Mechanistic / preclinical researchPrimaryPMID 42385950DOI 10.1016/j.bbr.2026.116343
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. The present study investigated whether Retatruti…
Mechanistic / preclinical researchPrimaryPMID 42630988DOI 10.1016/j.isci.2026.117174
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. Integrating in vivo and in vitro data showed model- and drug-specific patterns …
Primary clinical researchSecondaryPMID 42682157DOI 10.23876/j.krcp.26.272
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. Glucagon-l…
Editorial / commentaryPrimaryPMID 42559975DOI 10.1111/dar.70231
Piatkowski T, Craven A, Cornell S, Ferris J
Drug and alcohol review · 1 Sept 2026
Abstract not reported
ReviewSecondaryPMID 42683980DOI 10.4103/ijp.ijp_37_26
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. Pharmacological the…
ReviewSecondaryPMID 42673585DOI 10.7326/ANNALS-25-05519
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.
DATA SOURCES: MEDLINE, Embase, and Cochrane Central Register of Controlled Trials from 5 October 2024 through 25 March…
ReviewSecondaryPMID 42556625DOI 10.1016/j.phrs.2026.108365
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. Currently FDA-ap…
OtherSecondaryPMID 42649514DOI 10.1186/s12933-026-03346-2
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. Building on the previously proposed "diabetes/diseas…
Primary clinical researchPrimaryPMID 42608321DOI 10.1111/dom.71200
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 · 17 Aug 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. In Study 1, adults with obesity/overweight and T2D …
OtherPrimaryPMID 42567543DOI 10.1136/bmj-2026-100530
Brown C
BMJ (Clinical research ed.) · 7 Aug 2026
Abstract not reported
Primary clinical researchSecondaryPMID 42562129DOI 10.1016/j.clindermatol.2026.07.030
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 (T2DM) and obesity, with increasing relevance to dermatologic practice as more patients present while receiving these therapies. This medication class now includes oral formulations including oral semaglutide and the first non-peptide oral GLP-1RA, orforglipron as well as nex…
ReviewSecondaryPMID 42590128DOI 10.3390/jcm15156026
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. These agents are now discussed in relation to longevity and aesthetic medicine, raising the question of whether …
ReviewSecondaryPMID 42208956DOI 10.1016/S2213-8587(26)00100-2
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. This Review synthesises evidence from randomised controlled trials and high-quality meta-analyses on approved and late-stage investigational obesity medications, including phentermine-…
Meta-analysisSecondaryPMID 42296503DOI 10.7326/ANNALS-24-03764
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.
DATA SOURCES: MEDLINE and Cochrane Central Register of Controlled Trials until October 2025…
Case reportPrimaryPMID 42669023DOI 10.7759/cureus.115260
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. Retatrutide is a novel triple agonis…
Mechanistic / preclinical researchPrimaryPMID 42527705DOI 10.1038/s41684-026-01778-7
Ferreira J
Lab animal · 1 Aug 2026
Abstract not reported
Editorial / commentaryPrimaryPMID 42493254DOI 10.1016/j.ejim.2026.107099
Koufakis T, Argyrakopoulou G, Kokkinos A, le Roux CW
European journal of internal medicine · 23 Jul 2026
Abstract not reported
OtherSecondaryPMID 42603384DOI 10.1016/j.chroma.2026.467288
Tong LH, Leung KK, Hung CT
Journal of chromatography. A · 21 Jul 2026
A rapid, sensitive, and selective multiplexed liquid chromatography-high-resolution mass spectrometry (LC-HRMS) method was developed and validated for the identification and quantitation of nine structurally diverse peptide-based glucagon-like peptide-1 receptor agonists (GLP-1 RAs): bofanglutide, ecnoglutide, exenatide, liraglutide, mazdutide, retatrutide, semaglutide, survodutide, and tirzepatid…
OtherSecondaryPMID 42444567DOI 10.1210/clinem/dgag274
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.
EVIDENCE ACQUISITION: A systematic literature search of th…
OtherPrimaryPMID 42425580DOI 10.1136/bmj-2026-100245
Mahase E
BMJ (Clinical research ed.) · 9 Jul 2026
Abstract not reported
Meta-analysisSecondaryPMID 42419792DOI 10.1136/bmj-2026-372161
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.
