Retatrutide Therapy: What the Clinical Trials Show
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Retatrutide therapy: what the clinical trials actually show
Retatrutide is an investigational triple receptor agonist studied by Eli Lilly for obesity, type 2 diabetes, and fatty-liver related metabolic disease. The early results are promising, but it is important to separate published clinical-trial data from marketing claims.
Not FDA-approved as retatrutide
Physician review required
Mean weight change at 48 weeks
In a phase 2 obesity trial published in The New England Journal of Medicine, the 12 mg retatrutide group had a least-squares mean body-weight change of -24.2% at 48 weeks, compared with -2.1% with placebo.
Adults in the obesity trial
The trial enrolled adults with obesity, or overweight with at least one weight-related condition. It was randomized, double-blind, placebo-controlled, and dose-ranging.
Most common side effects
The most common adverse events reported in the obesity trial were gastrointestinal and dose-related. The study also reported dose-dependent heart-rate increases that peaked around week 24 and declined afterward.
What is retatrutide?
Retatrutide, also known as LY3437943, is designed to activate three hormone-receptor pathways: GIP, GLP-1, and glucagon receptors. This is different from semaglutide, which primarily targets GLP-1, and tirzepatide, which targets GIP and GLP-1.
Because retatrutide is still investigational, the published studies should be viewed as emerging evidence rather than proof of long-term real-world safety or guaranteed results.
Obesity phase 2 trial
The NEJM phase 2 trial found dose-related weight reduction over 48 weeks. At 48 weeks, mean body-weight changes were reported as -8.7% with 1 mg, -17.1% with combined 4 mg groups, -22.8% with combined 8 mg groups, and -24.2% with 12 mg, versus -2.1% with placebo.
At 48 weeks, 83% of participants receiving 12 mg achieved at least 15% weight reduction, compared with 2% receiving placebo.
Type 2 diabetes phase 2 trial
A separate phase 2 study in adults with type 2 diabetes evaluated retatrutide against placebo and dulaglutide. The trial studied HbA1c and body-weight outcomes across multiple doses over 24 to 36 weeks.
This supports why retatrutide is being studied as a metabolic therapy, but it does not mean retatrutide is appropriate for every patient with diabetes or weight concerns.
Fatty liver / MASLD substudy
A randomized phase 2a substudy in participants with metabolic dysfunction-associated steatotic liver disease reported large reductions in liver fat at 24 weeks, especially in the 8 mg and 12 mg groups.
In that substudy, normal liver fat <5% at 24 weeks was reported in 79% of participants receiving 8 mg and 86% receiving 12 mg, compared with 0% receiving placebo.
What this means for MyFlowMD patients
MyFlowMD treats retatrutide as a physician-reviewed metabolic therapy option, not a direct-to-consumer product. Published trial results can help guide the discussion, but medication choice depends on medical history, contraindications, goals, current medications, tolerability, and whether the therapy is clinically appropriate.
Results in clinical trials do not guarantee individual results. Treatment decisions should be made after medical review, with follow-up and dose adjustments when appropriate.
Sources
- Jastreboff AM, et al. Triple-Hormone-Receptor Agonist Retatrutide for Obesity — A Phase 2 Trial. New England Journal of Medicine. 2023;389:514-526. PMID: 37366315.
- Rosenstock J, et al. Retatrutide, a GIP, GLP-1 and glucagon receptor agonist, for people with type 2 diabetes. Lancet. 2023;402:529-544. PMID: 37385280.
- Sanyal AJ, et al. Triple hormone receptor agonist retatrutide for metabolic dysfunction-associated steatotic liver disease: a randomized phase 2a trial. Nature Medicine. 2024;30:2037-2048. PMID: 38858523.
Considering retatrutide?
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