What are the side effects and risks of retatrutide?

Gastrointestinal complaints are by far the most commonly reported side effect of retatrutide. Nausea, diarrhoea, vomiting and constipation occur in a substantial proportion of users: in a study of people with type 2 diabetes, 35% of retatrutide users reported these kinds of complaints, compared with 13% in the placebo group. The complaints are predominantly mild to moderate in severity and are strongly dose-dependent. With rapid escalation to 8 mg, 50% of participants experienced gastrointestinal complaints, compared with 13% in the lowest dose group. Starting with a lower dose and increasing it gradually partially reduces these complaints.

Retatrutide also raises heart rate, and this increase is dose-dependent. In studies, heart rate peaked at around 24 weeks and then declined again. What this means for the heart in the long term has not yet been established.

Serious side effects were rare. In the phase 2 study in people with type 2 diabetes, they did not occur more frequently than in the placebo group. No cases of dangerously low blood sugar (severe hypoglycaemia) or deaths were reported. Between 0 and 26% of participants discontinued treatment due to side effects, compared with 0 to 9% in the placebo group. This is therefore more frequent than with placebo, but it still represents a minority.

Little is yet known about the long-term safety of retatrutide. For the broader class of GLP-1-based weight-loss medications, research is ongoing into possible risks of muscle mass loss, reduced bone density, delayed gastric emptying (which is relevant in the context of anaesthesia), disorders of the pancreas and bile ducts, and cancer. Whether and to what extent retatrutide carries these risks must be determined by the ongoing phase 3 study. It also remains unclear how much of the weight loss with retatrutide consists of fat mass versus muscle mass, which is a recognised point of concern for this drug class.