DESIGN: Systematic review and network meta-analysis of 24 outcomes using frequentist random effects models and bayesian dose-response models, the GRADE (Grading of Recommendations …
ReviewPrimaryPMID 42371360DOI 10.1007/s40292-026-00812-6
Simental-Mendía LE, Barragán-Zúñiga LJ, Reyes-Avitia V
High blood pressure & cardiovascular prevention : the official journal of the Italian Society of Hypertension · 29 Jun 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.
AIM: This meta-analysis aims to investigate the effect of retatrutide …
Clinical trial resultsPrimaryPMID 42250575DOI 10.1016/S0140-6736(26)00967-0
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.
METHODS: In this 40-week, phase 3, randomised, double-blind, p…
OtherPrimaryPMID 42224238DOI 10.1021/acs.orglett.6c02001
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). At present, its synthesis relies predominantly on solid-phase peptide synthesis (SPPS), an approach that suffers from inherent limitations in terms of efficiency, scalability, and structural flexibility…
OtherPrimaryPMID 42264536DOI 10.1136/bmj-2026-102036
Lang K
BMJ (Clinical research ed.) · 9 Jun 2026
Abstract not reported
ReviewSecondaryPMID 42249250DOI 10.1007/s13679-026-00722-7
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. This review outlines the neural mechanisms through which the central nervous system regulates appetite and the perip…
Mechanistic / preclinical researchSecondaryPMID 42219269DOI 10.1093/asj/sjag108
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. Howeve…
ReviewSecondaryPMID 41933725DOI 10.1016/j.clnesp.2026.103260
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. Childhood obesity significantly heightens the risk of adult obesity and cardiovascular diseases (CVD) …
Mechanistic / preclinical researchPrimaryPMID 41997446DOI 10.1016/j.molmet.2026.102365
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. It propelled the identification of a unimolecular GIPR:GCGR co-agonist lacking …
ReviewSecondaryPMID 42529769DOI 10.7759/cureus.111728
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. Dual and triple glucagon-like peptide-1 (GLP-1)-based polyagonists may provide complementary hepatic and metabolic benefits, but their overall efficac…
Mechanistic / preclinical researchPrimaryPMID 41741376DOI 10.1002/oby.70155
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. vehicle), both fat and lean mass, …
ReviewSecondaryPMID 41948476DOI 10.1016/j.metop.2026.100463
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. However, GLP-1-based therapies have revealed important limitations, including weight loss pl…
Clinical trial resultsPrimaryPMID 41160422DOI 10.1093/ndt/gfaf230
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. Mechanism-of-action studies are needed to unde…
ReviewSecondaryPMID 42168638DOI 10.1007/s00228-026-04079-7
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.
METHODS: We conducted a disproportionality analysis using Vigi…
Mechanistic / preclinical researchSecondaryPMID 42156758DOI 10.1038/s41467-026-72974-9
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. Mec…
ReviewSecondaryPMID 42198313DOI 10.3390/pharmaceutics18050620
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. Incretin-based therapies, including glucagon-like peptide-1 receptor agonists (GLP-1 RAs), as well as dual agonists like tirzepatide, have demonstrated significant cardiovascular bene…
ReviewSecondaryPMID 42195239DOI 10.3390/medicina62050986
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. In the absence of approved pharmacological treatments and due to its high risk of progression to advanced fibrosis, MASLD represents a sign…
Primary clinical researchPrimaryPMID 42135195DOI 10.1210/clinem/dgag201
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. Particip…
Primary clinical researchPrimaryPMID 42108533DOI 10.1097/CRD.0000000000001310
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. Phase 2 clinical …
Mechanistic / preclinical researchPrimaryPMID 40699363DOI 10.1007/s00213-025-06854-3
