retatrutide (LY3437943) / Eli Lilly - LARVOL DELTA

A 5-week treatment with the GLP-1/GIP/glucagon triple receptor agonist retatrutide demonstrates multiple metabolic benefits and strong reduction in liver steatosis in a diet-induced obese MASH mouse model (EASL 2025) - "In the AMLN-diet induced obese MASH mouse model, a 5-week treatment with retatrutide demonstrates multiple metabolic benefits and a strong reduction in liver steatosis. This preclinical data set will help to further assess the efficacy of novel therapies targeting obesity and MASH versus retatrutide as reference."

Preclinical • Fibrosis • Genetic Disorders • Hepatology • Immunology • Inflammation • Metabolic Dysfunction-Associated Steatohepatitis • Obesity

Comparison of anti-obese effects on GLP-1 analogue peptides, Semaglutide, Tirzepatide and Retatrutide using MC4R deficient obesity model mice (ECO 2025) - No abstract available

Preclinical • Genetic Disorders • Obesity • MC4R

TRIUMPH-5: A Study of Retatrutide (LY3437943) Compared to Tirzepatide (LY3298176) in Adults Who Have Obesity (clinicaltrials.gov) - P3 | N=800 | Active, not recruiting | Sponsor: Eli Lilly and Company | Recruiting ➔ Active, not recruiting

Enrollment closed • Genetic Disorders • Obesity

A Study to Measure Calorie Consumption and Usage in Participants With Obesity Using LY3437943 (clinicaltrials.gov) - P1 | N=74 | Active, not recruiting | Sponsor: Eli Lilly and Company | Recruiting ➔ Active, not recruiting

Enrollment closed • Genetic Disorders • Obesity

Effect of Retatrutide Compared With Placebo in Adult Participants With Type 2 Diabetes and Inadequate Glycemic Control With Diet and Exercise Alone (TRANSCEND-T2D-1) (clinicaltrials.gov) - P3 | N=480 | Active, not recruiting | Sponsor: Eli Lilly and Company | Recruiting ➔ Active, not recruiting

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

A Study of LY3437943 in Participants With Impaired and Normal Liver Function (clinicaltrials.gov) - P1 | N=43 | Completed | Sponsor: Eli Lilly and Company | Recruiting ➔ Completed

Trial completion • Hepatitis C • Hepatology • Liver Failure

Effect of Retatrutide Compared With Semaglutide in Adult Participants With Type 2 Diabetes and Inadequate Glycemic Control With Metformin With or Without SGLT2 Inhibitor (TRANSCEND-T2D-2) (clinicaltrials.gov) - P3 | N=1250 | Active, not recruiting | Sponsor: Eli Lilly and Company | Recruiting ➔ Active, not recruiting

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

Comparative Effectiveness of Semaglutide, Liraglutide, Orlistat, and Phentermine for Weight Loss in Obese Individuals: A Systematic Review. (PubMed, Cureus) - "This literature review evaluates and compares the effectiveness of four pharmacological agents semaglutide, liraglutide, orlistat, phentermine, and emerging agents like setmelanotide, amycretin, retatrutide, cagrilintide, and cotadutide in managing weight loss among obese. A detailed analysis was conducted on their mechanisms of action, dosing regimens, efficacy in weight loss, safety profiles, and their impact on obesity-related comorbidities. Although all agents presented distinct benefits, side effects such as gastrointestinal discomfort with orlistat and GLP-1 receptor agonists, and potential dependency with phentermine, necessitate tailored treatment approaches. This review highlights the importance of integrating pharmacotherapy with lifestyle interventions to achieve sustainable weight management and identifies areas for future research to optimize therapeutic outcomes for individuals with obesity."

HEOR • Journal • Review • Cardiovascular • Gastrointestinal Disorder • Genetic Disorders • Obesity

Efficacy of GLP-1 Receptor Agonist-Based Therapies on Cardiovascular Events and Cardiometabolic Parameters in Obese Individuals Without Diabetes: A Meta-Analysis of Randomized Controlled Trials. (PubMed, J Diabetes) - "In nondiabetic individuals with overweight or obesity, GLP-1RA-based therapies significantly reduce cardiovascular events and improve cardiometabolic parameters. These findings underscore the potential for individualized GLP-1RA-based therapies targeting cardiovascular risk factors."

