Tirzepatide cuts risk for progression to type 2 diabetes for adults with prediabetes
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Key takeaways:
- In SURMOUNT-1, adults with prediabetes receiving tirzepatide were 94% less likely to develop type 2 diabetes than placebo at 176 weeks.
- Those receiving 15 mg tirzepatide lost 22.9% of their body weight.
Adults with prediabetes and overweight or obesity have a 94% lower risk for developing type 2 diabetes with the once-weekly GIP/GLP-1 dual agonist tirzepatide vs. placebo, according to top-line results from the SURMOUNT-1 3-year study.
SURMOUNT-1 was a randomized, double-blind, placebo-controlled trial in which adults with overweight plus one weight-related comorbidity or obesity and without type 2 diabetes were randomly assigned to receive 5 mg, 10 mg or 15 mg tirzepatide (Mounjaro/Zepbound, Eli Lilly) or placebo for 72 weeks. As Healio previously reported, adults with overweight or obesity without diabetes lost 20.9% of their body weight at 72 weeks with 15 mg tirzepatide.
The SURMOUNT-1 trial included 1,032 participants with prediabetes at the start of the study. Those participants continued to receive treatment for 104 weeks beyond the trial’s initial 72-week completion date. Researchers compared progression to type 2 diabetes and change in body weight between adults receiving tirzepatide and those receiving placebo as part of a secondary analysis.
In the efficacy estimand, tirzepatide lowered the risk for progression from prediabetes to type 2 diabetes by 94% compared with placebo (P < .0001). Adults receiving 15 mg tirzepatide lost 22.9% of their body weight by the end of the 176-week treatment period compared with a 2.1% weight reduction for the placebo group (P < .001). Mean weight loss at 176 weeks was 15.4% for adults in the 5 mg tirzepatide group and 19.9% for those receiving 10 mg tirzepatide.
A 17-week off-treatment follow-up period occurred after the 176-week treatment period. While off treatment, some participants who discontinued tirzepatide started to regain weight and had progression to type 2 diabetes. The risk for progression from prediabetes to type 2 diabetes at the end of the off-treatment period was 88% lower in the tirzepatide group compared with placebo (P < .0001).
The safety and tolerability profile of tirzepatide was similar to the primary results of SURMOUNT-1 and other tirzepatide trials. The most common adverse events were gastrointestinal-related and included diarrhea, nausea, constipation and vomiting. Most were mild to moderate in severity.
“Obesity is a chronic disease that puts nearly 900 million adults worldwide at an increased risk of other complications such as type 2 diabetes,” Jeff Emmick, MD, PhD, senior vice president of product development at Lilly, said in the release. “Tirzepatide reduced the risk of developing type 2 diabetes by 94% and resulted in sustained weight loss over the 3-year treatment period. These data reinforce the potential clinical benefits of long-term therapy for people living with obesity and prediabetes.”
Perspective
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We’ve known for decades that lifestyle intervention that produces weight reduction in people living with prediabetes, who typically have overweight or obesity, reduces the risk for new-onset type 2 diabetes. Moreover, pharmaceuticals that modify macronutrient adsorption (acarbose, orlistat), insulin sensitivity (metformin, thiazolidinediones) or insulin secretion (GLP-1 receptor agonists) have also been successful in preventing new-onset type 2 diabetes.
So, what’s new in SURMOUNT-1? This was a trial that included 1,032 participants with prediabetes who were overweight plus had one weight-related comorbidity or obesity without type 2 diabetes, and who were randomly assigned to receive tirzepatide (5, 10 or 15 mg once weekly) or placebo for 72 weeks. No. 1, this is the first such trial with this GIP/GLP-1 dual agonist, and the average weight loss was 20.9%, two to five times higher than in previous type 2 diabetes prevention trials. No. 2, the reduction of new-onset type 2 diabetes was an amazing 94%. Although the initial weight of the participants was not provided, this is an incredible reduction in new-onset type 2 diabetes and far exceeds previous trials. No. 3, the amount of weight reduction seems to be the best predictor of the larger reduction in new-onset type 2 diabetes. However, is this secondary to the weight loss-related improvement in insulin sensitivity alone and/or an increase in glucose-dependent insulin secretion, a pathophysiologic abnormality already known in people with prediabetes?
As a physician scientist, I believe mechanisms are always important to define, however, the substantial reduction in new-onset type 2 diabetes with tirzepatide has immediate impact on a disease process that predicts tremendous medical and socioeconomic benefit. Now, access and affordability remain the major barriers to this outcome.
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