Tirzepatide Cut Type 2 Diabetes Risk by 94% in Overweight Adults with Pre-Diabetes

Eli Lilly and Company recently revealed promising outcomes from the 176-week SURMOUNT-1 Phase 3 study, which stands as the longest completed trial of tirzepatide to date. This study focused on adults with pre-diabetes and obesity or overweight, examining the drug’s efficacy and safety for long-term weight management and delaying the progression to type 2 diabetes.

The trial's findings indicate that weekly injections of tirzepatide (available in doses of 5 mg, 10 mg, and 15 mg) significantly reduced the risk of progressing to type 2 diabetes by 94% in pre-diabetic adults who are obese or overweight, compared to a placebo. The highest dose of tirzepatide, 15 mg, resulted in an impressive average weight reduction of 22.9% among participants by the end of the treatment period, contrasting sharply with the 2.1% weight loss observed in the placebo group.

Jeff Emmick, M.D., Ph.D., senior vice president of product development at Lilly, emphasized the significance of these results. He noted that obesity affects nearly 900 million adults worldwide, increasing their risk of conditions like type 2 diabetes. The study underscores the potential of tirzepatide as a long-term therapeutic option for individuals living with obesity and pre-diabetes.

The SURMOUNT-1 study involved 1,032 adults with pre-diabetes and obesity or overweight, with a treatment duration of 176 weeks, followed by a 17-week off-treatment period. The primary analysis, published previously in the New England Journal of Medicine, highlighted substantial weight loss and a decreased risk of diabetes progression with tirzepatide.

In a key secondary endpoint, pooled doses of tirzepatide showed a 94% reduction in the risk of progressing to type 2 diabetes compared to the placebo group by week 176. Additionally, participants experienced significant weight loss, with reductions of 15.4% for the 5 mg dose, 19.9% for the 10 mg dose, and 22.9% for the 15 mg dose, versus 2.1% for the placebo group. These results were consistent even when considering adherence to the treatment regimen.

However, during the 17-week off-treatment period, participants who had discontinued tirzepatide began to regain weight and showed some increase in diabetes progression. Despite this, the risk of progression to type 2 diabetes remained 88% lower compared to the placebo group over the entire study duration.

The safety profile of tirzepatide was consistent with previous findings from the 72-week primary results of the SURMOUNT-1 study and other clinical trials. The most common adverse events were gastrointestinal in nature, including diarrhea, nausea, constipation, and vomiting, and were generally mild to moderate in severity.

Tirzepatide, which activates GIP and GLP-1 receptors, functions by decreasing calorie intake and enhancing insulin sensitivity. These mechanisms contribute to its efficacy in chronic weight management and diabetes risk reduction. The drug was approved by the FDA in 2022 for improving glycemic control in type 2 diabetes and in 2023 for weight management in individuals with obesity or overweight and weight-related comorbid conditions.

The results from the SURMOUNT-1 trial will be detailed in a peer-reviewed journal and presented at ObesityWeek 2024 in November. The study provides robust evidence supporting the use of tirzepatide for both weight loss and diabetes risk reduction in adults with pre-diabetes and obesity or overweight.