Cardiology Pharmaceuticals

Lilly Shows Tirzepatide Superiority in SURMOUNT-3 and 4

Results from Eli Lilly’s SURMOUNT-3 and SURMOUNT-4 trials are in, and they confirmed that its GLP-1 / GIP agonist tirzepatide (aka Mounjaro) drives significant weight loss among obese or overweight adults who don’t have type 2 diabetes. 

The latest SURMOUNT trials showed that long-term tirzepatide use allows overweight people to shed a massive 26% of their weight. 

  • That’s far more than tirzepatide’s 13.4% to 15.7% reductions among people with T2D in SURMOUNT-2 and significantly more than semaglutide’s (Novo Nordisk Wegovy) 10.9% to 14.9% in previous trials.

The SURMOUNT-3 trial had 806 obese adults without T2D undergo 12 weeks of intensive lifestyle intervention, before randomizing the 579 participants who lost ≥5% of their body weight to receive either tirzepatide or a placebo. After 72 weeks, the tirzepatide group…

  • Lost an additional 21.1% of their weight, while the placebo group regained 3.3%
  • Lost 26.6% of their weight total, including the 12-week lifestyle intervention
  • Had far more users with ≥5% weight loss than the placebo group (94.4% vs. 10.7%)

The SURMOUNT-4 trial had 783 obese adults without T2D take tirzepatide for 36 weeks (not blinded), working their way up to their maximum tolerated dose. Researchers then randomized 670 participants to take either tirzepatide or placebo for another 52 weeks (double blinded). 

  • After the initial 36 weeks, participants lost 21.1% of their body weight
  • After the following 52 weeks, the tirzepatide group lost another 6.7% of their body weight, while the placebo group regained 14.8%
  • Through the 88-week study, the tirzepatide group lost 26% of their body weight

Tirzepatide had a similar safety profile in SURMOUNT-3 and SURMOUNT-4 as its previous trials, most commonly citing mild-moderate gastrointestinal issues. This was also similar to trials for other GLP-1s.

The new trials also strengthen the evidence that GLP-1 weight loss requires continued use, which has been a source of criticism, even though continued use is normal for most other medications for chronic diseases. 

The Takeaway
Twenty-six percent is a massive weight loss number, and suggests that Mounjaro truly might earn its reputation as the “King Kong” of GLP-1s,” assuming its FDA approval process for weight loss goes as Lilly intends.

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