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. Glucagon-like peptide-1 (GLP-1) receptor agonists, originally developed for type 2 diabetes, have emerged as promising candidates due to effects on intake regulation and reward proc…
Mechanistic / preclinical researchPrimaryPMID 41964043DOI 10.1186/s13098-026-02116-0
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. METHODS: Using a high-fat diet–induced obesity mouse model, we investigated the effects of Retatrutide on adipose tissue through integrated physiological, histologica…
ReviewPrimaryPMID 41785010DOI 10.1080/17512433.2026.2642415
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. Retatrutide (LY3437943) is a novel triple agonist targeting glucagon receptor (GCGR), glucose-dependent insulinotropic polypeptide receptor (GIPR), and glucagon-like peptide-1 recep…
ReviewSecondaryPMID 42165732DOI 10.25259/IJMR_2041_2025
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). Literatu…
ReviewSecondaryPMID 41297910DOI 10.3350/cmh.2025.0744
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. Despite the significant benefits in glycemic control and weight loss exhibited by GLP-1 receptor agonists (GLP-1RAs), their limitations have initiated the developme…
Mechanistic / preclinical researchPrimaryPMID 41723268DOI 10.1038/s41366-026-02025-2
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. Recently, glucagon-li…
ReviewSecondaryPMID 41823054DOI 10.1111/liv.70576
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. The L-α-lysophosphatidylinositol/G protein-coupled receptor 55 (LPI/GPR55) axis, an element of the endocannabinoidome, has emerged as a key driver behind liver disease progression, leading…
ReviewSecondaryPMID 41831086DOI 10.1007/s11892-026-01621-w
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. RECENT FINDINGS: Among glucose-lowering therapies, GLP-1 RAs, dual GIP/GLP-1 RAs, pioglitazo…
ReviewSecondaryPMID 41054801DOI 10.1210/endrev/bnaf036
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. These next-generation agents engage not only GLP-1 receptors but also those for other gastro-entero-pancreatic hormones such as glucose-dependent insulinotropic polypeptide (G…
ReviewSecondaryPMID 41547240DOI 10.1016/j.ejmech.2026.118587
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. Drugs like tirzepatide and retatrutide have shown unprecede…
ReviewSecondaryPMID 40755350DOI 10.14670/HH-18-967
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). Glucagon-like peptide-1 (GLP-1) has been a primary focus in this field, leading to the development of…
Meta-analysisPrimaryPMID 41787737DOI 10.1002/edm2.70187
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. This comprehensive meta-analysis evalu…
Primary clinical researchSecondaryPMID 41711462DOI 10.1097/CRD.0000000000001209
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. A comprehensive literature search was conducted using PubMed, the Co…
Primary clinical researchSecondaryPMID 41589220DOI 10.1002/osp4.70119
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. The Weight and Emotions Scale (WES) was developed to enable robust evaluation of the impact of obesity or overweight and the benefits of treatment on pa…
ReviewSecondaryPMID 41582189DOI 10.1186/s40001-026-03933-9
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.
…
Primary clinical researchSecondaryPMID 41540866DOI 10.53738/REVMED.2026.22.945.47996
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. A double dose of icodextrin did not reduce mortality, peritonitis, or hospitalizatio…
Primary clinical researchSecondaryPMID 42688617DOI 10.1136/bmjmed-2026-003026
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.
ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Randomised controlled tr…
Primary clinical researchSecondaryPMID 41201783DOI 10.1007/s12325-025-03386-2
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. Here we describe the development and content evaluation of the Eating Behavior …
ReviewSecondaryPMID 42318576DOI 10.2147/DMSO.S566414
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. This narrative review evaluates the mechanisms, clinical e…
Meta-analysisSecondaryPMID 42394981DOI 10.3389/fphar.2026.1846714
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.
