Eli Lilly's tirzepatide (Zepbound and Mounjaro) has shown promising results in treating obese and pre-diabetic individuals, according to comprehensive outcomes from the SURMOUNT-1 study. The Phase III trial, spanning 176 weeks, evaluated the efficacy and safety of tirzepatide in adults without type 2 diabetes (T2D) who were either obese or overweight with complications such as cardiovascular disease, dyslipidemia, hypertension, or obstructive sleep apnea (OSA).
The randomized, multi-center, placebo-controlled, double-blind trial included 1,032 pre-diabetic individuals who continued treatment for an additional 104 weeks after the initial 72-week period to assess the impact on body weight and progression to T2D. Tirzepatide, administered weekly via injection, significantly decreased the risk of developing T2D compared to placebo over 176 weeks.
Significant Weight Loss and Diabetes Risk Reduction
At the highest 15mg dose, participants showed a sustained average weight loss of 22.9% during the three-year treatment. A 94% decrease was also observed in the T2D progression risk versus placebo over three years. This translates to a number needed to treat of nine to prevent one case of diabetes.
Mechanism of Action and Additional Benefits
Tirzepatide is a dual glucagon-like peptide-1 (GLP-1) receptor agonist and glucose-dependent insulinotropic polypeptide (GIP). It mimics incretin hormones, which are crucial for the incretin effect following nutrient intake. Further findings from the study indicated improvements in glycemic control, cardiometabolic risk factors, and health-related quality of life associated with the therapy treatment.
Expert Commentary
Eli Lilly product development senior vice-president Jeff Emmick stated, "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. These results underscore the critical role of long-term therapy with effective treatments like tirzepatide to achieve and maintain weight reduction."
Safety Profile
The safety profile of tirzepatide, observed over 193 weeks, remained consistent with previous outcomes. These findings support tirzepatide as a potential long-term treatment option for weight management and diabetes prevention in at-risk individuals. The company reported data from the Phase II SYNERGY-NASH trial of tirzepatide in adult patients with metabolic dysfunction-associated steatohepatitis (MASH) and stage 2 or 3 fibrosis in June 2024.
