Will Tirzepatide Become a Game-Changer Anti-Obesity Drug?

Tirzepatide is a novel, first-in-class, dual glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist approved by the Food and Drug Administration in 2022 for type 2 diabetes mellitus (T2DM).1 To study the efficacy and safety of tirzepatide for weight reduction in non-diabetic obese individuals, the SURMOUNT-1 trial was conceived, whose findings were re-ported in the recent issue of the New England Journal of Medicine by Jastreboff et al. This was a 72-week phase III, multicenter, double-blind, placebo-controlled, randomized clinical trial in overweight or obese persons, conducted at 119 sites in nine countries, comparing three different doses of tirzepatide with placebo.2 After a 2-week screening period, 2539 participants were randomized in a 1:1:1:1 ratio to receive tirzepatide at a dose of 5 mg, 10 mg, or 15 mg or pla-cebo, administered subcutaneously once weekly for 72 weeks as an adjunct to lifestyle intervention. The lifestyle interven-tion included regular counseling sessions, delivered by a qual-ified healthcare professional or a dietitian, to help the subjects adhere to healthful, balanced meals, with a deficit of 500 calories per day and at least 150 min of physical activity per week. The average weight reduction at 72 weeks was 15% with the 5 mg dose, 19.5% with the 10 mg dose, and 20.9% with the 15 mg dose; while there was only 3.1% weight reduc-tion in the placebo group. Tirzepatide treatment also reduced waist circumference and lowered systolic and diastolic blood pressures, lipids, fasting insulin, and glycated hemoglobin. Serious and non-serious adverse events were limited to gastrointestinal symptoms, such as nausea, diarrhea, and constipation, like those associated with other GLP-1 agonist drugs for weight loss.