METHODS: A systematic re…
ReviewSecondaryPMID 42602523DOI 10.3389/fendo.2026.1925534
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. Tirzepatide and retatrutide, the latest generation of GLP-1-incorporating multi-agonists, target multiple receptors in complementary systems to achieve ma…
ReviewSecondaryPMID 42568490DOI 10.3389/fendo.2026.1898812
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. This state-of-the-art review synthesizes the cardiovascular evidence base …
Primary clinical researchPrimaryPMID 40613938DOI 10.1007/s00210-025-04421-3
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. Retatrutide, a not endogenously occurring peptide, stimulated the glucagon receptor (GCGR), the glucose-dependent insulinotropic polypeptide (GIP) receptor (GIPR), and the glucagon-like peptide-1 receptor (GLP-1R) in cell cultures; increased the activity of adenylyl cyclases (AC); and thus augmented the 3',5' cyc…
ReviewSecondaryPMID 42037991DOI 10.3389/fphys.2026.1795058
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. Beyond excess energy storage, white adipose tissue (WAT) functions as an active endocrine and immune organ that, during obesity, undergoes inflammatory remodeling and releases cytokines, lipid mediators, adipokines, and extracellular vesicles that infl…
ReviewSecondaryPMID 42536830DOI 10.1051/jbio/2026005
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. A first step was achieved with the discove…
ReviewSecondaryPMID 41478576DOI 10.1016/j.phrs.2025.108077
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. While this current generation of incretin analogues show weight regain upon cessation of treatment, the amount of which can depend on the treatment and patient, iterative advancements may im…
Primary clinical researchPrimaryPMID 41090431DOI 10.1111/dom.70209
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). A novel basket tr…
ReviewPrimaryPMID 41545327DOI 10.1002/cpdd.70001
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. Retatrutide (LY3437943), a novel triple agonist targeting GLP-1, glucose-dependent insulinotropic polypeptide …
Mechanistic / preclinical researchPrimaryPMID 41056349DOI 10.1152/ajpgi.00164.2025
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. C57B…
ReviewPrimaryPMID 41537067DOI 10.26574/maedica.2025.20.4.824
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. This meta-analysis and systematic review sought to co…
Primary clinical researchPrimaryPMID 41216380DOI 10.1016/j.obpill.2025.100220
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.
METHODS: This was a qualitative exit interview study conducte…
ReviewSecondaryPMID 41025406DOI 10.1111/dom.70148
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. However, recent evidence has revealed other potential roles of glucagon, which include the regulation of amino acid metabolism via a liver-pancreatic alpha cell axis, stimulatio…
Mechanistic / preclinical researchPrimaryPMID 40464942DOI 10.1007/s00210-025-04335-0
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. We tested the hypothesis that retatrutide like the β-adrenoceptor agonist isoprenaline raises force of contraction (FOC) in isolated electrically drive…
Clinical trial resultsPrimaryPMID 40916752DOI 10.1111/dom.70097
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.
MATERIALS AND METHODS: These pre-specified exploratory analyses examined changes from baseline in Appetite Visual Analogue Scale (VAS) and Eati…
ReviewSecondaryPMID 41375628DOI 10.3390/jcm14238326
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. Current therapies encompass five classes of drugs: (1) angiotensin-converting-enzyme inhibitors (ACEI) or angiotensin II receptor blockers (AIIRB); (2) sodium-…
Meta-analysisSecondaryPMID 41303824DOI 10.3390/medicina61111987
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. Objective: To systematically evaluate the frequency, severity, and types of GI adverse effects (AEs) associated with anti-obesity med…
ReviewSecondaryPMID 40865172DOI 10.1016/j.medcli.2025.107152
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. Beyond the necessary lifestyle changes, …
ReviewPrimaryPMID 40583149DOI 10.1111/acem.70088
Olowo-Oribi BA, Salway RJ
Academic emergency medicine : official journal of the Society for Academic Emergency Medicine · 1 Nov 2025
Abstract not reported
ReviewSecondaryPMID 41393574DOI 10.7759/cureus.96739
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. We summarize mechanisms of action, pivotal efficacy data, safety profiles, indications, prescribing guida…
Meta-analysisPrimaryPMID 40685589DOI 10.1002/oby.24360
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.
METHODS: We conducted a systematic review and Bayesian network meta-analysis (NMA) of 19 randomized controlled trials (RCTs) including 29,506 adults (BMI ≥ 25 kg/m2…
OtherSecondaryPMID 40958513DOI 10.1021/acs.jmedchem.5c02032
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. Using sequence analysis, molecular dynamics simulations, docking, and amino…
ReviewSecondaryPMID 41025003DOI 10.3748/wjg.v31.i37.111435
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. The use of anti-obesity medications (AOMs) in this population is complex du…
Clinical trial resultsPrimaryPMID 40726454DOI 10.1111/dom.16661
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
AIMS: The aim of this study was to determine if retatrutide, a triple agonist of glucose-dependent insulinotropic polypeptide (GIP) receptor, glucagon-like peptide 1 (GLP-1) receptor and glucagon (GCG) receptor, may lower serum triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C) levels in part by decreasing circulating concentrations of the angiopoietin-like protein 3/8 complex (ANGP…
Editorial / commentaryPrimaryPMID 40735804DOI 10.1111/dom.16662
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
Meta-analysisSecondaryPMID 40489581DOI 10.1210/clinem/dgaf336
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.
