Skip to content
Winnowleaf home

Peptide

Retatrutide (GLP-3 Triple Agonist)

Retatrutide (also known as GLP-3 or LY3437943) is an investigational triple hormone receptor agonist (GIP/GLP-1/glucagon) by Eli Lilly for obesity, T2DM, and MASLD. Phase 2: 24.2% weight loss at 48 weeks (NEJM 2023). Phase 3 TRIUMPH-4: 28.7% weight loss at 68 weeks. T2DM Phase 2: HbA1c reduction of 2.2%, 82% achieved HbA1c ≤6.5%. MASLD: 86% liver fat reduction at 48 weeks, 93% achieved <5% liver fat. SAFETY: GI side effects common - nausea (43%), diarrhea (33%), vomiting (21%). Dysesthesia reported in ~20% at higher doses. Seven Phase 3 readouts expected 2026.

Research notice. This page is for education and research. Peptides may not be FDA-approved for human use and may only be legally available for research. Talk to a qualified clinician before considering any peptide.

Best evidence
Grade A
Conditions studied
4
Outcomes
13
Graded outcomes
5413

Evidence by condition

  • Strong
  • Moderate
  • Limited
  • Very limited

4 conditions, plus general outcomes

Type 2 Diabetes

Type 2 Diabetes: outcomes studied for Retatrutide (GLP-3 Triple Agonist)
GradeOutcomeEffectSizeStudiesPeopleStudies list
Glycemic Control (HbA1c)

Phase 2 T2DM (n=281): HbA1c reduction of 2.0-2.2% at 36 weeks. 82% achieved HbA1c ≤6.5%. Superior to 1.5mg dulaglutide comparator. Fasting glucose significantly improved across all doses.

Improves (the measure goes down)Large effect19 studies

Studies that measured glycemic control (hba1c)

and 9 more in the citations list

Obesity

Obesity: outcomes studied for Retatrutide (GLP-3 Triple Agonist)
GradeOutcomeEffectSizeStudiesPeopleStudies list
Gastrointestinal Side Effects

SAFETY CONCERN: Phase 3 TRIUMPH-4: Nausea 38-43%, diarrhea 33-35%, constipation 22-25%, vomiting 20-21%, decreased appetite 18-19%. Generally mild-moderate and manageable with dose titration. Higher dropout rates than placebo.

Worsens (the measure goes up)Moderate effect17 studies

Studies that measured gastrointestinal side effects

and 7 more in the citations list

Body Weight Reduction

Large Decrease

Improves (the measure goes down)Large effect7 studies

Studies that measured body weight reduction

Dysesthesia

SAFETY CONCERN: Unusual side effect - unpleasant skin sensations in ~20% at 12mg dose. Described as mild for most patients, rarely causing discontinuation. Mechanism unclear - may relate to glucagon receptor activation.

Worsens (the measure goes down)Small effect16 studies

Studies that measured dysesthesia

and 6 more in the citations list

Fatty Liver Disease

  • Liver Fat Reduction: improves
Fatty Liver Disease: outcomes studied for Retatrutide (GLP-3 Triple Agonist)
GradeOutcomeEffectSizeStudiesPeopleStudies list
Liver Fat Reduction

Phase 2a MASLD (n=98): 82-86% relative reduction in liver fat at 48 weeks with 8-12mg. 89-93% achieved normal liver fat (<5%). Driven by glucagon receptor activation promoting hepatic lipid oxidation.

Improves (the measure goes down)Large effect16 studies

Studies that measured liver fat reduction

and 6 more in the citations list

Osteoarthritis (OA)

  • Osteoarthritis Pain: improves
Osteoarthritis (OA): outcomes studied for Retatrutide (GLP-3 Triple Agonist)
GradeOutcomeEffectSizeStudiesPeopleStudies list
Osteoarthritis Pain

Phase 3 TRIUMPH-4: WOMAC pain score reduced by 4.5 points (75.8%) at 68 weeks. 12% of patients on 12mg achieved complete pain freedom vs 4.2% placebo. Likely secondary to weight loss reducing joint stress.

