3 year sustained weight loss, powerful prevention of diabetes, and heart failure benefit with tirzepatide (Mounjaro/Zepbound)!

There’s been a flurry of activity in the world of tirzepatide (Mounjaro/Zepbound) in the last week, with the publication of not one, but two landmark papers.

The SURMOUNT-1 3-year data in people with prediabetes was published in the New England Journal of Medicine. This is the longest study with tirzepatide to date. This study included the 1032 people who had prediabetes at the start of the original SURMOUNT-1 trial, and followed them for three years, to see what happened to their weight loss long term, and to see how many people would (or would not) develop type 2 diabetes over this longer term. People in the study were randomized to receive tirzepatide 5mg, 10mg, or 15mg weekly, or placebo. At 176 weeks (over 3 years), weight loss was -12.3% with 5mg, -18.7% with 10mg, and -19.7% with 15mg tirzepatide, vs -1.3% with placebo. These results are very similar to the 1 year results, showing us that weight loss with tirzepatide is sustained. At 176 weeks, people in the tirzepatide groups had a 93% lower risk of developing type 2 diabetes than those in the placebo group. Also, reversion (improvement) from prediabetes to normal sugars was experienced by 89.9%, 91.2%, and 93.3% with 5mg, 10mg, and 15mg tirzepatide respectively, vs 58.9% with placebo. Up to half of the effect to delay onset of type 2 diabetes was due to weight loss. There were no new safety concerns in this 3 year study.

The SUMMIT tirzepatide trial, also published in the New England Journal of Medicine, is the first trial of a GLP-1 based medication to show a reduction in hard endpoints in a HFpEF population. The study randomized 731 people with obesity (BMI of 30 or greater) and heart failure with preserved ejection fraction (HFpEF, ejection fraction at least 50%) to receive tirzepatide (up to 15mg weekly) or placebo for at least 1 year. They found that there was a reduction in the primary composite endpoint of death from cardiovascular causes or a worsening heart failure event of 38% with tirzepatide vs placebo, driven in particular by a reduction in worsening heart failure events requiring hospitalization. The Kansas City Cardiomyopathy Questionaire clinical summary score (KCCQ-CSS – a questionnaire that measures symptoms, physical and social limitations, and quality of life in people with heart failure) was improved by 19.5 points with tirzepatide vs 12.7 with placebo (difference, 6.9 points).

BOTTOM LINE: Tirzepatide is the first GLP1-based medication to show an improvement in hard endpoints in a HFpEF population, yet another leap forward in the ever broadening range of benefits with GLP1-based treatments. We now also have data to show that tirzepatide can support sustained weight loss for at least 3 years, in addition to a very powerful ability to prevent development of type 2 diabetes.

Disclaimer: I am/have been an investigator in clinical trials of tirzepatide. I receive honoraria as a continuing medical education speaker and consultant from the makers of tirzepatide (Eli Lilly).

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