Retatrutide side effects and results in studies
In the published retatrutide trials the most common adverse events were gastrointestinal, mainly nausea, diarrhoea and vomiting; they were dose-related, mostly mild to moderate, and less frequent when the trial started at a lower dose. The same trials reported body weight reductions of up to 24.2% at 48 weeks in adults with obesity and HbA1c reductions of up to 1.94% at 40 weeks in type 2 diabetes.
Adverse events reported
| Event | As reported | Source |
|---|---|---|
| Gastrointestinal events (nausea, diarrhoea, vomiting) | The most common adverse events in the phase 2 obesity trial; dose-related, mostly mild to moderate, and partially reduced with a 2 mg rather than 4 mg starting dose | Jastreboff AM et al. |
| Increased heart rate | Dose-dependent increases that peaked at 24 weeks and declined thereafter (phase 2 obesity trial) | Jastreboff AM et al. |
| Increased heart rate, size of effect | A review of the phase 2 obesity trial reported increases of up to 6.7 beats/min and noted this may offset some benefits | PMID 37947489 |
| Any treatment-emergent adverse event | 63% of participants on LY3437943, 60% on dulaglutide and 54% on placebo over 12 weeks; gastrointestinal disorders were the most frequent | Urva S et al. |
| Gastrointestinal events in phase 3 | The most frequent adverse events with retatrutide; generally mild to moderate and subsided over time | Bajaj HS et al. |
| Stopping treatment because of adverse events | 2–5% of participants on retatrutide vs 0% on placebo over 40 weeks | Bajaj HS et al. |
| Severe hypoglycaemia | None reported in the 40-week phase 3 trial | Bajaj HS et al. |
| Deaths | Two deaths, both in the retatrutide 4 mg group, reported as unrelated to the study treatment | Bajaj HS et al. |
| Adverse event risk compared with other agents | A network meta-analysis of 19 trials found retatrutide had the highest adverse event risk of the agents compared | PMID 40685589 |
Outcomes measured
| Outcome | Result as reported | Source |
|---|---|---|
| Body weight, 48 weeks (obesity) | −8.7% (1 mg), −17.1% (4 mg), −22.8% (8 mg), −24.2% (12 mg) vs −2.1% placebo | Jastreboff AM et al. |
| Weight reduction of 15% or more, 48 weeks | 60% (4 mg), 75% (8 mg), 83% (12 mg) vs 2% placebo | Jastreboff AM et al. |
| HbA1c, 40 weeks (type 2 diabetes) | −1.69% (4 mg), −1.86% (9 mg), −1.94% (12 mg) vs −0.81% placebo | Bajaj HS et al. |
| Body weight, 40 weeks (type 2 diabetes) | −11.5% (4 mg), −13.9% (9 mg), −15.3% (12 mg) vs −2.6% placebo | Bajaj HS et al. |
| Liver fat, 24 weeks (MASLD) | −42.9% (1 mg), −57.0% (4 mg), −81.4% (8 mg), −82.4% (12 mg) vs +0.3% placebo | Sanyal AJ et al. |
| Total fat mass by DXA, 36 weeks | −4.9% (0.5 mg), −15.2% (4 mg), −26.1% (8 mg), −23.2% (12 mg) vs −4.5% placebo and −2.6% dulaglutide | Coskun T et al. |
| Appetite and hunger scores, 24 weeks | Greater reductions in overall appetite, hunger and prospective food consumption than placebo at 4 mg and above | Kanu C et al. |
| Blood pressure (meta-analysis) | Systolic −6.79 mmHg and diastolic −2.46 mmHg | PMID 42371360 |
| Blood lipids (meta-analysis) | Total cholesterol −21.88 mg/dL, LDL-C −13.10 mg/dL, triglycerides −40.90 mg/dL; no significant change in HDL-C | PMID 42371360 |
What the studies don't show
These results come from supervised clinical trials of up to 48 weeks, so they do not describe long-term safety, rare adverse events or what happens after treatment stops. The trials used the sponsor's own clinical material with dose escalation schedules, and say nothing about research-grade material. Weight and liver-fat figures are group averages, not predictions for any individual.