimulated hormones (incretins) cause loss of lean mass, and the importance of resistance exercise to preserve muscle.

The Pathophysiological Associations Between Obesity, NAFLD, and Atherosclerotic Cardiovascular Diseases.

Li M, Cui M, Li G, Liu Y, Xu Y, Eftekhar SP, Ala M

Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme · 1 Oct 2024

Obesity, non-alcoholic fatty liver disease (NAFLD), and atherosclerotic cardiovascular diseases are common and growing public health concerns. Previous epidemiological studies unfolded the robust correlation between obesity, NAFLD, and atherosclerotic cardiovascular diseases.

Modern Challenges in Type 2 Diabetes: Balancing New Medications with Multifactorial Care.

Caturano A, Galiero R, Rocco M, Tagliaferri G, Piacevole A, Nilo D, Di Lorenzo G, Sardu C, Vetrano E, Monda M, Marfella R, Rinaldi L, Sasso FC

Biomedicines · 7 Sept 2024

Type 2 diabetes mellitus (T2DM) is a prevalent chronic metabolic disorder characterized by insulin resistance and progressive beta cell dysfunction, presenting substantial global health and economic challenges. This review explores recent advancements in diabetes management, emphasizing novel pharmacological therapies and their physiological mechanisms.

Pharmacological Treatment of Binge Eating Disorder and Frequent Comorbid Diseases.

Himmerich H, Bentley J, McElroy SL

CNS drugs · 1 Sept 2024

Binge eating disorder (BED) is the most common specific eating disorder (ED). It is frequently associated with attention deficit hyperactivity disorder (ADHD), depression, bipolar disorder (BD), anxiety disorders, alcohol and nicotine use disorder, and obesity. The aim of this narrative review was to summarize the evidence for the pharmacological treatment of BED and its comorbid disorders.

Structural insights into the triple agonism at GLP-1R, GIPR and GCGR manifested by retatrutide.

Li W, Zhou Q, Cong Z, Yuan Q, Li W, Zhao F, Xu HE, Zhao LH, Yang D, Wang MW

Cell discovery · 17 Jul 2024

Abstract not reported

Triple hormone receptor agonist retatrutide for metabolic dysfunction-associated steatotic liver disease: a randomized phase 2a trial.

Sanyal AJ, Kaplan LM, Frias JP, Brouwers B, Wu Q, Thomas MK, Harris C, Schloot NC, Du Y, Mather KJ, Haupt A, Hartman ML

Nature medicine · 1 Jul 2024

Retatrutide is a novel triple agonist of the glucose-dependent insulinotropic polypeptide, glucagon-like peptide 1 and glucagon receptors. A 48-week phase 2 obesity study demonstrated weight reductions of 22.8% and 24.2% with retatrutide 8 and 12 mg, respectively.

Gut hormones and appetite regulation.

Hong SH, Choi KM

Current opinion in endocrinology, diabetes, and obesity · 1 Jun 2024

PURPOSE OF REVIEW: Various gut hormones interact with the brain through delicate communication, thereby influencing appetite and subsequent changes in body weight. This review summarizes the effects of gut hormones on appetite, with a focus on recent research.

Sex, race, and BMI in clinical trials of medications for obesity over the past three decades: a systematic review.

Alsaqaaby MS, Cooney S, le Roux CW, Pournaras DJ

The lancet. Diabetes & endocrinology · 1 Jun 2024

Medications for obesity have been studied in various populations over the past three decades. We aimed to quantify the baseline demographic characteristics of BMI, sex, age, and race in randomised clinical trials (RCTs) across three decades to establish whether the population studied is representative of the global population affected by the disease.

Oral glucagon-like peptide-1 receptor agonists and combinations of entero-pancreatic hormones as treatments for adults with type 2 diabetes: where are we now?

Gogineni P, Melson E, Papamargaritis D, Davies M

Expert opinion on pharmacotherapy · 1 May 2024

INTRODUCTION: Glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) have changed the landscape of type 2 diabetes (T2D) management due to their cardio-renal benefits, their glucose-lowering efficacy and weight loss (WL) maintenance. However, the response to GLP-1 RA monotherapy is heterogeneous. Additionally, the majority of GLP-1 RAs are injectable treatments.

