tuneTypical Dose
8
Peptide
Retatrutide
Retatrutide
Evidence TierBWADA NOT PROHIBITED
watchEffect Window
Weight and glucose effects detectable by 24 weeks. Stronger separation by 36-48 weeks in phase 2 cohorts.
check_circleCompliance
WADA NOT PROHIBITED
Overview
Clinical Summary
Retatrutide is an investigational incretin-based peptide targeting multiple metabolic receptors. It is studied for obesity and type 2 diabetes outcomes, including large weight loss and glycemic improvements in early trials.
Early clinical trials report substantial weight loss and improvements in glycemic control and lipid biomarkers in obesity and type 2 diabetes. Signals include reductions in liver fat and improvements in cardiometabolic risk markers. Minority interest includes potential benefits for sleep apnea risk factors and broader metabolic disease outcomes, but long-term safety and comparative effectiveness versus approved therapies remain under study.
Triple receptor (GIP, GLP-1, glucagon) agonism with dose-dependent appetite, weight, and metabolic effects in phase 2 settings.
Outcomes
What This Is Expected To Influence
Primary Outcomes
- Percent body-weight reduction at 24 and 48 weeks
- HbA1c change in type 2 diabetes
- Total body fat mass reduction
- Liver fat reduction in MAFLD subgroup
Secondary Outcomes
- Responder rates for ≥5/10/15% weight loss
- Dose escalation tolerability
- GI symptom burden by dose start/pace
Safety
Contraindications and Interactions
Contraindications
- Severe known hypersensitivity to retatrutide
- Uncontrolled severe GI disease or severe uncontrolled emesis risk
- Pregnancy outside approved clinical framework
- Severe pancreatitis history without specialist review
Side effects
- Nausea
- Diarrhea
- Vomiting
- Decreased appetite
Interactions
- Insulin
- Sulfonylureas
- Other medications dependent on narrow hydration/motility windows
Avoid if
- Concurrent unverified compounded peptide use
- Rapid self-escalation
- Concurrent non-prescribed appetite suppressants
Evidence
Study-level References
retatrutide-SRC-001Randomized, double-blind, placebo-controlled phase 2 trial
Sourceopen_in_newJastreboff AM et al. 2023. "Triple-Hormone-Receptor Agonist Retatrutide for Obesity: A Phase 2 Trial." N Engl J Med 389(6): 514-526. [PMID: 37366315](https://pubmed.ncbi.nlm.nih.gov/37366315/)
Population: Adults with obesity or overweight + weight-related condition
Dose protocol: 1 mg, 4 mg, 8 mg, 12 mg weekly with variable start doses over 48 weeks
Key findings: Mean weight change at 24 weeks was approximately -7.2% (1 mg), -12.9% (4 mg), -17.3% (8 mg), -17.5% (12 mg) vs -1.6% placebo. At 48 weeks, reductions were approximately -8.7%, -17.1%, -22.8%, -24.2% for 1/4/8/12 mg cohorts vs -2.1% placebo.
Notes: Supports dose-response and escalation-related GI tolerability patterns.
Paper content
Mean weight change at 24 weeks was approximately -7.2% (1 mg), -12.9% (4 mg), -17.3% (8 mg), -17.5% (12 mg) vs -1.6% placebo. At 48 weeks, reductions were approximately -8.7%, -17.1%, -22.8%, -24.2% for 1/4/8/12 mg cohorts vs -2.1% placebo.
retatrutide-SRC-002Corporate trial result release
Sourceopen_in_newLilly and Company. 2023. "Lilly's phase 2 retatrutide results published in The New England Journal of Medicine show the investigational molecule achieved up to 17.5% mean weight reduction at 24 weeks in adults with obesity and overweight." PRNewswire (Eli Lilly and Company) [Press release](https: //www.prnewswire.com/news-releases/lillys-phase-2-retatrutide-results-published-in-the-new-england-journal-of-medicine-show-the-investigational-molecule-achieved-up-to-17-5-mean-weight-reduction-at-24-weeks-in-adults-with-obesity-and-overweight-301863690.html)
Population: Adults with obesity or overweight enrolled in NCT04881760
Dose protocol: 1 mg, 4 mg, 8 mg, 12 mg once weekly, various starting doses
Key findings: Confirms magnitude, timing and safety framing from trial publication. Notes similar GI profile and escalation-related symptoms.