Clinical • Journal • Retrospective data • Review • Cardiovascular • Diabetes • Genetic Disorders • Metabolic Disorders • Myocardial Infarction • Obesity • CRP

SINGLE GLP-1 VS. TRIGONAL GIP, GLP-1, AND GLUCAGON RECEPTOR AGONIST FOR WEIGHT LOSS AND OTHER CARDIOMETABOLIC EFFECTS - Shaharyar Naeem (ACC 2025) - "Retatrutide shows strong potential for weight reduction and cardiometabolic benefits compared to single GLP-1 agonists, such as dulaglutide, in overweight and obese individuals, and it has a favorable safety profile."

Diabetes • Obesity

TRIUMPH-6: A Study of Retatrutide (LY3437943) in the Maintenance of Weight Reduction in Individuals With Obesity (clinicaltrials.gov) - P3 | N=586 | Recruiting | Sponsor: Eli Lilly and Company | Not yet recruiting ➔ Recruiting

Enrollment open • Genetic Disorders • Obesity

Breaking the weight loss paradox: from weight reduction to cardiovascular benefit in obesity treatment. (PubMed, Pol Arch Intern Med) - "More potent agents, such as tirzepatide and retatrutide, have achieved unprecedented weight loss (up to 24%), raising the possibility of greater cardiovascular benefits. As pharmacotherapy continues to evolve, personalized treatment approaches targeting metabolic dysfunction and cardiovascular health will be crucial in redefining obesity care. This review explores the current landscape of obesity pharmacotherapy, its cardiovascular implications, and the emerging role of next-generation therapies in obesity management."

Journal • Review • Atherosclerosis • Cardiovascular • Genetic Disorders • Inflammation • Metabolic Disorders • Obesity

Incretin-based therapies for the treatment of obesity-related diseases (ATTD 2025) - "Liraglutide, semaglutide and tirzepatide are incretin-based therapies currently approved by FDA for the management of obesity, while triple GIPR/GCGR/GLP-1R agonist retatrutide (LY3437943), the cagrilintide/semaglutide (CagriSema) 2.4 mg combination, high-dose oral semaglutide, and oral orforglipron are in advanced stages of development...Liraglutide, semaglutide and tirzepatide are incretin-based therapies currently approved by FDA for the management of obesity, while triple GIPR/GCGR/GLP-1R agonist retatrutide (LY3437943), the cagrilintide/semaglutide (CagriSema) 2.4 mg combination, high-dose oral semaglutide, and oral orforglipron are in advanced stages of development...Moreover, incretin-based therapies have also been proven beneficial on obesity-related comorbidities, such as knee osteoarthritis (KOA), obstructive sleep apnea (OSA) syndrome, and MASLD. Further research is needed to improve our understanding of their effects on obesity-related comorbidities and the..."

Cardiovascular • Congestive Heart Failure • Diabetes • Genetic Disorders • Heart Failure • Hepatology • Immunology • Metabolic Dysfunction-Associated Steatotic Liver Disease • Obesity • Obstructive Sleep Apnea • Osteoarthritis • Pain • Respiratory Diseases • Rheumatology • Sleep Disorder • Type 2 Diabetes Mellitus

Incretin triple agonist retatrutide (LY3437943) alleviates obesity-associated cancer progression. (PubMed, NPJ Metab Health Dis) - "RETA induced immune reprogramming systemically and in the tumor microenvironment with durable anti-tumor immunity evidenced by elevated circulating IL-6, increased antigen presenting cells, reduced immunosuppressive cells, and activation of pro-inflammatory pathways. In sum, our findings suggest that patients with RETA-mediated weight loss may also benefit from reduced cancer risk and improved outcomes."

Journal • Endocrine Cancer • Genetic Disorders • Hepatology • Lung Cancer • Metabolic Disorders • Obesity • Oncology • Pancreatic Cancer • Solid Tumor • IL6

Multifunctional incretin peptides in therapies for type 2 diabetes, obesity and associated co-morbidities. (PubMed, Peptides) - "Recent studies with peptide-based incretin herapies 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)...New incretin-based peptide therapies in development include a long-acting glucagon receptor agonist (LY3324954), dual GLP-1/glucagon receptor agonists (survodutide, pemvidutide, mazdutide, G49), triple GLP-1/GIP/glucagon receptor agonists (retatrutide, efocipegtrutide), a combination of semaglutide with the amylin analogue cagrilintide (CagriSema), a unimolecular GLP-1/amylin receptor dual agonist (amycretin), and a GIP receptor antibody with GLP-1 receptor agonism (MariTide). The creation of multi-targeting incretin-based synthetic peptides provides opportunities for improved management of type 2 diabetes and obesity as well as new therapeutic approaches to an expanding list of associated co-morbidities. The..."

