Efficacy and Safety of Tirzepatide on Weight Loss in Patients Without Diabetes Mellitus: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Tirzepatide has positive effects on weight loss in individuals with overweight or obesity. Considering its broad side-effect profile, its efficacy and safety in individuals without diabetes mellitus (DM) are yet to be fully understood. To address this, we conducted a comprehensive meta-analysis of six randomized trials on individuals with overweight or obesity, without DM, which showed that tirzepatide, when compared with placebo, resulted in a change in percentage body weight with a mean difference (MD) of -16.32% (95% CI: -18.35 to -14.29) and change in absolute body weight in kilograms (MD -13.95 kg; -18.83 to -9.07). There were significant reductions in body mass index and waist circumference when compared with placebo, with MDs of -5.89 kg/m2 (-8.97 to -2.81) and -12.31 cm (-13.93 to -10.68), respectively. It was associated with gastrointestinal (GI) side effects: nausea (relative risk [RR] 3.11; 2.74-3.54), vomiting (RR 5.94; 4.50-7.85), diarrhea (RR 2.92; 2.53-3.37), and constipation (RR 2.85; 2.38-3.42). Serious adverse events were not statistically significant (RR 0.93; 0.76-1.13), but serious GI events and discontinuation due to adverse events were significant (RRs 3.07; 2.03-4.66, and 2.29; 1.74-3.01, respectively). In conclusion, this meta-analysis suggests that in patients with overweight or obesity without DM, tirzepatide is effective for significant weight loss. Though the overall risk of serious adverse events is not higher compared with placebo, it carries an elevated risk of GI side effects, serious GI events, and discontinuation due to adverse effects.