The Phase 2 dose-ranging trial of retatrutide (LY3437943) represented an important stage in the clinical development of this investigational triple-receptor agonist. The study examined several retatrutide dose levels in adults with obesity or overweight, helping researchers evaluate changes in body weight, tolerability and safety over a 48-week treatment period.
Retatrutide is designed to activate three metabolic hormone receptors: glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1) and glucagon receptors. For a broader introduction to the molecule, see our guide to what retatrutide is and how its triple-agonist mechanism works.
The multicentre, double-blind, randomised, placebo-controlled Phase 2 study enrolled 338 adults aged 18 to 75 years. Participants had obesity, or overweight together with at least one weight-related health condition. People with diabetes were excluded from the trial.
Participants were assigned to receive placebo or once-weekly subcutaneous retatrutide at maintenance doses of 1 mg, 4 mg, 8 mg or 12 mg. Different starting-dose and dose-escalation schedules were also assessed in some groups. This dose-ranging approach helped researchers explore the relationship between dose, clinical response and tolerability.
Readers interested in the underlying receptor science can also explore our article on the triple-agonist hypothesis and the GLP-1, GIP and glucagon pathways.
The published findings demonstrated a dose-related pattern of body-weight reduction. At 24 weeks, mean weight changes were approximately −7.2% with 1 mg, −12.9% with 4 mg, −17.3% with 8 mg and −17.5% with 12 mg, compared with −1.6% with placebo.
By 48 weeks, mean changes were approximately −8.7%, −17.1%, −22.8% and −24.2% respectively, compared with −2.1% in the placebo group. In the higher-dose groups, the weight-loss curves had not clearly reached a plateau when the 48-week study period ended.
For a more detailed interpretation of these published findings, visit our guide to what the NEJM Phase 2 obesity trial found about retatrutide.
The most commonly reported adverse events were gastrointestinal and were generally described as mild to moderate. These effects occurred more frequently at higher doses. Researchers also observed dose-dependent increases in heart rate, which peaked at around week 24 before subsequently declining.
The Phase 2 results provided important dose-response and safety information that supported progression into larger studies. Retatrutide is now being evaluated through an expanded Phase 3 clinical development programme involving larger participant populations and additional metabolic outcomes.
Retatrutide remains an investigational compound. The findings summarised here describe controlled clinical research and should not be interpreted as evidence of regulatory approval, a therapeutic recommendation or medical advice.
Further Reading: Explore the Retatrutide Knowledge Centre for additional articles covering clinical research, receptor mechanisms and the investigational development of retatrutide.
Educational summary of publicly reported research. Not a therapeutic claim and not medical advice. Retatrutide is investigational and not approved for human use in most jurisdictions.
Expanded investigational programmes are assessing outcomes across larger cohorts. Retatrutide remains investigational and is not approved for human…
Initial investigational studies characterised the pharmacokinetics and tolerability of retatrutide (LY3437943), establishing the groundwork for later dose-ranging research.