Tirzepatide, CAS No. 2023788-19-2

Tirzepatide is a novel, once-weekly injectable medication that combines glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonism, offering a dual mechanism of action to regulate appetite, energy intake, and metabolic function. This innovative approach has shown significant promise in the management of obesity and related metabolic disorders, including type 2 diabetes and obstructive sleep apnea.

Mechanism of Action

Tirzepatide combines the actions of two incretin hormones, GIP and GLP-1, which play crucial roles in regulating glucose homeostasis and appetite control. GIP enhances insulin secretion in response to nutrient intake, while GLP-1 slows gastric emptying, reduces food intake, and promotes satiety. By targeting both receptors, tirzepatide amplifies the effects on weight management and glycemic control [1].

Clinical Efficacy

Tirzepatide has demonstrated remarkable efficacy in reducing body weight and delaying the progression to type 2 diabetes. In the SURMOUNT-1 trial, participants with obesity and prediabetes treated with tirzepatide achieved substantial weight loss over a 3-year period. At 176 weeks, mean weight loss was 12.3% with the 5-mg dose, 18.7% with the 10-mg dose, and 19.7% with the 15-mg dose, compared to only 1.3% in the placebo group (P<0.001). Additionally, the incidence of type 2 diabetes was significantly lower in the tirzepatide groups (1.3%) compared to the placebo group (13.3%) [1].

In another study involving adults with obesity and type 2 diabetes, tirzepatide provided substantial weight reduction. At week 72, participants treated with tirzepatide 10 mg and 15 mg achieved mean weight loss of 12.8% and 14.7%, respectively, compared to 3.2% with placebo (P<0.0001). Over 79% of participants in the tirzepatide groups achieved a weight reduction of at least 5%, compared to 32% in the placebo group [2].

Safety Profile

The safety profile of tirzepatide is generally well-tolerated, with gastrointestinal adverse events being the most commonly reported. These events, including nausea, diarrhea, and vomiting, are typically mild to moderate in severity and transient, often occurring during the initial dose escalation period [1, 2]. In the SURMOUNT-1 trial, gastrointestinal adverse events were reported in 87.1% of participants treated with tirzepatide, compared to 76.7% in the placebo group [1]. However, these events rarely led to treatment discontinuation, with only a small percentage of participants discontinuing treatment due to gastrointestinal adverse events [1].

References:

1. Tirzepatide for Obesity Treatment and Diabetes Prevention (N Engl J Med 2025;392:958-971, https://doi.org/10.1056/NEJMoa2410819)
2. Tirzepatide once weekly for the treatment of obesity in people with type 2 diabetes (SURMOUNT-2): a double-blind, randomised, multicentre, placebo-controlled, phase 3 trial (The Lancet, Volume 402, Issue 10402, 613 - 626, https://doi.org/10.1016/S0140-6736(23)01200-X)