Advancements in the management of obesity: a review of current evidence and emerging therapies.

Abdalla Ahmed MA, Ssemmondo E, Mark-Wagstaff C, Sathyapalan T

Expert review of endocrinology & metabolism · 1 May 2024

INTRODUCTION: Obesity is the modern world's current epidemic, with substantial health and economic impact. This study aimed to provide a narrative overview of the past, currently available, and future treatment options that offer therapeutic and preventive advantages for obesity management.

A review of an investigational drug retatrutide, a novel triple agonist agent for the treatment of obesity.

Kaur M, Misra S

European journal of clinical pharmacology · 1 May 2024

BACKGROUND: Obesity is one of the critical public health problems in our society. It leads to various health conditions, such as type 2 diabetes mellitus, cardiovascular disease, hypertension, dyslipidaemia, and non-alcoholic fatty liver disease. With the rising incidence of obesity, there is a growing demand for new therapies which can effectively manage body weight and improve health.

Top studies of 2023 relevant to primary care: From the PEER team.

Thomas BS, Perry D, Moe SS, Turgeon RD, Potter J, Braschi É, Dugré N, Kirkwood JEM, Allan GM

Canadian family physician Medecin de famille canadien · 1 Apr 2024

OBJECTIVE: To provide a summary of the noteworthy medical articles published in 2023 that are relevant to family physicians. SELECTING THE EVIDENCE: Articles were chosen and ranked by the PEER (Patients, Experience, Evidence, Research) team, a group of primary care health professionals focused on evidence-based medicine.

Rare genetic forms of obesity in childhood and adolescence: A narrative review of the main treatment options with a focus on innovative pharmacological therapies.

Mainieri F, La Bella S, Rinaldi M, Chiarelli F

European journal of pediatrics · 1 Apr 2024

The prevalence of obesity in children and adolescents is increasing, and it is recognised as a complex disorder that often begins in early childhood and persists throughout life. Both polygenic and monogenic obesity are influenced by a combination of genetic predisposition and environmental factors.

Recent advances in peptide-based therapies for obesity and type 2 diabetes.

Bailey CJ, Flatt PR, Conlon JM

Peptides · 1 Mar 2024

Options for the treatment of type 2 diabetes mellitus (T2DM) and obesity have recently been expanded by the results of several large clinical trials with incretin-based peptide therapies.

Review article: Pharmacologic management of obesity - updates on approved medications, indications and risks.

Lupianez-Merly C, Dilmaghani S, Vosoughi K, Camilleri M

Alimentary pharmacology & therapeutics · 1 Feb 2024

BACKGROUND: Obesity has reached epidemic proportions, with >40% of the US population affected. Although traditionally managed by lifestyle modification, and less frequently by bariatric therapies, there are significant pharmacological advancements.

Unleashing the power of retatrutide: A possible triumph over obesity and overweight: A correspondence.

Naeem M, Imran L, Banatwala UESS

Health science reports · 1 Feb 2024

BACKGROUND AND AIMS: Overweight and obesity have become global health challenges with increasing prevalence. Several drugs have received Food and Drug Administration approval for nonsyndromic obesity treatment, but most have limitations, including gastrointestinal side effects and limited weight loss efficacy.

Treatment of obesity with medications binding the glucagon-like peptide 1 receptor: what is the current state of play?

Le Roux C, Mondoh A

Expert opinion on pharmacotherapy · 1 Feb 2024

INTRODUCTION: Obesity, marked by abnormal fat accumulation, poses significant health risks, necessitating effective therapeutic interventions. The focus of this review is to elucidate the importance of glucagon-like peptide 1 (GLP-1) receptor-binding medications in addressing obesity-related health deteriorations.

The Road towards Triple Agonists: Glucagon-Like Peptide 1, Glucose-Dependent Insulinotropic Polypeptide and Glucagon Receptor - An Update.

Jakubowska A, Roux CWL, Viljoen A

Endocrinology and metabolism (Seoul, Korea) · 1 Feb 2024

Obesity is the fifth leading risk factor for global deaths with numbers continuing to increase worldwide. In the last 20 years, the emergence of pharmacological treatments for obesity based on gastrointestinal hormones has transformed the therapeutic landscape.