Improves (the measure goes down)Large effect15 studies

Studies that measured osteoarthritis pain

and 5 more in the citations list

General

  • Blood Glucose Control: improves
  • Safety/Tolerability: improves
  • Kidney Function: improves
General: outcomes studied for Retatrutide (GLP-3 Triple Agonist)
GradeOutcomeEffectSizeStudiesPeopleStudies list
Blood Glucose Control

19 human trials and systematic reviews support this finding. Evidence includes systematic reviews/meta-analyses. Human clinical trial data available.

Improves (the measure goes down)Moderate effect19 studies

Studies that measured blood glucose control

and 9 more in the citations list

Safety/Tolerability

11 human trials and systematic reviews support this finding. Evidence includes systematic reviews/meta-analyses. Human clinical trial data available.

Improves (the measure goes up)Moderate effect16 studies

Studies that measured safety/tolerability

and 6 more in the citations list

Kidney Function

6 human trials and systematic reviews support this finding. Evidence includes systematic reviews/meta-analyses. Human clinical trial data available.

Improves (the measure goes up)Small effect11 studies

Studies that measured kidney function

and 1 more in the citations list

Liver Protection

6 systematic reviews and preclinical studies support this finding. Evidence includes systematic reviews/meta-analyses. Primarily preclinical evidence.

Improves (the measure goes up)Small effect11 studies

Studies that measured liver protection

and 1 more in the citations list

Anti-Cancer Activity

2 systematic reviews and preclinical studies support this finding. Evidence includes systematic reviews/meta-analyses. Primarily preclinical evidence.

Improves (the measure goes up)Small effect10 studies

Studies that measured anti-cancer activity

Muscle Mass/Function

2 preclinical studies support this finding. Primarily preclinical evidence.

Improves (the measure goes up)Small effect8 studies
GI Protection

2 preclinical studies support this finding. Primarily preclinical evidence.

Improves (the measure goes up)Small effect7 studies

Key findings

  • Glycemic Control (HbA1c)Type 2 DiabetesImproves (the measure goes down)
  • Gastrointestinal Side EffectsObesityWorsens (the measure goes up)
  • Liver Fat ReductionFatty Liver DiseaseImproves (the measure goes down)

Safety notes in the studies

  • SAFETY CONCERN: Unusual side effect - unpleasant skin sensations in ~20% at 12mg dose.