METHODS: We searched PubMed, Embase, and Cochr…
ReviewSecondaryPMID 40980310DOI 10.4239/wjd.v16.i9.109123
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. This weight loss can be achieved through pharmacotherapy, including glucagon-like peptide 1 (GLP-1) receptor agonists, GLP-1/glucose-dependent insu…
ReviewSecondaryPMID 40728225DOI 10.23736/S0031-0808.25.05339-X
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%. Having understood better the role of the gut-brain axis on appetite…
ReviewSecondaryPMID 41141001DOI 10.7759/cureus.93104
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. Research has explored the use of newly developed incretin mimetics as standard therapy for insulin resistance in insulin-dependent tissues associated …
Meta-analysisSecondaryPMID 40988099DOI 10.1002/edm2.70113
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).
METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), a systematic search was performed in PubMed, Embase, and Cochrane Library for GLP-1 RA RCTs that evaluated pancreatitis/…
Meta-analysisSecondaryPMID 40471293DOI 10.1007/s00592-025-02534-y
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.
PURPOSE: This systematic review and network meta-analysis uniquely evaluates the efficacy and safety of dual and triple incretin agon…
ReviewSecondaryPMID 40949933DOI 10.4330/wjc.v17.i8.107991
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. The GLP-1 receptor agonists (GLP-1RAs), namely liraglutide, dulaglut…
Clinical trial resultsPrimaryPMID 40609566DOI 10.1016/S2213-8587(25)00092-0
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.
METHODS: This phase 2, double-blind, parallel-group, pla…
ReviewSecondaryPMID 40843857DOI 10.3390/medicines12030019
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). Despite …
ReviewSecondaryPMID 40554267DOI 10.1016/j.pharmr.2025.100058
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. This review summarizes the development and mode of action and available published data on the effectiveness of approved…
Meta-analysisPrimaryPMID 40728138DOI 10.1515/jbcpp-2025-0113
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. We conducted a com…
Primary clinical researchPrimaryPMID 40630318DOI 10.1016/j.ekir.2025.03.049
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.
METHODS: A post hoc analysis of 2 retatrutide studies (dose range: 0.5-12 mg) was performed in participants (es…
Meta-analysisSecondaryPMID 39911047DOI 10.1089/dia.2024.0533
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. A total of 137 trials, encompassing 310 treatment…
ReviewPrimaryPMID 40563436DOI 10.3390/biom15060796
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. This review synthesizes findings from preclinica…
ReviewSecondaryPMID 40081498DOI 10.1016/j.peptides.2025.171380
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). Randomised clinical trials and 'real-world' studies have confirmed the marked glucose-lowering and weight-lowering efficacy of these age…
ReviewSecondaryPMID 40042613DOI 10.1007/s00115-025-01813-x
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. The GLP‑1 receptor agonists increase insulin rel…
Meta-analysisSecondaryPMID 40207414DOI 10.1111/1753-0407.70082
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.