At ObesityWeek, More Data and Questions About Semaglutide, Tirzepatide, and Retatrutide.

Ruder K

JAMA · 2 Jan 2024

This Medical News article discusses weight-loss medications highlighted at ObesityWeek 2023.

Advancements in pharmacological treatment of NAFLD/MASLD: a focus on metabolic and liver-targeted interventions.

Ciardullo S, Muraca E, Vergani M, Invernizzi P, Perseghin G

Gastroenterology report · 1 Jan 2024

In the present narrative review, we have summarized evidence on the pharmacological treatment of non-alcoholic fatty liver disease (NAFLD)/metabolic dysfunction-associated steatotic liver disease (MASLD). We start by reviewing the epidemiology of the condition and its close association with obesity and type 2 diabetes.

Comparative Meta-Analysis of Retatrutide Versus Placebo and Dulaglutide for Weight Loss and Diabetes Management: Insights From Clinical Trials.

Ayesh H, Ayesh S, Niswender K

American journal of therapeutics · 1 Jan 2024

Abstract not reported

Retatrutide.

Ramsbacher N

Clinical diabetes : a publication of the American Diabetes Association · 1 Jan 2024

Abstract not reported

Approved and Emerging Hormone-Based Anti-Obesity Medications: A Review Article.

Sidrak WR, Kalra S, Kalhan A

Indian journal of endocrinology and metabolism · 1 Jan 2024

Obesity is a heterogeneous, complex, and chronic disease that has a detrimental impact on disability-adjusted life years across the globe. Recent advancements in our understanding of gut-brain communication at the molecular level have driven the development of next-generation anti-obesity medications (AOMs).

Future is Brighter: New Potential Paradigm-Shifting Medications and Regimens for Diabetes and Obesity.

Al-Horani RA, Aliter KF, Aliter HF

Current diabetes reviews · 1 Jan 2024

Diabetes is a chronic illness that can become debilitating owing to its microvascular and macrovascular complications. Its prevalence is increasing and so is its cost. Diabetes, particularly type 2, appears to have a very close relationship with obesity.

Triple-Hormone-Receptor Agonist Retatrutide for Obesity.

Bisson A, Fauchier G, Fauchier L

The New England journal of medicine · 26 Oct 2023

Abstract not reported

[From GLP1 receptor agonists to triple hormone receptor activation supplemented with glucagon receptor agonism.].

Winkler G, Kis JT, Arapovicsné Kiss K, Schandl L

Orvosi hetilap · 22 Oct 2023

Following the introduction of mono- and then dual hormone (incretin) receptor agonists into therapy, attention was turned to multiple receptor stimulation, with the additional activation of the glucagon receptor, as a new option for the pharmaceutical treatment of type 2 diabetes and obesity.

The novel GIP, GLP-1 and glucagon receptor agonist retatrutide delays gastric emptying.

Urva S, O'Farrell L, Du Y, Loh MT, Hemmingway A, Qu H, Alsina-Fernandez J, Haupt A, Milicevic Z, Coskun T

Diabetes, obesity & metabolism · 1 Sept 2023

Abstract not reported

Retatrutide, a GIP, GLP-1 and glucagon receptor agonist, for people with type 2 diabetes: a randomised, double-blind, placebo and active-controlled, parallel-group, phase 2 trial conducted in the USA.

Rosenstock J, Frias J, Jastreboff AM, Du Y, Lou J, Gurbuz S, Thomas MK, Hartman ML, Haupt A, Milicevic Z, Coskun T

Lancet (London, England) · 12 Aug 2023

BACKGROUND: According to current consensus guidelines for type 2 diabetes management, bodyweight management is as important as attaining glycaemic targets. Retatrutide, a single peptide with agonist activity at the glucose-dependent insulinotropic polypeptide (GIP), GLP-1, and glucagon receptors, showed clinically meaningful glucose-lowering and bodyweight-lowering efficacy in a phase 1 study.

Triple-Hormone-Receptor Agonist Retatrutide for Obesity - A Phase 2 Trial.

