Data from the Phase III SURMOUNT-1 study indicates that Eli Lilly's tirzepatide (Zepbound and Mounjaro) provides sustained and clinically meaningful benefits for adults with pre-diabetes and obesity or overweight over a 176-week treatment period. The study, published in The New England Journal of Medicine and presented at ObesityWeek 2024, revealed that weekly injections of tirzepatide at 5 mg, 10 mg, and 15 mg doses significantly lowered the risk of progressing to type 2 diabetes.
Significant Weight Loss and Diabetes Prevention
The SURMOUNT-1 trial, a multi-center, randomized, double-blind, parallel, placebo-controlled study, compared the efficacy and safety of tirzepatide (5 mg, 10 mg, and 15 mg) to placebo. The trial included adults without type 2 diabetes who had obesity or overweight, along with at least one comorbidity such as hypertension, dyslipidemia, obstructive sleep apnea, or cardiovascular disease. Following the initial 72-week completion date, 1,032 patients with pre-diabetes continued in the trial for an additional 104 weeks to assess the impact on body weight and the potential differences in progression to type 2 diabetes after three years of tirzepatide treatment compared to placebo.
According to Ania Jastreboff, MD, PhD, director of the Yale Obesity Research Center, individuals treated with tirzepatide experienced an average weight loss of up to 23% and maintained this reduction for over three years, while also benefiting from a substantial decrease in the risk of developing type 2 diabetes. "In absolute terms, nearly 99% of individuals treated with tirzepatide remained diabetes-free at 176 weeks," Jastreboff noted.
Study Results: Weight Loss and Risk Reduction
The study results showed that tirzepatide achieved an average weight loss of 22.9% at the 15 mg dose, with 99% of participants remaining diabetes-free compared to the placebo group. The 5 mg and 10 mg doses resulted in average weight losses of 15.4% and 19.9%, respectively. Furthermore, tirzepatide reduced the risk of developing type 2 diabetes by 94% and demonstrated positive effects on glycemic control, cardiometabolic health factors, and quality of life.
Safety and Tolerability
Common adverse events reported in the study included COVID-19, nausea, diarrhea, and constipation, with most symptoms being mild to moderate in severity. The overall safety and tolerability profile of tirzepatide at 193 weeks was consistent with previously published results at 72 weeks for SURMOUNT-1 and other tirzepatide clinical studies focused on weight reduction and long-term maintenance.
Implications for Diabetes Treatment
Jeff Emmick, MD, PhD, SVP, product development, Lilly, emphasized the significance of these findings: "In the SURMOUNT-1 three-year study of tirzepatide, an average weight reduction of up to 22.9% was accompanied by a hazard ratio of 0.06 for progression to type 2 diabetes. This translates to a risk reduction of 94% and a number needed to treat of nine to prevent one case of diabetes." He further highlighted the critical role of long-term therapy with effective treatments like tirzepatide in achieving and maintaining weight reduction.
According to the Centers for Disease Control and Prevention, 11.6% of the US population has some form of diabetes, including 38.1 million adults over 18 years of age. The prevalence increases with age, with 29.9% of the population over 65 years having diabetes. Additionally, 8.7 million adults over 18 who meet laboratory criteria for diabetes are unaware of or do not report having the condition.
