Retatrutide side effects: every number from the trials, by dose

Read the last column against the first. On the top dose, nausea was roughly three times as common as on placebo, and vomiting about five times. One in four people on 12 mg vomited at some point during the trial.

Lilly describes these events as mostly mild to moderate and not serious. Two findings suggest they can be managed. In the earlier phase 2 trial, starting at 2 mg rather than 4 mg meant fewer stomach problems at the same final dose. And in a trial in people with type 2 diabetes (TRANSCEND-T2D-1), the stomach effects subsided over time.

On 4 mg, no more people stopped than on placebo. On 12 mg, about one in nine did in the main trial, and 14% to 18% did in the trials that enrolled people with heart disease or knee arthritis. Same dose, different people, different numbers.

Dysesthesia is an unpleasant, abnormal feeling in the skin, usually described as burning or tingling. Lilly's tables group it as a skin burning sensation and related events. It is the one side effect in these trials that the older drugs of this type barely show.

Lilly reports the cases as mostly mild to moderate, and says most resolved while people stayed on the drug. The rate rises with the dose in three of the four trials, which is what a real drug effect looks like.

In the phase 2 trial, heart rate rose with the dose, peaked at 24 weeks and then declined. Zepbound's label shows a smaller version of the same pattern: an average rise of 1 to 3 beats a minute. A faster resting pulse is not a disease, but nobody yet knows what it means over years on this drug.

Blood pressure can also fall. In the trial in people with type 2 diabetes (TRIUMPH-2), low blood pressure was reported by 1% on 4 mg, 5% on 9 mg and 6% on 12 mg, against under 1% on placebo. If you take blood-pressure tablets, raise that with your prescriber before any drug of this type: the tablets often need reducing as the weight comes off.

Serious adverse events count every medical event grave enough to be classed as serious, such as a hospital stay, whether or not the drug caused it. In TRIUMPH-1 they were reported by 10.5% on 12 mg, 7.7% on 9 mg and 7.7% on 4 mg, against 5.5% on placebo.

Six people died during the trial: four on retatrutide (none on 4 mg, three on 9 mg, one on 12 mg) and two on placebo. Three in four participants were on the drug, so the rate was similar in both groups. A trial of this size cannot settle whether a drug changes the risk of dying. That is what the outcomes trial is for.

The step from 4 mg to 9 mg bought about six more percentage points of weight loss. The step from 9 mg to 12 mg bought 1.3 more, and cost four more people in a hundred their place on the drug. On these numbers, most of the weight loss has arrived by 9 mg.