retatrutide (LY3437943) / Eli Lilly - LARVOL DELTA

Retatrutide: Regulatory submission for obesity in 2026 (Eli Lilly) - Q4 2025 Results

Filing • Obesity

Retatrutide: Data from P3 TRIUMPH-3 trial (NCT05882045) for obesity in 2026 (Eli Lilly) - Q4 2025 Results

P3 data • Obesity

Retatrutide: Data from P3 TRIUMPH-1 trial (NCT05929066) for obesity in 2026 (Eli Lilly) - Q4 2025 Results: Data from P3 TRIUMPH-2 trial (NCT05929079) for obesity in 2026

P3 data • Obesity

Retatrutide: Primary completion and completion of P3 trial (NCT07035093) for obesity in Sep 2027 (Eli Lilly) - Q4 2025 Results

Trial completion date • Trial primary completion date • Obesity

Retatrutide: Primary completion of P3 TRIUMPH-1 trial (NCT05929066) for obesity in Apr 2026 (Eli Lilly) - Q4 2025 Results: Completion of P3 TRIUMPH-1 trial for obesity in May 2026; Primary completion sand completion of P3 TRIUMPH-2 trial (NCT05929079) for obesity in May 2026

Trial completion date • Trial primary completion date • Obesity

Retatrutide: Primary completion of P3 TRIUMPH-3 trial (NCT05882045) for obesity in Apr 2026 (Eli Lilly) - Q4 2025 Results: Completion of P3 TRIUMPH-3 trial for obesity in May 2026; Primary completion and completion of P3 TRIUMPH-Outcomes trial (NCT06383390) for obesity in Feb 2029

Trial completion date • Trial primary completion date • Obesity

Development of the Weight and Emotions Scale (WES). (PubMed, Obes Sci Pract) - P2 | "The WES was developed based on findings from interviews with participants (N = 40) exiting a Phase 2 trial for retatrutide (NCT04881760), a targeted literature review, and interviews with clinicians specialized in obesity medicine (N = 3)...The WES is a new 16-item PRO measure evaluating 13 emotion-related concepts. The WES may be used in clinical trials, observational research, or clinical practice to robustly assess the impact of obesity or overweight and the benefits of treatment on patients' emotional functioning."

Journal • Genetic Disorders • Obesity

Effect of glucagon-like peptide-1 receptor agonists on heart rate in non-diabetic individuals with overweight or obesity: a systematic review and pairwise and network meta-analysis of randomized controlled trials. (PubMed, Eur J Med Res) - "GLP-1RAs were associated with the increasing of HR in patients with overweight or obesity. Orforglipron 36 mg was associated with the most pronounced increase, and tirzepatide 5 mg the least."

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

TRIUMPH-9: A Study of Retatrutide (LY3437943) in Participants Without Type 2 Diabetes Who Have Obesity or Overweight (clinicaltrials.gov) - P3 | N=600 | Recruiting | Sponsor: Eli Lilly and Company | Not yet recruiting ➔ Recruiting

Enrollment open • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

TRIUMPH-9: A Study of Retatrutide (LY3437943) in Participants Without Type 2 Diabetes Who Have Obesity or Overweight (clinicaltrials.gov) - P3 | N=600 | Not yet recruiting | Sponsor: Eli Lilly and Company

New P3 trial • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

TRIUMPH-4: A Study of Retatrutide (LY3437943) Once Weekly in Participants Who Have Obesity or Overweight and Osteoarthritis of the Knee (clinicaltrials.gov) - P3 | N=445 | Completed | Sponsor: Eli Lilly and Company | Active, not recruiting ➔ Completed

Trial completion • Genetic Disorders • Immunology • Obesity • Osteoarthritis • Pain • Rheumatology

A Study to Investigate the Response of Participants With Type 2 Diabetes Mellitus on Once-Weekly Retatrutide to Hypoglycemia (clinicaltrials.gov) - P1 | N=78 | Active, not recruiting | Sponsor: Eli Lilly and Company | Recruiting ➔ Active, not recruiting

Enrollment closed • Diabetes • Hypoglycemia • Metabolic Disorders • Type 2 Diabetes Mellitus

Multi-target incretin-based therapeutics: The rise of dual and triple agonists for metabolic disorders. (PubMed, Eur J Med Chem) - "Dual and triple incretin-based therapies are transforming treatment for type 2 diabetes mellitus, obesity, and non-alcoholic fatty liver disease...Drugs like tirzepatide and retatrutide have shown unprecedented efficacy and tolerability. This review summarizes their mechanisms, clinical progress, and limitations, highlighting how dual and triple incretin agonists may extend or refine the therapeutic benefits established by current GLP-1-based therapies. While challenges remain in safety, accessibility, and long-term use, multi-target agonists represent a promising future in metabolic disease management."

