Lilly says tirzepatide drove 26% weight loss in two trials, with regain after stopping

Eli Lilly reported on July 27, 2023 that tirzepatide helped adults with obesity lose about 26% of their body weight on average in two late-stage trials, and that people who stopped the drug regained much of that weight. The company released topline results from SURMOUNT-3 and SURMOUNT-4 the same day ^[1][2]. Tirzepatide is sold as Mounjaro for type 2 diabetes, and Lilly is seeking U.S. approval to market it for weight loss ^[1].

SURMOUNT-3 tested whether the drug adds anything after diet and exercise have already worked. All participants first completed a 12-week program of a low-calorie diet, exercise and weekly counseling, and lost an average 6.9% of their body weight ^[2]. The 579 people who lost at least 5% were then assigned at random to tirzepatide or a placebo for 72 weeks ^[1][2]. Those on tirzepatide lost an additional 21.1% of body weight, while the placebo group gained 3.3%, figures reported using an efficacy estimand, a type of analysis that estimates results among participants who stayed on treatment ^[2]. From study entry through 84 weeks, the tirzepatide group's total loss was 26.6%, and 94.4% of them lost at least 5% during the treatment period ^[2]. BioPharma Dive described the same comparison with rounded numbers: 21% further loss on tirzepatide versus a 3% gain on placebo ^[1].

SURMOUNT-4 looked at what happens when treatment stops. All 783 enrollees took tirzepatide for 36 weeks and lost an average 21.1% of their body weight. Of those, 670 were then assigned at random either to keep taking the drug or to switch to placebo for another year ^[1][2]. People who stayed on tirzepatide lost 6.7% more; those switched to placebo regained 14.8% of their weight ^[2]. Over the full 88 weeks, continuous treatment produced a mean loss of about 26% ^[2]. BioPharma Dive reported the same split as roughly 7% more loss on the drug and 15% regain off it ^[1].

The results "showed the highest level of weight loss observed in the SURMOUNT program to date," Jeff Emmick, Lilly's senior vice president of product development, said in a statement ^[2]. He said SURMOUNT-4 reinforces "that obesity should be regarded like other chronic diseases where chronic therapy may be needed to maintain treatment benefits" ^[1][2].

Side effects were similar to those seen in earlier SURMOUNT and SURPASS trials and other approved incretin-based obesity drugs, with gastrointestinal problems most common and mostly mild to moderate ^[2]. The reports do not say how many participants stopped treatment because of side effects.

Both sets of results are topline findings released by the company. Full SURMOUNT-3 results are scheduled for presentation at ObesityWeek and SURMOUNT-4 at the annual meeting of the European Association for the Study of Diabetes, both in October ^[2]. Whether they will be published in a peer-reviewed journal has not been disclosed.

Why it matters for patients

The regain in SURMOUNT-4 suggests tirzepatide's effect on weight depends on continuing to take it. The pattern raises practical questions about coverage, cost and supply for people who expect to stay on treatment long term, though the trials did not measure those issues.

SURMOUNT-3 tested one specific path: a structured 12-week lifestyle program first, then medication. Results may not carry over to people who start a drug without that kind of program, and the trial did not compare starting medication first with lifestyle changes alone.

The figures are averages. Not everyone lost weight: 94.4% of the tirzepatide group in SURMOUNT-3 lost at least 5%, which means about 5.6% did not reach that mark ^[2]. How much weight individuals regained after stopping, and whether regain levels off, has not been reported.

Tirzepatide works on two hormone targets, GLP-1 and GIP. The semaglutide drugs Wegovy and Ozempic hit GLP-1 only; Ozempic is often used off-label for weight loss ^[1]. Lilly's obesity trials were not required for an FDA weight-loss approval but could help doctors decide how to use the drug if it is cleared for that use ^[1].

What happens next

Lilly has said it expects a U.S. approval decision on tirzepatide for weight loss later in 2023, and if approved the drug would compete with Novo Nordisk's Wegovy ^[1]. Detailed results from both trials are due at medical meetings in October ^[2]. Long-term data on heart health, and on what happens when people restart the drug after a break, have not been reported.