Studies cited

58 studies from PubMed

  1. Retatrutide for the treatment of obesity, obstructive sleep apnea and knee osteoarthritis: Rationale and design of the TRIUMPH registrational clinical trials.Diabetes, obesity & metabolism, 2026 · PMID 41090431
  2. Effects of retatrutide on body composition in people with type 2 diabetes: a substudy of a phase 2, double-blind, parallel-group, placebo-controlled, randomised trialLancet Diabetes Endocrinol, 2025 · PMID 40609566
  3. Efficacy and Safety of Glucagon-Like Peptide-1 Receptor Agonists for Weight Loss Among Adults Without Diabetes : A Systematic Review of Randomized Controlled Trials.Annals of internal medicine, 2025 · PMID 39761578
  4. 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.Frontiers in endocrinology, 2025 · PMID 39968298
  5. What is the pipeline for future medications for obesity?International journal of obesity (2005), 2025 · PMID 38302593
  6. Efficacy of GLP-1-based Therapies on Metabolic Dysfunction-associated Steatotic Liver Disease and Metabolic Dysfunction-associated Steatohepatitis: A Systematic Review and Meta-analysis.The Journal of clinical endocrinology and metabolism, 2025 · PMID 40489581
  7. Antiobesity medications in adult and pediatric obesity and metabolic dysfunction-associated steatotic liver disease.Pharmacological reviews, 2025 · PMID 40554267
  8. Efficacy and safety of anti-obesity drugs in metabolic dysfunction-associated steatotic liver disease: An updated review.World journal of gastroenterology, 2025 · PMID 41025003
  9. Retatrutide improves steatohepatitis in an accelerated mouse model of diet-induced steatohepatitis with a fructose binge.American journal of physiology. Gastrointestinal and liver physiology, 2025 · PMID 41056349
  10. Efficacy and safety of triple hormone receptor agonist retatrutide for the management of obesity: a systematic review and meta-analysis.Expert review of clinical pharmacology, 2025 · PMID 39817343
  11. Comparative efficacy and safety of GLP-1 receptor agonists for weight reduction: A model-based meta-analysis of placebo-controlled trials.Obesity pillars, 2025 · PMID 39980735
  12. Efficacy and safety of retatrutide, a novel GLP-1, GIP, and glucagon receptor agonist for obesity treatment: a systematic review and meta-analysis of randomized controlled trials.Proceedings (Baylor University. Medical Center), 2025 · PMID 40291085
  13. Beyond GLP-1: efficacy and safety of dual and triple incretin agonists in personalized type 2 diabetes care-a systematic review and network meta-analysis.Acta diabetologica, 2025 · PMID 40471293
  14. Efficacy and Safety of GLP-1 Receptor Agonists, Dual Agonists, and Retatrutide for Weight Loss in Adults With Overweight or Obesity: A Bayesian NMA.Obesity (Silver Spring, Md.), 2025 · PMID 40685589
  15. Efficacy and safety of retatrutide for the treatment of obesity: a systematic review of clinical trials.Journal of basic and clinical physiology and pharmacology, 2025 · PMID 40728138
  16. Efficacy and safety of incretin co-agonists: Transformative advances in cardiometabolic healthcare.World journal of cardiology, 2025 · PMID 40949933
  17. Comparison of the effects of Liraglutide, Tirzepatide, and Retatrutide on diabetic kidney disease in db/db mice.Endocrine, 2025 · PMID 39212900
  18. The Effect of Retatrutide on Kidney Parameters in Participants With Type 2 Diabetes Mellitus and/or Obesity.Kidney international reports, 2025 · PMID 40630318
  19. Rationale, Design, and Baseline Characteristics of the TRANSCEND-CKD trial of Retatrutide in Patients with Chronic Kidney Disease.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association, 2025 · PMID 41160422
  20. Diabetes Mellitus and Chronic Kidney Disease: The Future Is Being Surpassed.Journal of clinical medicine, 2025 · PMID 41375628
  21. Efficacy and Safety of Retatrutide in the Treatment of Diabetes and/or Obesity Comorbid with Chronic Kidney disease: a Systematic Review and Meta-Analysis.Maedica, 2025 · PMID 41537067
  22. Saving muscle while losing weight: A vital strategy for sustainable results while on glucagon-like peptide-1 related drugs.World journal of diabetes, 2025 · PMID 40980310
  23. Incretin triple agonist retatrutide (LY3437943) alleviates obesity-associated cancer progression.npj metabolic health and disease, 2025 · PMID 40094000
  24. Evaluating the Rates of Pancreatitis and Pancreatic Cancer Among GLP-1 Receptor Agonists: A Systematic Review and Meta-Analysis of Randomised Controlled Trials.Endocrinology, diabetes & metabolism, 2025 · PMID 40988099
  25. Quantitative Comparison of Glucagon-Like Peptide-1 Receptor Agonists on Weight Loss in Adults: A Systematic Review and Model-Based Meta-Analysis.Diabetes technology & therapeutics, 2025 · PMID 39911047
  26. Emerging pharmacotherapies for obesity: A systematic review.Pharmacological reviews, 2025 · PMID 39952695
  27. The promise of glucagon-like peptide 1 receptor agonists (GLP-1RA) for the treatment of obesity: a look at phase 2 and 3 pipelines.Expert opinion on investigational drugs, 2025 · PMID 40022548
