Tirzepatide Cuts Risk of Progression to T2D by 94% Over 3 Years in Adults with Obesity, Overweight

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Weekly treatment with tirzepatide significantly reduced the risk of progressing from prediabetes to type 2 diabetes (T2D) by 94% among adults with the T2D precursor and obesity or overweight compared to placebo, according to a news release from Eli Lilly.¹

Additional topline findings from the 3-year SURMOUNT-1 study included sustained weight loss through the 176-week treatment period, Lilly stated, with adults who received the highest dose (15 mg) reaching a 22.9% mean decrease in body weight compared to an average 2.1% weight loss among those treated with a placebo.¹

Tirzepatide, a dual GIP (glucose-dependent insulinotropic polypeptide) receptor and GLP-1 (glucagon-like peptide-1) receptor agonist, is approved in the US as Mounjaro for T2D (May 2022) and as Zepbound for chronic weight management (November 2023).

SURMOUNT-1 was a global phase 3 registration trial of tirzepatide and the first to evaluate the medication’s safety and efficacy for weight reduction in adults without T2D.² Study participants had obesity or overweight and at least 1 obesity-related comorbidity. Tirzepatide treatment was an adjunct to a study intervention of caloric reduction and increased physical activity.²

Findings from the trial’s primary analysis after 72 weeks of treatment with tirzepatide or placebo were published in the New England Journal of Medicine in June 2022. Of the study’s original 2539 participants, the 1032 identified at baseline as having prediabetes remained enrolled for another 104 weeks and continued treatment with their original randomly assigned dose of weekly subcutaneous tirzepatide of 5 mg, 10 mg, or 15 mg, or placebo for a total treatment period of 176 weeks.² The treatment period was followed by 17 weeks without treatment, for 193 weeks overall.¹

Researchers reported the average weight loss from study baseline to week 176 as 15.4% (5 mg), 19.9% (10 mg) and 22.9% (15 mg) compared to placebo (2.1%).¹ During the 17-week follow-up period, SURMOUNT-1 participants who had discontinued tirzepatide treatment began to regain lost body weight and showed some increase in progression from prediabetes to T2D, according to Lilly.¹ The result, compared to placebo treatment, was an 88% reduction (P <.001) in risk of worsening hyperglycemia with the potential for developing T2D.¹

Proportion of adults in SURMOUNT-1 phase 3 clinical trial that lost 5% or more and 10% or more of baseline body weight at week 72.²

Additional findings from the original 72-week trial are shown in the figure at right.

In terms of safety and tolerability over the 193-week study, the tirzepatide profile was consistent with the SURMOUNT-1 primary results published at 72 weeks and other clinical studies of the GLP-1/GIP RA for chronic weight management. The most commonly reported adverse events were gastrointestinal in nature, mild to moderate in severity, and most often occurred during the early dose-escalation phase.

The 176-week phase 3 trial in SURMOUNT-1 participants with prediabetes is "the longest completed trial of tirzepatide to date," according to the Lilly statement. The results are consistent with the combined pharmacology of GIP/GLP-1 agonism, the company said.

"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, Lilly senior vice president, product development, said in the statement. "Tirzepatide reduced the risk of developing type 2 diabetes by 94% and resulted in sustained weight loss over the three-year treatment period. These data reinforce the potential clinical benefits of long-term therapy for people living with obesity and pre-diabetes."

When they are available, Lilly plans to submit the study’s detailed results to a peer-reviewed scientific journal. The final readout of the SURMOUNT-1 three-year data will be presented at ObesityWeek 2024, which takes place November 3-6, 2024, in San Antonio, TX.

References
1. Tirzepatide reduced the risk of developing type 2 diabetes by 94% in adults with pre-diabetes and obesity or overweight. Eli Lilly and Company. News release. August 20, 2024. Accessed August 20, 2024. https://investor.lilly.com/news-releases/news-release-details/tirzepatide-reduced-risk-developing-type-2-diabetes-94-adults
2. Halsey G. Tirzepatide treatment leads to weight loss of up to 22.5% in SURMOUNT-1 clinical trial. Patient Care. June 4, 2022. https://www.patientcareonline.com/view/tirzepatide-treatment-leads-to-weight-loss-of-up-to-22-5-in-surmount-1-clinical-trial