Journal • Cardiovascular • Diabetes • Genetic Disorders • Hepatology • Inflammation • Metabolic Disorders • Nephrology • Obesity • Obstructive Sleep Apnea • Orthopedics • Renal Disease • Respiratory Diseases • Sleep Apnea • Sleep Disorder • Type 2 Diabetes Mellitus

Glucagon-like peptide-1 receptor agonists: a new pharmacological treatment option for psychiatric illnesses? (PubMed, Nervenarzt) - "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...Typical accompanying adverse reactions are gastrointestinal side effects, such as nausea, vomiting, diarrhea, eructation and gastroesophageal reflux. More severe side effects include pancreatitis, allergic reactions, renal function disorders and possibly an increased risk of thyroid cancer."

Journal • Review • Addiction (Opioid and Alcohol) • Allergy • Alzheimer's Disease • Binge Eating Disorder • Cardiovascular • CNS Disorders • Cognitive Disorders • Dementia • Depression • Diabetes • Endocrine Cancer • Gastroenterology • Gastroesophageal Reflux Disease • Gastrointestinal Disorder • Mental Retardation • Metabolic Disorders • Mood Disorders • Oncology • Pancreatitis • Psychiatry • Solid Tumor • Thyroid Gland Carcinoma

The promise of glucagon-like peptide 1 receptor agonists (GLP-1RA) for the treatment of obesity: a look at phase 2 and 3 pipelines. (PubMed, Expert Opin Investig Drugs) - "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 people without diabetes. This review describes results obtained with GLP-1 mono-agonists, GLP-1/GIP dual agonists, GLP-1/glucagon co-agonists, and the triple agonist retatrutide (GIP/GLP-1/glucagon), which have shown beneficial effect both on body weight and steatotic liver disease. A combination of semaglutide (a GLP-1 agonist) and cagrilintide (a long-acting amylin analogue) for weekly administration is currently in phase III development, and so is oral semaglutide and several non-peptide small molecule GLP-1 agonists for oral administration...The GLP-1-based therapies will change the treatment of obesity and its comorbidities including steatotic liver disease in the future...."

Journal • P2 data • Review • Diabetes • Gastrointestinal Disorder • Genetic Disorders • Hepatology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • Obesity

Sex Differences in the Efficacy of Glucagon-Like Peptide-1 Receptor Agonists for Weight Reduction: A Systematic Review and Meta-Analysis. (PubMed, J Diabetes) - "Females lost more weight than males when treated with GLP-1RAs for weight reduction. The sex difference in weight reduction became more pronounced as the degree of weight reduction increased. Indications for obesity could magnify this sex difference."

Clinical • Journal • Retrospective data • Review • Genetic Disorders • Obesity

TRIUMPH-6: A Study of Retatrutide (LY3437943) in the Maintenance of Weight Reduction in Individuals with Obesity (clinicaltrials.gov) - P3 | N=586 | Not yet recruiting | Sponsor: Eli Lilly and Company

New P3 trial • Genetic Disorders • Obesity

Retatrutide melts fat fast but at a cost warn experts (Diabetes.co.uk) - "A new weight loss injection called retatrutide has shown remarkable results in helping users shed weight quickly...Early trials of retatrutide revealed that users could lose up to a quarter of their body weight in under a year, making it nearly twice as effective as Ozempic...Yet, some participants in clinical trials reported losing too much weight too rapidly. One individual dropped 22% of their body weight in just nine months and felt compelled to skip doses to slow down the effects...On social media, some users claim to have accessed retatrutide before official approval in the US or UK...In phase two trials involving 338 obese participants, women on retatrutide lost an average of 28.5% of their body weight over 48 weeks, while men lost an average of 21.2%....More obese participants saw an even greater percentage of weight loss, averaging 26.5% over the same period. Unusually, 100% of trial participants lost at least 5% of their weight."

