Summary

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• Zepbound (tirzepatide) is indicated as an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management in adults with an initial body mass index (BMI) of 30 kg/m² or greater (obesity). It is also indicated for chronic weight management in adults with an initial BMI of 27 kg/m² or greater (overweight) in the presence of at least one weight-related comorbid condition (e.g., hypertension, dyslipidemia, type 2 diabetes mellitus, obstructive sleep apnea, or cardiovascular disease).
• This summary is based on the review of 20 systematic review(s)/meta-analysis(es). ^[1-20]
• Tirzepatide significantly reduced HbA1c levels, with a mean difference of -2.10% compared to placebo. In dose-specific studies, reductions were -1.96% (15 mg), -1.84% (10 mg), and -1.60% (5 mg). Tirzepatide also showed superior efficacy in reducing HbA1c compared to semaglutide.
• Tirzepatide effectively reduced body weight, with one study reporting a reduction of -8.47 kg. Treatment effects on body weight varied, with reductions of -19.2% for tirzepatide compared to -12.9% for semaglutide. Dose-specific studies reported weight differences of -5.65 kg, -10.06 kg, and -10.63 kg.
• Tirzepatide significantly reduced BMI (MD = -4.02, -3.99, -1.71) and waist circumference (MD = -9.15, -7.71, -4.08). In another study, it reduced waist circumference by -11.4 cm compared to -9.7 cm for semaglutide.
• Tirzepatide demonstrated beneficial effects on lipid profiles, including reductions in triglycerides (TG), very low-density lipoprotein cholesterol (VLDL-C), and total cholesterol (TC).
• Gastrointestinal adverse events: Tirzepatide was associated with a higher incidence of gastrointestinal adverse events, such as nausea, vomiting, diarrhea, and decreased appetite, compared to placebo and basal insulin, but similar to GLP-1 RAs.
• Hypoglycemia: Tirzepatide presented a lower risk of hypoglycemia compared to insulin, but the risk was slightly higher than with placebo and GLP-1 RAs.
• Serious adverse events and specific safety concerns: No significant increase in serious adverse events (e.g., pancreatitis, cholecystitis, MACE-4, hypersensitivity reactions, neoplasms) was observed, although one study noted a significant increase in gallbladder or biliary diseases with tirzepatide compared to placebo or basal insulin.
• The studies included adults with type 2 diabetes and obesity, including specific analyses in Japanese patients and other racial subgroups (Asians vs. non-Asians); non-Asians showed better glycemic control, whereas Asians had more significant body weight reduction and gastrointestinal adverse events. Higher doses of tirzepatide (10 mg and 15 mg) demonstrated stronger efficacy in HbA1c and weight reduction, with improvements in HbA1c maintained up to 40 weeks. No distinct subgroup analyses based on gender or specific age groups were reported.