Tirzepatide reduces body weight and improves cardiometabolic function in obese patients
1. Tirzepatide treatment significantly reduced body weight and fat composition in obese patients while improving cardiometabolic risk factors and physical function.
2. The frequency of serious adverse events was not significantly different between the tirzepatide and placebo groups.
Level of evidence assessment: 1 (Excellent)
Summary of the study: The global prevalence of obesity is increasing dramatically. This is detrimental to global health, as obesity is associated with several chronic diseases such as cardiovascular disease and type 2 diabetes. Glucagon-like peptide-1 (GLP-1) agonists, which target hormonal pathways stimulated by food, constitute a new class of drugs for the treatment of obesity and diabetes. Glucose-dependent insulinotropic polypeptide (GIP) receptor agonists also regulate energy balance via similar mechanisms. A combination of these two drug classes is believed to produce synergistic effects on weight loss. This phase three randomized controlled trial evaluated the efficacy and safety of various doses of tirzepatide, a dual GLP-1 and GIP receptor agonist, compared to a placebo control group. In addition to the standard lifestyle intervention, participants received once-weekly subcutaneous doses of tirzepatide (5 mg, 10 mg, and 15 mg) or placebo for 72 weeks. The participants were followed for four weeks after the diet. Tirzepatide significantly reduced body weight and fat composition compared to placebo. Tirzepatide treatment was also associated with improvements in cardiometabolic risk factors and physical function. A higher proportion of participants in the treatment group experienced adverse events, the most common of which were gastrointestinal symptoms. However, the prevalence of serious adverse events was statistically similar between the groups. As a limitation, the effect of tirzepatide on overweight patients (body mass index (BMI) 27-30) is not well supported, as overweight participants accounted for only 5.5% of the study. Efficacy and safety data may also have limited generalizability to older patients due to the high proportion of young participants in the study cohort.
Click to read the study in the NEJM
In depth [randomized controlled trial]: In the present study, obese adult patients (n=2539) were randomized in a 1:1:1:1 ratio to tirzepatide (5 mg, 10 mg, or 15 mg) or placebo. Participants received tirzepatide or placebo subcutaneously once weekly along with a standard lifestyle intervention for 72 weeks. Safety data was collected over a four-week follow-up period for participants without prediabetes. A total of 86% of participants completed the trial treatment. At baseline, the majority of participants had a BMI greater than 30 (94.5%) and did not have prediabetes (59.4%). At week 72, weekly doses of 5 mg, 10 mg, and 15 mg tirzepatide resulted in a -15% decline (95% confidence interval). [CI], -15.9 to -14.2), -19.5% (95% CI, -20.4 to -18.5) and -20.9% (95% CI, -21.8 to -19.9) weight reduction, respectively. Placebo resulted in a weight reduction of -3.1% (95% CI, -4.3 to -1.9). All three doses of tirzepatide resulted in significant weight reduction compared to placebo (p
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