Breaking Down Tirzepatide and SURMOUNT-2 Data, with W. Timothy Garvey, MD

For the second straight year, new data related to the use of tirzepatide (Mounjaro) has headlined the American Diabetes Association (ADA)’s annual meeting. At ADA 2022, SURMOUNT-1 data captivated attendees with the prospect of weight loss at a magnitude comparable to bariatric surgery with a once-weekly injection.

Now, at the 83rd Scientific Sessions of the ADA, data from the SURMOUNT-2 trial paint a more holistic picture of the effects of the dual GIP/GLP-1 receptor agonist as an agent for inducing weight loss in populations with and with type 2 diabetes.

“With a new drug like tirzepatide, it becomes clear we need a weight-centric approach to treating type 2 diabetes when obesity is also present, two conditions that are interwoven for so many Americans,” said principal investigator W. Timothy Garvey, MD, professor of medicine in the Department of Nutrition Sciences at the University of Alabama at Birmingham (UAB) and director of the UAB Diabetes Research Center.² “We are encouraged by these weight loss and glycemic control results, especially as weight loss interventions are typically less effective in patients in diabetes.”

A double-blind, placebo-controlled trial, SURMOUNT-2 enrolled a population of 938 participants who underwent randomization in a 1:1:1 ratio to placebo therapy or tirzepatide 10 or 15 mg. The trial cohort had a mean age of a mean age of 54.2 (SD, 10.6) years, 50.7% were female, and 75.7% were White. At baseline, the cohort had a mean bodyweight of 100.7 kg (SD, 21.1), BMI 36.1 kg/m² (SD, 6.6), and HbA1c 8.02% (SD, 0.89; 64.1 mmol/mol [SD, 9.7]).¹

The trial was designed with a pair of coprimary endpoints, which were the percent change from randomization in body weight and percentage of participants who achieve body weight reduction from randomization of at least 5%.¹

Upon analysis, results suggested the least-squares mean change in body weight at week 72 with tirzepatide 10 mg and 15 mg was -12.8% (SE, 0.6) and -14.7% (SE, 0.5), respectively, compared to -3.2% (SE, 0.5) with placebo therapy, which correlated with an estimated treatment differences relative to placebo of -9.6 percentage points (95% CI, –11.1 to -8.1) with tirzepatide 10 mg and -11.6 percentage points (-13.0 to -10.1) with tirzepatide 15 mg (all P < .0001). Analysis of the second coprimary endpoint suggested 79-83% of patients randomized to tirzepatide achieved a body weight reduction of 5% or greater compared to 32% of those receiving placebo therapy.¹

During the on-site coverage of ADA 2023, our editorial team sat down with Garvey for more insight into the SURMOUNT-2 data, how it complements results of SURMOUNT-1, what his opinion is on some of the other incretin-based therapies presented at ADA 2023, and the importance of implementation science as the community looks to optimize the potential of antiobesity medications.

Relevant disclosures for Dr. Garvey include Boehringer-Ingelheim, Novo Nordisk, Eli Lilly and Company, Merck & Co., Inc., Alnylam Pharmaceuticals, Inc., Fractyl Health, Inc., Inogen, Epitomee, Pfizer Inc., and Neurovalens.

References:

1. Garvey WT, Frias JP, Jastreboff AM, et al. Tirzepatide once weekly for the treatment of obesity in people with type 2 diabetes (SURMOUNT-2): a double-blind, randomised, multicentre, placebo-controlled, phase 3 trial. The Lancet. Published 2023 June 24.
2. Surmount-2 study finds individuals with type 2 diabetes and obesity lost an average of 15% of their body weight when taking tirzepatide. SURMOUNT-2 Study Finds Individuals with Type 2 Diabetes and Obesity Lost an Average of 15% of Their Body Weight when Taking Tirzepatide | ADA. June 23, 2023. Accessed June 25, 2023. https://diabetes.org/newsroom/press-releases/2023/surmount-2-study-finds-individuals-type%202-diabetes-obesity-lost-average-15-percent-body-weight-taking-tirzepatide.