Jastreboff AM, Kaplan LM, Frías JP, Wu Q, Du Y, Gurbuz S, Coskun T, Haupt A, Milicevic Z, Hartman ML, Retatrutide Phase 2 Obesity Trial Investigators

The New England journal of medicine · 10 Aug 2023

BACKGROUND: Retatrutide (LY3437943) is an agonist of the glucose-dependent insulinotropic polypeptide, glucagon-like peptide 1, and glucagon receptors. Its dose-response relationships with respect to side effects, safety, and efficacy for the treatment of obesity are not known.

Triple-Hormone Combination Retatrutide Induces 24% Body Weight Loss.

Harris E

JAMA · 25 Jul 2023

Abstract not reported

Differentiation of human subcutaneous adipocytes and measurement of lipolytic function induced by GIP or LY3437943.

Regmi A, Roell W

STAR protocols · 16 Jun 2023

Human subcutaneous adipocytes are an attractive therapeutic target in regulating overall physiological homeostasis. However, the differentiation of primary human adipose-derived models remains challenging. Here, we present a protocol to differentiate primary subcutaneous adipose-derived preadipocytes from human subcutaneous adipocytes and to measure lipolytic activity.

Is retatrutide (LY3437943), a GLP-1, GIP, and glucagon receptor agonist a step forward in the treatment of diabetes and obesity?

Doggrell SA

Expert opinion on investigational drugs · 1 May 2023

INTRODUCTION: Despite there being a wide range of medicines available for the treatment of type 2 diabetes, the high rate of mortality suggests treatment needs to be improved. Only a few medicines have shown long-term effectiveness in obesity, and new medicines are urgently needed.

Enteroendocrine cell regulation of the gut-brain axis.

Barton JR, Londregan AK, Alexander TD, Entezari AA, Covarrubias M, Waldman SA

Frontiers in neuroscience · 1 Jan 2023

Enteroendocrine cells (EECs) are an essential interface between the gut and brain that communicate signals about nutrients, pain, and even information from our microbiome.

Retatrutide showing promise in obesity (and type 2 diabetes).

Doggrell SA

Expert opinion on investigational drugs · 1 Jan 2023

INTRODUCTION: Obesity is a major risk factor for cardiovascular disease, diabetes, osteoarthritis, and some cancers. Retatrutide stimulates Glucagon-like peptide 1 (GLP-1), Glucose-dependent insulinotropic polypeptide (GIP) receptors, and glucagon receptors, and is being developed for the treatment of obesity and type 2 diabetes.

Retatrutide: a triple incretin receptor agonist for obesity management.

Ray A

Expert opinion on investigational drugs · 1 Jan 2023

INTRODUCTION: Obesity treatment is evolving rapidly with the emergence of agents targeting incretin receptors. Retatrutide, a triple agonist of these receptors, shows promise in obesity management. AREAS COVERED: Retatrutide, in phase-2 trials, exhibited significant reductions in glycated hemoglobin (HbA1c) and dose-dependent weight loss in individuals with type 2 diabetes mellitus (T2DM).

LY3437943, a novel triple GIP, GLP-1, and glucagon receptor agonist in people with type 2 diabetes: a phase 1b, multicentre, double-blind, placebo-controlled, randomised, multiple-ascending dose trial.

Urva S, Coskun T, Loh MT, Du Y, Thomas MK, Gurbuz S, Haupt A, Benson CT, Hernandez-Illas M, D'Alessio DA, Milicevic Z

Lancet (London, England) · 26 Nov 2022

BACKGROUND: Treating hyperglycaemia and obesity in individuals with type 2 diabetes using multi-receptor agonists can improve short-term and long-term outcomes.

LY3437943, a novel triple glucagon, GIP, and GLP-1 receptor agonist for glycemic control and weight loss: From discovery to clinical proof of concept.

Coskun T, Urva S, Roell WC, Qu H, Loghin C, Moyers JS, O'Farrell LS, Briere DA, Sloop KW, Thomas MK, Pirro V, Wainscott DB, Willard FS, Abernathy M, Morford L, Du Y, Benson C, Gimeno RE, Haupt A, Milicevic Z

Cell metabolism · 6 Sept 2022

With an increasing prevalence of obesity, there is a need for new therapies to improve body weight management and metabolic health. Multireceptor agonists in development may provide approaches to fulfill this unmet medical need.