METHODS: A meta-analysis was conducted using PubMed, Embase, Cochrane, and Web of Science databases …
ReviewSecondaryPMID 40126003DOI 10.20452/pamw.16983
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. Pharmacological approaches …
Primary clinical researchSecondaryPMID 39980735DOI 10.1016/j.obpill.2025.100162
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. This study compared the efficacy and safety profiles of different GLP-1 receptor a…
Mechanistic / preclinical researchPrimaryPMID 39868848DOI 10.1002/advs.202407494
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. Through multiomic analysis and experimental validation, a dysfunctional Eukaryotic Translation Initiation Factor 3 Subunit H (EIF3H)/Yes-associated protein (YAP) proteolytic axis is identified as a pivotal junction mediating the interplay bet…
ReviewSecondaryPMID 40206909DOI 10.7759/cureus.80321
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. This literature review evaluates and compares the effectiveness of four pharmacological agents semaglutide, liraglutide, orlistat, phentermine, and emerging agents like setmelanotide, amy…
ReviewSecondaryPMID 40022548DOI 10.1080/13543784.2025.2472408
Madsbad S, Holst JJ
Expert opinion on investigational drugs · 1 Mar 2025
INTRODUCTION: GLP-1-based therapies have changed the treatment of overweight/obesity. Liraglutide 3.0 mg daily, the first GLP-1 RA approved for treatment of overweight, induced a weight loss of 6-8%, Semaglutide 2.4 mg once weekly improved weight loss to about 12-15%, while the dual GIP/GLP-1 receptor agonist tirzepatide once weekly has induced a weight loss of about 20% in obese peo…
ReviewSecondaryPMID 38302593DOI 10.1038/s41366-024-01473-y
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). Semaglutide 2.4 …
Meta-analysisSecondaryPMID 40040445DOI 10.1111/1753-0407.70063
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. Subgroup analyses were stratified by individual GLP-1RA medications, dose, treatment du…
Meta-analysisSecondaryPMID 39761578DOI 10.7326/ANNALS-24-01590
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.
DATA SOURCES: MEDLINE, Embase,…
ReviewSecondaryPMID 39259982DOI 10.1146/annurev-pharmtox-061324-011832
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. Blockbuster drugs such as tirzepatide and retatrutide have shown unprecedented success in…
ReviewSecondaryPMID 41333115DOI 10.1155/jobe/9919810
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. These drugs not only provide unprecedented efficacy and acceptable safety in weight redu…
ReviewSecondaryPMID 40734920DOI 10.7573/dic.2025-4-8
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. Agents like mazdutide, pemvidutide, survodutide and retatrutide have demonstrated the ability to trigger significant…
Meta-analysisSecondaryPMID 39968298DOI 10.3389/fendo.2025.1513641
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.
MET…
ReviewPrimaryPMID 40741227DOI 10.1007/s12170-025-00770-z
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. Among these, triple agonists targeting GLP-1, GIP, and glucagon receptors rep…
ReviewPrimaryPMID 40291085DOI 10.1080/08998280.2025.2456441
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. Eligible studies comprise…
Mechanistic / preclinical researchPrimaryPMID 40094000DOI 10.1038/s44324-025-00054-5
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. We report that in pre-clinical models with significant retatrutide (RETA, LY3437943)-induced weight loss, pancreatic cancer engraftment was reduced, tumor onset was delayed, and progression was attenuated resulting in a 14-fold reduction in tumor volume compared to on…
Meta-analysisSecondaryPMID 39952695DOI 10.1124/pharmrev.123.001045
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. This systematic review of phase 2 and phase 3 trials in adults with overweight/obesity inv…
OtherSecondaryPMID 39776466DOI 10.1080/20523211.2024.2441220
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. We conducted a pilot study to assess the prevalence, characteristics, and advertising content of direct-to-consumer providers of compounded glucagon-like peptide-1 p…
Mechanistic / preclinical researchPrimaryPMID 39212900DOI 10.1007/s12020-024-03998-8
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. Subsequently, we assessed the effectiveness of these three drugs in controllin…
Meta-analysisPrimaryPMID 39817343DOI 10.1080/17512433.2025.2450254
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.
MATERIAL AND METHODS: A literature search was conducted in PubMed, Cochrane Central and Embase usi…
ReviewPrimaryPMID 39515565DOI 10.1016/j.ejphar.2024.177095
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. Retatrutide's complex mechanism of action involves a …
Primary clinical researchPrimaryPMID 39507873DOI 10.1177/87551225241285326
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. A literature review from April 2019 to April 2024 included such terms as "retatrutide," "LY3437943," "overweight," and "obesity." Phase I proof-of-concept studies led to phase II trials showing up to 24% body weight reduction an…
ReviewPrimaryPMID 39318607DOI 10.1016/j.metop.2024.100321
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).
