retatrutide (LY3437943) / Eli Lilly - LARVOL DELTA

Three Doses of Once Weekly Retatrutide in Adults with Knee Osteoarthritis and Obesity: An 80-Week, Phase 3 Randomized Clinical Trial (ACR Convergence 2026) - No abstract available

Clinical • P3 data • Genetic Disorders • Immunology • Obesity • Osteoarthritis • Rheumatology

Retatrutide Once Weekly for the Treatment of Knee Osteoarthritis Pain and Obesity: Results From a 68-Week Phase 3 Randomized Clinical Trial (ACR Convergence 2026) - No abstract available

Clinical • P3 data • Genetic Disorders • Immunology • Musculoskeletal Pain • Obesity • Osteoarthritis • Pain • Rheumatology

Advances in the management of obesity: non-pharmacological strategies, herbal formulations, current pharmacotherapy, emerging drugs, and future perspectives. (PubMed, Front Endocrinol (Lausanne)) - "This review provides the current understanding of obesity pharmacotherapy, discusses approved anti-obesity medications, highlights emerging therapeutic agents and drugs under clinical development, and explores future perspectives in obesity management. Additionally, the review addresses current challenges, safety concerns, and public health strategies required to combat the growing obesity epidemic."

Journal • Review • Cardiovascular • Genetic Disorders • Obesity

Future GLP-1 receptor co-agonists and their cardiac effects. (PubMed, Naunyn Schmiedebergs Arch Pharmacol) - "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...We discuss here the known (for tirzepatide and retatrutide) or predicted contractile effects of such co-agonists on isolated cardiac preparations of experimental animals, mainly in mice and compare these results with data in isolated human cardiac preparations...We will discuss not only receptor agonists but also a receptor antagonist (AMG133). We identify research needs and controversies in the literature. We make suggestions for further preclinical research and what improvements in drug design for treatment may lie ahead."

Journal • Cardiovascular • Congestive Heart Failure • Coronary Artery Disease • Diabetes • Genetic Disorders • Heart Failure • Metabolic Disorders • Myocardial Infarction • Obesity • Type 2 Diabetes Mellitus

Comparative Efficacy and Safety of Incretin-Based Therapies, FGF21 Analogs, and Pan-PPAR Agonists for MASH: A Systematic Review and Bayesian Network Meta-Analysis (ACG 2026) - "Introduction: Metabolic dysfunctionâassociated steatohepatitis (MASH) is an increasing global health burden with limited approved therapies... A total of 14 RCT's comprising 8,462 patients were included, with 53.1% males and 46.9% females. Patients received semaglutide (n=1,642), tirzepatide (n=1,128), survodutide (n=612), retatrutide (n=318), efruxifermin (n=742), pegozafermin (n=512), lanifibranor (n=247), resmetirom (n=2,955), or placebo/standard therapy (n=306). Baseline age, BMI, diabetes prevalence, ALT, and fibrosis stages were comparable."

Retrospective data • Review • Diabetes • Fibrosis • Hepatology • Immunology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • FGF21

Select Lilly Presentations at EASD 2026 (PRNewswire) - "TRIUMPH-2: Adults with obesity or overweight and type 2 diabetes taking retatrutide lost up to an average of 49.6 lbs (22.5 kg; 20.8%) and lowered their A1C by up to an average of 1.6% at 80 weeks...This EASD-sponsored symposium on amylins in diabetes will feature Phase 2 results for eloraTZP, an investigational combination of eloralintide and tirzepatide, in adults with obesity or overweight and type 2 diabetes....ACHIEVE-4: Foundayo demonstrated non-inferiority versus insulin glargine, with a 16% lower risk of MACE-4 events (HR: 0.84; 95.0% CI: 0.59 to 1.20) and a 23% lower risk of MACE-3 events (HR: 0.77 95.0% CI: 0.52 to 1.13), in adults with type 2 diabetes and obesity or overweight at increased cardiovascular risk."

P2 data • P3 data • Obesity • Type 2 Diabetes Mellitus

Dangers of Injectable Peptides and Other Unregulated "Biohacking" Drugs. (PubMed, Mo Med) - "These unregulated substances-including the veterinary anabolic steroid trenbolone, investigational triple-agonists like retatrutide, and unapproved peptides such as BPC-157, TB-500, and melanotan-II-lack established human safety profiles. This review differentiates evidence-based therapeutics from unproven, high-risk compounds and outlines the molecular mechanisms of toxicity associated with popular "looksmaxxing" injectables. Clinicians must recognize these trends, and counsel patients on potential long-term health hazards of these potent agents."

Journal • Review • Cardiovascular • Oncology

Sustained weight loss exceeding 100 kg with sequential incretin-based therapy in Prader-Willi syndrome. (PubMed, JCEM Case Rep) - "He received sequential incretin-based therapy, initiated with retatrutide (1-12 mg weekly) within a clinical trial, followed by oral semaglutide and then dulaglutide after retatrutide became unavailable, together with a structured hypocaloric diet and supervised exercise. Mild transient gastrointestinal symptoms occurred during dose escalation, with no serious adverse events. Follow-up bioimpedance showed a skeletal muscle mass of 38.5 kg after a 58.8% reduction in total body weight."