Retrospective data • Obesity

Comparative efficacy and safety of GLP-1 receptor agonists for weight reduction: A model-based meta-analysis of placebo-controlled trials. (PubMed, Obes Pillars) - "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...The maximum weight reduction effect ranged from 4.25 kg (Liraglutide) to 22.6 kg (Retatrutide). Reported onset times ranged from 6.4 weeks (Orforglipron) to 19.5 weeks (Tirzepatide)...Common adverse events of GLP-1RAs, reported in the literature include nausea, vomiting, diarrhea, and constipation, with a significantly higher incidence of nausea than that of placebo. This study provides a quantitative evaluation of the efficacy and safety of GLP-1RAs and offers valuable insights into the assessment of new drugs for weight reduction."

Clinical • Journal • Retrospective data • Constipation • Gastroenterology • Gastrointestinal Disorder • Genetic Disorders • Obesity • GCG

Comparative efficacy of incretin drugs on glycemic control, body weight, and blood pressure in adults with overweight or obesity and with/without type 2 diabetes: a systematic review and network meta-analysis. (PubMed, Front Endocrinol (Lausanne)) - "Retatrutide (mean difference (MD): -11.91 kg, 95% CI: -19.00 to -4.82, P-score: 0.80, p: 0.0003) and Tirzepatide (MD: -12.78 kg, 95% CI: -16.10 to -9.46, P-score: 0.89, p < 0.0001) exhibited superior efficacy in reducing body weight, with all other agents except Mazdutide (MD: -5.31 kg, 95% CI: -9.78 to -0.84, P-score: 0.37, p: 0.0189) achieving reductions of over 8 kg. Multi-receptor drugs demonstrated substantial therapeutic potential in weight management, glycemic control, and blood pressure regulation in adults with overweight or obesity, with or without diabetes, with a generally favorable safety profile. https://www.crd.york.ac.uk/prospero/, identifier CRD42024554005."

Clinical • Journal • Retrospective data • Review • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

Efficacy and Safety of Glucagon-Like Peptide-1 Receptor Agonists for Weight Loss Among Adults Without Diabetes : A Systematic Review of Randomized Controlled Trials. (PubMed, Ann Intern Med) - "Compared with placebo, tirzepatide (15 mg once weekly) resulted in weight loss of up to 17.8% (95% CI, 16.3% to 19.3%) after 72 weeks of therapy; semaglutide (2.4 mg once weekly), up to 13.9% (CI, 11.0% to 16.7%) after 68 weeks; and liraglutide (3.0 mg once daily), up to 5.8% (CI, 3.6% to 8.0%) after 26 weeks. Retatrutide (12 mg once weekly) produced greater weight loss of up to 22.1% (CI, 19.3% to 24.9%) after 48 weeks; other novel single and combination GLP-1 agents were also efficacious to varying degrees...None. (PROSPERO: CRD42024505558)."

Journal • Review • Constipation • Diabetes • Gastroenterology • Gastrointestinal Disorder • Genetic Disorders • Metabolic Disorders • Obesity

Emerging pharmacotherapies for obesity: A systematic review. (PubMed, Pharmacol Rev) - "Oral semaglutide 50 mg is the only medication that has completed a phase 3 trial. There are 14 ongoing phase 3 trials on glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) (ecnoglutide, orforglipron, and TG103), GLP-1 RA/amylin agonist (CagriSema), GLP-1/glucagon RAs (mazdutide and survodutide), GLP-1/glucose-dependent insulinotropic polypeptide and glucagon RA (retatrutide), dapagliflozin, and the combination sibutramine/topiramate...This systematic review identifies the state and mechanism of action of emerging pharmacotherapies undergoing or having completed phase 2 and phase 3 clinical trials. The information provided herein furthers the understanding of obesity management, implying direct clinical implications and stimulating research initiatives."

Journal • Review • Genetic Disorders • Obesity

Retatrutide: Primary completion of P3 TRIUMPH-3 trial (NCT05882045) for obesity in Jan 2026 (Eli Lilly) - Q4 2024 Results: Completion of P3 TRIUMPH-3 trial for obesity in Feb 2026; Primary completion of P3 TRIUMPH-4 trial (NCT05931367) for obesity in Feb 2026; Completion of P3 TRIUMPH-3 trial for obesity in Mar 2026

Trial completion date • Trial primary completion date • Obesity