METHODS: PubMed, Embase, Cochrane Library, and ClinicalTrials.gov databases were systematically searched for placebo-controlled, randomized clinical trials (RCTs) published up until February 23, 202…
ReviewSecondaryPMID 39726721DOI 10.1016/j.lanepe.2024.101098
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. The sequential conceptual developments of long-acting GLP-1 receptor (GLP-1R) mono-agonists, GLP-1R/glucose-depende…
Meta-analysisPrimaryPMID 39305981DOI 10.1016/j.metabol.2024.156038
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.
METHODS: Relevant randomized controlled trials (RCTs) with an intervention duration of at least 16 weeks assessing seven GLP-1…
ReviewSecondaryPMID 40604322DOI 10.1038/s44324-024-00030-5
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]). Lifestyle interventions represe…
ReviewSecondaryPMID 38843460DOI 10.2337/dci24-0003
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. In ongoing trials investigators are interrogating the efficacy of these agents for new indications, including metabolic liver disease, peripheral artery disease, Parkinson disease, and Alzheimer d…
Primary clinical researchPrimaryPMID 39724554DOI 10.1097/CRD.0000000000000793
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. Lifestyle modifications, such as diet and exercise, typically lead to approximately 3-5% weight loss, whereas 5-15% weight loss is necessary to significantly impact obesity-associated comorbidities and improve overall health outcomes…
ReviewSecondaryPMID 39458963DOI 10.3390/ph17101322
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. Material and Methods The inclusion criteria were (i) original full-text articles that are randomized control or clinical trials; (ii) published within the la…
ReviewSecondaryPMID 38471571DOI 10.1055/a-2266-1503
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. Obesity is a well-known risk factor for NAFLD, and both of them can markedly increase the odds of atherosclerotic cardiovas…
ReviewSecondaryPMID 38687506DOI 10.2337/dci23-0100
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. Glucagon-like peptide 1 receptor agonists (GLP-1RA) induce substantial weight loss in randomized trials, effects that may be enhanced in combination with glucose-dependen…
ReviewSecondaryPMID 39335551DOI 10.3390/biomedicines12092039
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. We highlight the transformative impact of So…
ReviewSecondaryPMID 39096466DOI 10.1007/s40263-024-01111-1
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. We rec…
Editorial / commentaryPrimaryPMID 39019866DOI 10.1038/s41421-024-00700-0
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
Clinical trial resultsPrimaryPMID 38858523DOI 10.1038/s41591-024-03018-2
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. The primary objective of this substudy was to assess mean relative change from baseline in liver fat (LF) at 24 weeks in …
ReviewSecondaryPMID 38511400DOI 10.1097/MED.0000000000000859
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.
RECENT FINDINGS: Ghrelin is known as an orexigenic hormone, whereas glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic poly…
Meta-analysisSecondaryPMID 38723646DOI 10.1016/S2213-8587(24)00098-6
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. Clinical trials of 12 medications for obesity (…
ReviewPrimaryPMID 38367045DOI 10.1007/s00228-024-03646-0
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.
CURRENT E…
ReviewSecondaryPMID 38753454DOI 10.1080/14656566.2024.2356254
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. Oral GLP-1 RAs and injectable comb…
ReviewSecondaryPMID 38685693DOI 10.1080/17446651.2024.2347258
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.
AREAS COVERED: Historically, rimonabant, and lorcaserin, were approved and used for managing non-syndromic …
ReviewSecondaryPMID 38227053DOI 10.1007/s00431-024-05427-4
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. Rare genetic obesity forms are caused by specific pathogenic variants in single genes that have a s…
ReviewSecondaryPMID 38626998DOI 10.46747/cfp.7004245
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. The selection process involved routine surveillance of tables of contents in…
Primary clinical researchSecondaryPMID 38184193DOI 10.1016/j.peptides.2024.171149
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. Most of these studies have been conducted with the glucagon-like peptide-1 (GLP-1) receptor agonist semaglutide, which is available as a once weekly subcutaneous injection and once daily tablet, and the once week…
ReviewSecondaryPMID 38356208DOI 10.3803/EnM.2024.1942
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. The successful development of glucagon-like peptide-1 (GLP-1) receptor agonists, followed by the synergistic combined effect of glucose-de…
Primary clinical researchPrimaryPMID 38323122DOI 10.1002/hsr2.1864
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.
BODY: Retatrutide, a novel incretin mimetic agent, has shown promise in clinical trials…
ReviewSecondaryPMID 38299476DOI 10.1080/14656566.2024.2311731
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.
