Retatrutide in obesity with type 2 diabetes: 12-14% placebo-adjusted weight loss at 80 weeks

Design

Phase 3, randomised, double-blind, placebo-controlled, 80 weeks

Population

1,152 adults with type 2 diabetes and BMI 27 or more

Primary outcome

Percentage change in body weight at week 80

Effect

-11.8% (95% CI -13.7 to -9.8) at 9 mg and -13.8% (-15.8 to -11.8) at 12 mg vs placebo

TRIUMPH-2 was a phase 3, double-blind, placebo-controlled trial at 92 centres in eight countries. It randomised 1,152 adults with type 2 diabetes and a BMI of 27 or more (mean 38.2), most on oral glucose-lowering drugs, to weekly retatrutide 4, 9 or 12 mg or placebo for 80 weeks. Retatrutide acts on three receptors: GIP, GLP-1 and glucagon.

Weight fell 11.9%, 16.8% and 18.8% on the three doses against 5.1% on placebo, placebo-adjusted differences of 6.9% to 13.8%. Gastrointestinal effects were common: diarrhoea in about a third on the higher doses against 13% on placebo, nausea in up to 28% against 8%. Hypotension (up to 6%) and dysaesthesia, abnormal skin sensation (up to 7%), were more frequent than on placebo. Stopping because of adverse events was 12% on 9 mg and 8% on 12 mg, against 5% on placebo.

Weight loss in people with type 2 diabetes is usually smaller than without it, so these figures are notable. But the trial was funded by the manufacturer, reports weight rather than cardiovascular or kidney outcomes, and the drug was investigational when it was reported. The hypotension and dysaesthesia signals deserve watching in longer use.

• Retatrutide was investigational at the time of this report; it is not a current prescribing option.
• Placebo-adjusted weight loss at 80 weeks was 6.9% (4 mg) to 13.8% (12 mg).
• About 1 in 3 on higher doses had diarrhoea, and 1 in 12 to 1 in 8 stopped for adverse events.
• Hypotension and abnormal skin sensations were more common than on placebo and are worth asking about if the drug becomes available.
• No cardiovascular or kidney outcome data are available yet.

Why it matters

Triple-receptor agonists are pushing weight loss in type 2 diabetes towards what was once only possible with surgery.

Don't overread it

Weight change is not a cardiovascular outcome, and side-effect signals may look different over years rather than 80 weeks.

The statistics, in plain English

All three dose comparisons with placebo have confidence intervals well away from zero, so the weight loss is not chance. Note that placebo participants also lost 5.1%, which is why the placebo-adjusted figure, not the raw one, is the fair measure of the drug's effect.

Read the rest in the app

You have read your two free briefings this month. The app carries all 27 specialties, every morning, free — and this finding is waiting in it.

Get Daily Doctor — free

Scan to keep reading on your phone. No account needed to start.