Notes: Useful for dose-structure context and sponsor-program framing.
Paper content
Confirms magnitude, timing and safety framing from trial publication; notes similar GI profile and escalation-related symptoms.
retatrutide-SRC-003Randomized, double-blind, placebo and active-comparator phase 2 trial
Sourceopen_in_newRosenstock J et al. 2023. "Retatrutide, a GIP, GLP-1 and glucagon receptor agonist, for people with type 2 diabetes." Lancet 402(10401): 529-544. [PMID: 37385280](https://pubmed.ncbi.nlm.nih.gov/37385280/)
Population: Adults with type 2 diabetes
Dose protocol: 0.5 mg, 4 mg, 8 mg, 12 mg weekly (varied starts) for 24/36 weeks
Key findings: HbA1c improvement at 24 weeks and body-weight reductions at 36 weeks in a dose-dependent fashion. No deaths and no severe hypoglycemia in the reported cohort.
Notes: Supports both diabetes-use signal and class-comparable safety framing.
Paper content
HbA1c improvement at 24 weeks and body-weight reductions at 36 weeks in a dose-dependent fashion; no deaths and no severe hypoglycemia in the reported cohort.
retatrutide-SRC-004Randomized, placebo/dulaglutide-controlled substudy
Sourceopen_in_newHeerspink HJ et al. 2025. "Effects of retatrutide on body composition in people with type 2 diabetes: a substudy of a phase 2 trial." Diabetes Obes Metab (Nat Med). [PubMed: 40609566](https://pubmed.ncbi.nlm.nih.gov/40609566/)
Population: Adults with type 2 diabetes from the phase 2 main study
Dose protocol: Retatrutide 0.5 mg, 4 mg, 8 mg, 12 mg weekly, dulaglutide comparator and placebo
Key findings: Total fat mass reduction was greater than placebo and dulaglutide at higher retatrutide doses. Serious adverse events remained low and GI events remained the most frequent.
Notes: Useful for body-composition interpretation and relative harm comparison to dulaglutide.
Paper content
Total fat mass reduction was greater than placebo and dulaglutide at higher retatrutide doses; serious adverse events remained low and GI events remained the most frequent.
retatrutide-SRC-005Randomized, double-blind, placebo-controlled phase 2a trial
Sourceopen_in_newSanyal AJ et al. 2024. "Triple hormone receptor agonist retatrutide for metabolic dysfunction-associated steatotic liver disease: a randomized phase 2a trial." Nat Med. [PMID: 38858523](https://pubmed.ncbi.nlm.nih.gov/38858523/)
Population: Obesity participants with MAFLD and elevated liver fat
Dose protocol: 1 mg, 4 mg, 8 mg, 12 mg weekly for 24-48 weeks
Key findings: Liver fat reductions were substantial and dose-related. Normal liver fat thresholds were reached more often with higher doses.
Notes: Secondary metabolic support claim only. Main stack logic should prioritize glucose/weight endpoints.
Paper content
Liver fat reductions were substantial and dose-related; normal liver fat thresholds were reached more often with higher doses.
retatrutide-SRC-006Systematic review
Sourceopen_in_newHeinkel B et al. 2025. "Efficacy and safety of retatrutide for the treatment of obesity: a systematic review of clinical trials." [PubMed: 40728138](https://pubmed.ncbi.nlm.nih.gov/40728138/)
Population: Adults with obesity from available trials
Dose protocol: Retrospective synthesis of phase 2 obesity doses up to 12 mg
Key findings: Reinforces pooled dose-dependent efficacy trends and highlights limited long-duration safety certainty across all trials.
Notes: Lower evidence priority than primary RCTs. Used for uncertainty context.
