REWIND

REWIND stands apart from the other GLP-1 cardiovascular trials because of who it enrolled. Most of those trials recruited people who had already survived a heart attack or stroke — secondary prevention, where events are common and a benefit is easier to detect. REWIND enrolled 9,901 adults with type 2 diabetes of whom the majority had not yet had a cardiovascular event. Gerstein and colleagues published it in The Lancet in 2019.

Participants received dulaglutide (Trulicity) or placebo and were followed for a median of 5.4 years — the longest follow-up in the class at the time. The primary composite of cardiovascular death, nonfatal heart attack and nonfatal stroke occurred in 12.0% on dulaglutide versus 13.4% on placebo, a hazard ratio of 0.88. All-cause mortality did not differ significantly.

Read the absolute numbers alongside the relative ones. A 12% relative reduction sounds substantial; in this population it amounted to 2.4 events per 100 person-years versus 2.7. In a lower-risk group, the same relative effect necessarily produces a smaller absolute payoff, which is exactly why primary-prevention trials need to be so large and so long.

The cost side was real: 47.4% of the dulaglutide group reported a gastrointestinal adverse event during follow-up, against 34.1% on placebo. Over five years, that is a meaningful tolerability burden to weigh against a modest absolute benefit.

The common confusion is treating dulaglutide as a weight-loss drug on the strength of its cardiovascular record. It is not approved for chronic weight management, and its weight effect is smaller than the drugs that are. Worth asking your clinician: whether your cardiovascular risk is high enough for this evidence to change your choice, and whether a GLP-1 with a weight indication makes more sense if weight is your goal. Our REWIND deep dive and dulaglutide alternatives guide compare the options.