Journal • Diabetes • Endocrine Disorders • Genetic Disorders • Metabolic Disorders • Obesity • Prader–Willi syndrome • Type 2 Diabetes Mellitus

Cagrilintide and retatrutide combination therapy enhances weight loss and metabolic outcomes in obese male rats. (PubMed, Nat Metab) - "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...Daily co-administration produces dose-dependent reductions in body weight and food intake that exceed both equimolar monotherapies and matched-dose comparator combinations incorporating semaglutide or tirzepatide...Plasma proteomic profiling highlights enrichment of bioenergetic processes with the combination therapy, whereas brain transcriptomic profiling identifies convergent central neuronal programmes linked to energy balance regulation. Collectively, our preclinical findings support five-receptor polypharmacology as a strategy for efficaciously lowering body weight and provide guidance for the design of next-generation unimolecular multi-receptor agonists."

Journal • Preclinical • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus • CALCR

Detection and Excretion Profile of Retatrutide in Human Plasma and Urine by LC-HRMS: Implications for Antidoping Analysis. (PubMed, Rapid Commun Mass Spectrom) - "These findings suggest that plasma represents the appropriate matrix for intact retatrutide detection compared with urine. The extended plasma detection window, approximately 56 days after the first dose, supports plasma-based testing as a suitable analytical strategy for this and related long-acting therapeutic peptides in antidoping testing context."

Journal

A frequentist network meta-analysis of bariatric surgery versus next-generation injectable and oral incretins for cardiometabolic disease (EASD 2026) - "Materials and A frequentist network meta-analysis was conducted synthesizing data from surgical RCTs (Roux-en-Y Gastric Bypass [RYGB], Sleeve Gastrectomy [SG]) and Phase 2/3 trials of advanced pharmacotherapies (tirzepatide, retatrutide, survodutide, CagriSema, and orforglipron)... When pooling estimates across broad metabolic populations, next-generation incretins successfully bridge the placebo- adjusted efficacy gap to bariatric surgery. The most potent injectable multi-agonists match the absolute mass offloading of sleeve gastrectomy, while accessible daily oral small molecules rival legacy surgical banding."

Bariatric surgery • Retrospective data • Surgery • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Pharmacological management of obesity: Current landscape and emerging therapies. (PubMed, Indian J Pharmacol) - "Currently, six medications (Orlistat, Phentermine/Topiramate, Naltrexone/Bupropion, Liraglutide, Semaglutide, and Tirzepatide) are approved by the U.S. Food and Drug Administration for long-term obesity management and among these, glucagon-like peptide receptor agonists have revolutionized the therapy...It has new dual and triple combinations such as CagriSema, Survodutide, and Retatrutide for better efficacy and metabolic outcomes, as well as long-acting and oral formulations, which will improve adherence and accessibility. India released its new obesity guideline in January 2025, emphasizing on early pharmacotherapy initiation and the adoption of stage-based obesity classification. Together, these developments signify a transformative era in obesity care where pharmacotherapy is a powerful and evidence-based tool that, in many cases, approaches the efficacy and metabolic benefits traditionally associated with bariatric surgeries."

Journal • Review • Cardiovascular • CNS Disorders • Diabetes • Genetic Disorders • Hepatology • Metabolic Disorders • Obesity • Psychiatry • Type 2 Diabetes Mellitus

Efficacy and Safety of Glucagon-like Peptide-1 Receptor Agonists and Co-agonists for Weight Loss Among Adults Without Diabetes : An Updated Systematic Review. (PubMed, Ann Intern Med) - "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...Among commercially available therapies, placebo-subtracted weight loss reached up to -5.8% (95% CI, -8.0% to -3.6%) for liraglutide, -14.8% (CI, -16.2% to -13.4%) for subcutaneous semaglutide, -14.3% (CI, -17.2% to -11.4%) for oral semaglutide, -12.4% (CI, -15.1% to -9.7%) for orforglipron, and -19.0% (CI, -21.6% to -16.4%) for tirzepatide. Numerically greater placebo-subtracted reductions were seen with emerging multiagonists, including -23.9% (CI, -29.3% to -18.5%) with amycretin and -22.1% (CI, -24.9% to -19.3%) with retatrutide...Head-to-head data showed greater weight loss with semaglutide and JNJ-64565111 than liraglutide and greater weight loss with tirzepatide and cagrilintide-semaglutide (CagriSema; Novo Nordisk) than semaglutide...None. (PROSPERO: CRD42024505558)."

