What are the side effects and risks of retatrutide?

Gastrointestinal complaints are by far the most commonly reported side effects: nausea, diarrhoea, vomiting and constipation. In the diabetes phase 2 trial, 35% of participants in the retatrutide groups experienced these complaints; a broad review of comparable agents found rates between 47% and 84%. The complaints are usually mild to moderate and are dose-dependent: the higher the dose, the more frequently they occur. Starting at 2 mg instead of 4 mg directly reduces them in part.

Retatrutide also raises heart rate in a dose-dependent manner. That effect peaked after approximately 24 weeks and then diminished again. Whether this has any long-term implications for the heart is not yet clear.

Serious adverse events and deaths were rarely observed in the phase 2 trials. The rate of serious adverse events was comparable to placebo (0-10% active versus 0-12% placebo), and no deaths or cases of serious hypoglycaemia were reported. Nevertheless, up to 26% of participants in active groups discontinued the agent early due to side effects, compared with up to 9% in the placebo groups.

Little is yet known about long-term safety. What happens over time to muscle mass, bone density, the pancreas, the biliary tract and cancer risk is currently being investigated in ongoing phase 3 trials (the so-called TRIUMPH studies). Until those results are available, no one can say with certainty whether retatrutide is safe in the long run.