Paper content
Reinforces pooled dose-dependent efficacy trends and highlights limited long-duration safety certainty across all trials.
retatrutide-SRC-007Company status and program summary
Sourceopen_in_newLilly. 2025. "What to know about retatrutide." Lilly website FAQ. [What to know](https: //www.lilly.com/news/stories/what-to-know-about-retatrutide)
Population: Broad intended treatment populations
Dose protocol: Ongoing phase 3 programs (obesity and cardio-metabolic indications)
Key findings: Retatrutide is described as investigational, not yet approved and not available for public use.
Notes: Use this source for regulatory status and development phase, not efficacy numerics.
Paper content
Retatrutide is described as investigational; not yet approved and not available for public use.
retatrutide-SRC-008Regulatory safety advisory
Sourceopen_in_newFDA. 2025. "FDA's Concerns with Unapproved GLP-1 Drugs Used for Weight Loss." [FDA](https: //www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/fdas-concerns-unapproved-glp-1-drugs-used-weight-loss)
Population: Public users and healthcare professionals
Dose protocol: Unapproved compounds containing retatrutide sold as peptides for home use
Key findings: FDA warns consumers not to buy unapproved formulations, reinforcing sourcing and authenticity safeguards.
Notes: Complements safety and sourcing section.
Paper content
FDA warns consumers not to buy unapproved formulations, reinforcing sourcing and authenticity safeguards.
retatrutide-SRC-009Bayesian network meta-analysis.
Sourceopen_in_newSinha B, Ghosal S. 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). 2025. doi:10.1002/oby.24360. PMID:40685589.
Population: Adults with overweight or obesity from 19 RCTs.
Dose protocol: Bayesian network meta-analysis of 19 RCTs (29,506 participants) comparing retatrutide, dual agonists, and GLP-1 RAs.
Key findings: Retatrutide achieved the highest odds of 15% or greater weight loss (OR 54.6) with mean loss of 11.0 kg, but carried elevated adverse event risk. Dual agonists achieved equivalent weight loss with better safety.
Notes: Places retatrutide within the comparative incretin landscape. Useful for relative efficacy and safety framing.
Paper content
This Bayesian network meta-analysis pooled 19 RCTs with 29,506 participants to compare retatrutide, dual agonists, and GLP-1 receptor agonists for weight loss. Retatrutide showed the highest odds of achieving 15% or greater weight loss (OR 54.6) with mean weight loss of 11.0 kg, though it also carried elevated adverse event risk. Dual agonists achieved equivalent mean weight loss with a better safety profile. GLP-1 RAs were less effective at 9.0 kg mean loss. Type 2 diabetes reduced efficacy across all classes. This analysis places retatrutide within the broader incretin landscape and highlights its superior efficacy but also the safety tradeoff relative to dual agonists.
retatrutide-SRC-010Phase 2 randomized controlled trial (secondary analysis).
Sourceopen_in_newKanu et al. Appetite, eating attitudes, and eating behaviours during treatment with retatrutide in adults with type 2 diabetes: results of a phase 2 study. Diabetes Obes Metab. 2025. doi:10.1111/dom.70097. PMID:40916752.
Population: Adults with type 2 diabetes.
Dose protocol: Phase 2 secondary analysis, retatrutide 0.5 to 12 mg weekly versus dulaglutide and placebo for 36 weeks in 275 adults with T2D.
Key findings: Higher retatrutide doses (4 mg or above) produced greater reductions in appetite, hunger, and prospective food consumption. Disinhibition decreased and dietary restraint increased at highest dose.
Notes: Clarifies central appetite suppression as a contributing mechanism to weight loss beyond metabolic effects alone.
Paper content
This secondary analysis from the retatrutide phase 2 diabetes trial examined appetite and eating behavior changes in 275 participants over 36 weeks. Higher retatrutide doses (4 mg or above) produced greater reductions in appetite, hunger, and prospective food consumption compared to placebo. Disinhibition decreased and dietary restraint increased at the highest dose. Weight loss correlated with reduced hunger and lower disinhibition. This analysis clarifies that retatrutide's weight-loss mechanism includes central appetite suppression and behavioral eating changes, not just metabolic effects.