Journal • Review • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity

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. (PubMed, BMJ Med) - "Compared with placebo, weight loss was greatest with retatrutide (-22.10%, 95% confidence interval -25.60% to -18.60%), followed by tirzepatide (-19.28%, -20.39% to -18.16%), and CagriSema (a combination of cagrilintide and semaglutide, -17.32%, -19.32% to -15.32%)...Low certainty evidence suggested higher rates for discontinuing treatment with danuglipron and retatrutide, whereas mazdutide showed better tolerability...Differences in tolerability, limited head-to-head evidence, and residual uncertainty, however, should be considered when interpreting comparative treatment effects. PROSPERO CRD420261279841."

Journal • Retrospective data • Diabetes • Endocrine Disorders • Genetic Disorders • Metabolic Disorders • Obesity

Retatrutide in Knee Osteoarthritis: Effects on Pain and Functional Outcomes (OBESITY WEEK 2026) - No abstract available

Immunology • Osteoarthritis • Pain • Rheumatology

Participant Experiences with Retatrutide for Weight Management in the TRIUMPH-1 Study (OBESITY WEEK 2026) - No abstract available

Semaglutide, Tirzepatide and Retatrutide Promote Metabolic Benefits in Obese Hamsters (OBESITY WEEK 2026) - No abstract available

Obesity

A Quintuple GLP-1R/GIPR/GCGR/AMYR/CALCR Agonist Drives Greater Weight Loss Than Retatrutide in Rats (OBESITY WEEK 2026) - No abstract available

Preclinical • CALCR

DA-1726 Demonstrates Comparable Weight Loss and Distinct Metabolic Profile Compared With Retatrutide (OBESITY WEEK 2026) - No abstract available

Metabolic Disorders

Obstructive sleep apnea, GLP-1 receptor agonist pharmacotherapy, and the oral microbiome: competing biological influences and implications for oral health monitoring. (PubMed, Clin Oral Investig) - "GLP-1RA pharmacotherapy in OSA creates a biologically complex oral microbiome environment whose clinical trajectory cannot be predicted from current evidence. Prospective studies are warranted, oral health monitoring beginning at treatment initiation is scientifically justified, and seven priority research questions are identified at the convergence of sleep medicine, endocrinology, and oral biology."

Journal • Review • Endocrine Disorders • Gastroenterology • Gastroesophageal Reflux Disease • Obstructive Sleep Apnea • Respiratory Diseases • Sleep Disorder

Efficacy and Safety of Incretin-Based Therapies in Metabolic Dysfunction-Associated Steatotic Liver Disease: A Systematic Review and Meta-Analysis of Randomized Trials (ACG 2026) - "Agents included liraglutide, semaglutide, dulaglutide, tirzepatide, pemvidutide, survodutide, efinopegdutide, and retatrutide... Sixteen MASLD/MASH randomized trials were included. Five biopsy-based trials contributed to MASH/NASH resolution without worsening fibrosis (n=1,226); incretin-based therapy increased resolution versus control (RR 2.80, 95% CI 1.60â4.90; p=0.007; I²=66.6%). Four biopsy-based trials reported fibrosis improvement without MASH worsening (n=1,181), favoring incretin-based therapy (RR 1.52, 95% CI 1.13â2.05; p=0.021; I²=0%)."

Retrospective data • Review • Constipation • Fibrosis • Gastroenterology • Gastrointestinal Disorder • Hepatology • Immunology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease

Plenary I: Retatrutide Once Weekly for the Treatment of Knee Osteoarthritis Pain and Obesity: Results From a 68-Week Phase 3 Randomized Clinical Trial (ACR Convergence 2026) - No abstract available

Clinical • P3 data • Genetic Disorders • Immunology • Musculoskeletal Pain • Obesity • Osteoarthritis • Pain • Rheumatology

Online-Sourced Retatrutide Complicating Impending Diabetic Ketoacidosis in a Patient With Type 1 Diabetes and Concurrent Shigella Gastroenteritis. (PubMed, Cureus) - "This case highlights diagnostic and management challenges created by unregulated research peptides obtained outside healthcare pathways, particularly in patients with type 1 diabetes mellitus where evidence to guide management is limited and clinicians in non-specialist settings may be unfamiliar with these agents. As access expands through online vendors and social media, clinicians should routinely enquire about prescribed and non-prescribed agents when assessing unexplained illness or metabolic decompensation."

Journal • Acute Kidney Injury • Diabetes • Gastroenterology • Gastrointestinal Disorder • Genetic Disorders • Hypoglycemia • Infectious Disease • Metabolic Disorders • Nephrology • Renal Disease • Type 1 Diabetes Mellitus • Type 2 Diabetes Mellitus

S12: TRIUMPH-2, a Phase 3 clinical trial investigating retatrutide for obesity in patients with type 2 diabetes (EASD 2026) - No abstract available

Clinical • P3 data • Diabetes • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

Cardiometabolic and Renal Effects of Retatrutide: A Systematic Review of Clinical and Translational Evidence (AHA 2026) - "Abstract is embargoed at this time."

Clinical • Review • Nephrology • Renal Disease