AREAS COVERED: Exploring the mechanisms, efficacy, and safety profiles, this review…
ReviewSecondaryPMID 38169126DOI 10.1111/apt.17856
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.
AIMS: To conduct a narrative review of the neurohormonal and physiological understanding of weight gain and obesity, and the development, clinical tes…
OtherPrimaryPMID 38055301DOI 10.1001/jama.2023.23141
Ruder K
JAMA · 2 Jan 2024
This Medical News article discusses weight-loss medications highlighted at ObesityWeek 2023.
Meta-analysisPrimaryPMID 38976545DOI 10.1097/MJT.0000000000001743
Ayesh H, Ayesh S, Niswender K
American journal of therapeutics · 1 Jan 2024
Abstract not reported
OtherPrimaryPMID 39429457DOI 10.2337/cd24-0062
Ramsbacher N
Clinical diabetes : a publication of the American Diabetes Association · 1 Jan 2024
Abstract not reported
ReviewSecondaryPMID 38681750DOI 10.1093/gastro/goae029
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. We then discuss how randomized-controlled trials are performed following guidan…
ReviewSecondaryPMID 39676791DOI 10.4103/ijem.ijem_442_23
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). Glucagon-like peptide-1 receptor agonists (GLP1RAs) remain the front-runners in this rapid…
ReviewSecondaryPMID 38275036DOI 10.2174/0115733998276832231124170324
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. While lifestyle modifications, exercises, and current therapeutics have substantially improved clinical outcomes, the need for new therapeutics a…
Editorial / commentaryPrimaryPMID 37888927DOI 10.1056/NEJMc2310645
Jastreboff AM, Kaplan LM, Hartman ML
The New England journal of medicine · 26 Oct 2023
Abstract not reported
ReviewSecondaryPMID 37865924DOI 10.1556/650.2023.32894
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. In addition to its role in carbohydrate metabolism, the article reviews the other important physiological …
OtherPrimaryPMID 37311727DOI 10.1111/dom.15167
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
Clinical trial resultsPrimaryPMID 37385280DOI 10.1016/S0140-6736(23)01053-X
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. We …
Clinical trial resultsPrimaryPMID 37366315DOI 10.1056/NEJMoa2301972
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.
METHODS: We conducted a phase 2, double-blind, randomized, placebo-controlled trial involving adults who had a body-mass…
OtherPrimaryPMID 37405802DOI 10.1001/jama.2023.12055
Harris E
JAMA · 25 Jul 2023
Abstract not reported
OtherPrimaryPMID 37178114DOI 10.1016/j.xpro.2023.102304
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. We describe steps for seedin…
OtherPrimaryPMID 37086147DOI 10.1080/13543784.2023.2206560
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.
AREAS COVERED: A multiple-ascending dose phase 1b clinical trial of a new drug retatrutide (LY3437943), which in add…
OtherPrimaryPMID 37902090DOI 10.1080/13543784.2023.2276754
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). In non…
ReviewPrimaryPMID 37947489DOI 10.1080/13543784.2023.2283020
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.
AREAS COVERED: A phase 2 clinical trial of retatrutide (LY3437943) …
ReviewSecondaryPMID 38027512DOI 10.3389/fnins.2023.1272955
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. EECs are hormone-producing cells expressed throughout the gastrointestinal epithelium and have been leveraged by pharmaceuticals like semaglutide (Ozempic, Wegovy), terzepatide (Mounjaro), and retatrutide (Phase 2) for diabetes …
Clinical trial resultsPrimaryPMID 36354040DOI 10.1016/S0140-6736(22)02033-5
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 is a single peptide with agonist activity for glucagon, glucose-dependent insulinotropic polypeptide (GIP), and glucagon-like peptide 1 (GLP-1) receptors that is currently in development for the treatment of type 2 diabetes and f…
Mechanistic / preclinical researchPrimaryPMID 35985340DOI 10.1016/j.cmet.2022.07.013
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. LY3437943 is a novel triple agonist peptide at the glucagon receptor (GCGR), glucose-dependent insulinotropic polypeptide receptor (GIPR), and glucagon-like peptide-1 rece…