Journal • Review • Addiction (Opioid and Alcohol) • Diabetes • Genetic Disorders • Hepatology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • Obesity • Type 2 Diabetes Mellitus

The Triple-Agonist Revolution: Retatrutide and the Paradigm Shift in Multi-Hormonal Pharmacotherapy for Obesity and Cardiometabolic Comorbidities. (PubMed, Clin Pharmacol Drug Dev) - "Retatrutide exemplifies rational multi-agonist peptide engineering and signals a paradigm shift in systems pharmacology. This perspective underscores the urgent need for scientific engagement, equity considerations, and policy preparedness, positioning retatrutide as a watershed in obesity treatment and a blueprint for future poly-agonist therapies."

Journal • Review • Cardiovascular • Genetic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Obesity

Nephrology : what's new in 2025 (PubMed, Rev Med Suisse) - "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...In patients on hemodialysis, using a dialysate with an intermediate potassium concentration combined with a potassium chelator appears to stabilize serum potassium levels and reduce the occurrence of arrhythmias. Xenotransplantation and ex vivo perfusion techniques are being perfected in the search for a solution to organ shortage."

Journal • Cardiovascular • Chronic Kidney Disease • Diabetes • Immunology • Inflammatory Arthritis • Lupus • Metabolic Disorders • Nephrology • Renal Disease • Transplantation • Type 2 Diabetes Mellitus

Efficacy and Safety of Retatrutide in the Treatment of Diabetes and/or Obesity Comorbid with Chronic Kidney disease: a Systematic Review and Meta-Analysis. (PubMed, Maedica (Bucur)) - "In conclusion, retatrutide exhibits strong efficacy for improving glucose levels and promoting weight loss in patients with diabetes, obesity and CKD, displaying a distinctive dose-response pattern where lower doses may be more effective for glycemic control. Its potential for kidney protection is promising, though clinicians should be mindful of managing gastrointestinal tolerability."

Journal • Retrospective data • Review • Chronic Kidney Disease • Diabetes • Diabetic Nephropathy • Genetic Disorders • Metabolic Disorders • Nephrology • Obesity • Renal Disease • Type 2 Diabetes Mellitus

TRIUMPH-8: A Study of Retatrutide (LY3437943) in Participants With Obesity or Overweight (clinicaltrials.gov) - P3 | N=250 | Recruiting | Sponsor: Eli Lilly and Company | Not yet recruiting ➔ Recruiting

Enrollment open • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

Lilly’s triple agonist, retatrutide, delivered weight loss of up to an average of 71.2 lbs along with substantial relief from osteoarthritis pain in first successful Phase 3 trial (The Malaysian Reserve) - "In TRIUMPH-4, participants with obesity and knee osteoarthritis taking retatrutide 12 mg lost an average of 28.7% of their body weight at 68 weeks; Retatrutide reduced WOMAC pain scores by up to an average of 4.5 points (75.8%) and significantly improved measures of physical function, with more than 1 out of 8 retatrutide-treated patients completely free from knee pain at the end of the trial; Seven additional Phase 3 trials evaluating the investigational once-weekly treatment in obesity and type 2 diabetes are expected to complete in 2026"

P3 data • Trial completion date • Obesity • Type 2 Diabetes Mellitus

IUPHAR Review: From Foe to Friend: Repurposing Glucagon to Treat Obesity and Type 2 Diabetes. (PubMed, Pharmacol Res) - "We focus our review on glucagon receptor (GCGR) agonism, which has recently been combined with both GLP-1R and GLP-1R/GIPR agonism to generate dual (e.g. survodutide, cotatutide, mazdutide, etc) and triple agonists (e.g. retatrutide, etc) for improved body weight loss via energy expenditure stimulation. Mechanistic data has only currently been evaluated in preclinical rodent models and evidence for similar processes in humans is limited. We also provide perspectives about how treatments can improve for future advancement of obesity treatment."

Journal • Review • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

RETRACTED: Retatrutide and Ketoacidosis: Previously Unreported Adverse Effect of the New Triple Agent. (PubMed, Endocr Pract) - "The Editor-in-Chief has lost confidence in the reliability of this abstract. The authors have been informed of the decision to retract and did not agree to the retraction."