  28. Sex Differences in the Efficacy of Glucagon-Like Peptide-1 Receptor Agonists for Weight Reduction: A Systematic Review and Meta-Analysis.Journal of diabetes, 2025 · PMID 40040445
  29. Comparative Effectiveness of Semaglutide, Liraglutide, Orlistat, and Phentermine for Weight Loss in Obese Individuals: A Systematic Review.Cureus, 2025 · PMID 40206909
  30. 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.Journal of diabetes, 2025 · PMID 40207414
  31. Appetite, eating attitudes, and eating behaviours during treatment with retatrutide in adults with type 2 diabetes: Results of a phase 2 study.Diabetes, obesity & metabolism, 2025 · PMID 40916752
  32. Perceived benefits of treatment for obesity with retatrutide: A qualitative study of patients in a phase 2 clinical trial.Obesity pillars, 2025 · PMID 41216380
  33. Medical Management of Obesity: A Comprehensive Review of Food and Drug Administration (FDA)-Approved and Investigational Therapies.Cureus, 2025 · PMID 41393574
  34. Triple hormone receptor agonist retatrutide for metabolic dysfunction-associated steatotic liver disease: a randomized phase 2a trialNat Med, 2024 · PMID 38858523
  35. A review of an investigational drug retatrutide, a novel triple agonist agent for the treatment of obesityObes Rev, 2024 · PMID 38367045
  36. Recent advances in the treatment of type 2 diabetes mellitus using new drug therapies.The Kaohsiung journal of medical sciences, 2024 · PMID 38183334
  37. Future is Brighter: New Potential Paradigm-Shifting Medications and Regimens for Diabetes and Obesity.Current diabetes reviews, 2024 · PMID 38275036
  38. Oral glucagon-like peptide-1 receptor agonists and combinations of entero-pancreatic hormones as treatments for adults with type 2 diabetes: where are we now?Expert opinion on pharmacotherapy, 2024 · PMID 38753454
  39. Efficacy and Safety of GLP-1 Medicines for Type 2 Diabetes and Obesity.Diabetes care, 2024 · PMID 38843460
  40. Comparative Meta-Analysis of Retatrutide Versus Placebo and Dulaglutide for Weight Loss and Diabetes Management: Insights From Clinical Trials.American journal of therapeutics, 2024 · PMID 38976545
  41. The power of three: Retatrutide's role in modern obesity and diabetes therapy.European journal of pharmacology, 2024 · PMID 39515565
  42. At ObesityWeek, More Data and Questions About Semaglutide, Tirzepatide, and Retatrutide.JAMA, 2024 · PMID 38055301
  43. Gut hormones and appetite regulation.Current opinion in endocrinology, diabetes, and obesity, 2024 · PMID 38511400
  44. Advancements in pharmacological treatment of NAFLD/MASLD: a focus on metabolic and liver-targeted interventions.Gastroenterology report, 2024 · PMID 38681750
  45. The impact of weight loss on fat-free mass, muscle, bone and hematopoiesis health: Implications for emerging pharmacotherapies aiming at fat reduction and lean mass preservation.Metabolism: clinical and experimental, 2024 · PMID 39481534
  46. Sex, race, and BMI in clinical trials of medications for obesity over the past three decades: a systematic review.The lancet. Diabetes & endocrinology, 2024 · PMID 38723646
  47. Seven glucagon-like peptide-1 receptor agonists and polyagonists for weight loss in patients with obesity or overweight: an updated systematic review and network meta-analysis of randomized controlled trials.Metabolism: clinical and experimental, 2024 · PMID 39305981
  48. Effects of once-weekly subcutaneous retatrutide on weight and metabolic markers: A systematic review and meta-analysis of randomized controlled trials.Metabolism open, 2024 · PMID 39318607
  49. Approved and Emerging Hormone-Based Anti-Obesity Medications: A Review Article.Indian journal of endocrinology and metabolism, 2024 · PMID 39676791
  50. Triple-Hormone-Receptor Agonist Retatrutide for Obesity - A Phase 2 TrialN Engl J Med, 2023 · PMID 37366315
  51. Retatrutide, a GIP, GLP-1 and glucagon receptor agonist, for people with type 2 diabetes: a randomised, double-blind, placebo and active-controlled, parallel-group, phase 2 trial conducted in the USALancet, 2023 · PMID 37385280
  52. Is retatrutide (LY3437943), a GLP-1, GIP, and glucagon receptor agonist a step forward in the treatment of diabetes and obesity?Expert opinion on investigational drugs, 2023 · PMID 37086147
  53. Retatrutide showing promise in obesity (and type 2 diabetes).Expert opinion on investigational drugs, 2023 · PMID 37947489
  54. Triple-Hormone Combination Retatrutide Induces 24% Body Weight Loss.JAMA, 2023 · PMID 37405802
  55. Triple-Hormone-Receptor Agonist Retatrutide for Obesity.The New England journal of medicine, 2023 · PMID 37888925
  56. Triple-Hormone-Receptor Agonist Retatrutide for Obesity.The New England journal of medicine, 2023 · PMID 37888926
  57. Triple-Hormone-Receptor Agonist Retatrutide for Obesity. Reply.The New England journal of medicine, 2023 · PMID 37888927
  58. Retatrutide: a triple incretin receptor agonist for obesity management.Expert opinion on investigational drugs, 2023 · PMID 37902090