Adverse events • Clinical • Journal • Metabolic Disorders

Engineered nutrient-stimulated hormonal multi-agonist for precision targeting of obesity and metabolic disorders. (PubMed, Clin Mol Hepatol) - "Tirzepatide (GLP-1/GIP dual agonist), CagriSema (GLP-1/amylin dual agonist), and retatrutide (GLP-1/GIP/glucagon triple agonist) have achieved unprecedented levels of weight loss and glycemic improvement, with certain agents also demonstrating hepatic, cardiovascular, and inflammatory benefits. Non-peptidyl oral GLP-1RAs, such as orforglipron, offer novel formulation strategies to enhance treatment accessibility and adherence...These therapies are poised to emerge as key components of precision metabolic medicine. This review article explores the mechanistic basis, pharmacological characteristics, and clinical data supporting the use of engineered NUSH-based peptide therapies for obesity and its related metabolic disorders, with particular emphasis on recent progress in the development and clinical application of dual and triple agonists."

Journal • Cardiovascular • Diabetes • Genetic Disorders • Hepatology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • Obesity • Type 2 Diabetes Mellitus

Harnessing GLP-1 Receptor Agonists for Obesity Treatment: Prospects and Obstacles on the Horizon. (PubMed, J Obes) - "Currently, liraglutide, semaglutide, and tirzepatide are FDA-approved for obesity treatment, while other agents are used off-label...Novel agents including CagriSema and higher dose oral semaglutide are advancing through clinical trials, while pivotal trial results for orforglipron, mazdutide, retatrutide, and survodutide are anticipated to further expand the therapeutic landscape...The convergence of pharmacological innovation, digital health strategies, and equitable care initiatives is expected to revolutionize obesity therapeutics in the coming decade. Priorities for future research include sustaining long-term weight loss, establishing disease-modifying potential in nonmetabolic disorders, and addressing health equity concerns to ensure broader global benefit."

Journal • Review • Atherosclerosis • Cardiovascular • Chronic Kidney Disease • CNS Disorders • Congestive Heart Failure • Diabetes • Dyslipidemia • Genetic Disorders • Heart Failure • Hepatology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Nephrology • Obesity • Renal Disease • Type 2 Diabetes Mellitus

Medical Management of Obesity: A Comprehensive Review of Food and Drug Administration (FDA)-Approved and Investigational Therapies. (PubMed, Cureus) - "Approved long-term agents, orlistat, phentermine/topiramate, naltrexone/bupropion, liraglutide, semaglutide, and tirzepatide, differ in mechanism, weight-loss magnitude, and safety considerations. Semaglutide and tirzepatide have redefined expectations for pharmacological weight loss, while next-generation drugs, such as oral glucagon-like peptide 1 receptor agonists (e.g., orforglipron) and multireceptor agonists (e.g., retatrutide), show even greater efficacy in early studies...Future research should prioritize direct comparative trials, real-world effectiveness, long-term safety, and strategies to improve access and adherence. This review offers clinicians a concise, evidence-based guide for obesity pharmacotherapy and outlines key research priorities as the treatment landscape rapidly evolves."

FDA event • Journal • Review • Cardiovascular • Genetic Disorders • Obesity • Oncology • Pancreatic Cancer • Pancreatitis • Thyroid Gland Carcinoma

Diabetes Mellitus and Chronic Kidney Disease: The Future Is Being Surpassed. (PubMed, J Clin Med) - "(5) The mineralocorticoid receptor antagonist (MRA) finerenone has been tested in RCTs as a kidney protective agent...Many novel agents-many of them proven not only for DM management but also for the treatment of obesity with or without DM or heart failure (HF)-are now in development and may be added to the five classical pillars: other non-steroidal MRA (balcinrenone); aldosterone synthase inhibitors (baxdrostat and vicadrostat); other GLP-1 RA (tirzepatide, survodutide, retatrutide, and cagrilintide); ET1 R antagonists, (zibotentan); and soluble guanylate cyclase activators (avenciguat). These new agents aim to slow disease progression further and reduce cardiovascular risk. Future strategies rely on integrated, patient-centered approaches and personalized therapy to curb renal disease and its related complications."

Journal • Review • Cardiovascular • Chronic Kidney Disease • Congestive Heart Failure • Diabetes • Diabetic Nephropathy • Genetic Disorders • Heart Failure • Metabolic Disorders • Nephrology • Obesity • Renal Disease

Retatrutide warning as people risking lives with fake weight-loss drug (Cambridge News) - "Retatrutide - nicknamed the 'Godzilla' or 'Triple-G' jab due to early trial results showing significant weight loss - is still strictly experimental. Yet counterfeit versions are being sold through online and social media shops, Telegram groups and private accounts, often with no medical assessment, no batch control and no legal oversight."

Commercial • Obesity