Tirzepatide and Semaglutide in Type 2 Diabetes Mellitus and Obesity: A Comparative Assessment of Efficacy and Safety (Review)

INTRODUCTION. In the last two decades, pharmacotherapy for obesity and type 2 diabetes mellitus has evolved toward drugs that target the incretin system, such as semaglutide, a glucagon-like peptide-1 (GLP-1) receptoragonist, and tirzepatide, a dual glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 receptor agonist. Both drugs are highly effective in reducing body weight and improving glycemic control, but differences in safetyprofiles necessitate comparative analysis for personalized treatment selection.

Aim

Comparative assessment of the efficacy and safety of tirzepatide and semaglutide in type 2 diabetes mellitus and obesity based on clinical trial data and post-registration pharmacovigilance, identifying key differencesin the spectrum and frequency of adverse drug reactions to develop a strategy for post-registration safety monitoring.

Discussion

In clinical trials, tirzepatide was associated with greater reductions in glycated hemoglobin (in SURPASS-2, the difference ranged from –0.15% to –0.44%) and body weight (in SURMOUNT-2, –14.7% vs. –9.6%in STEP-2) compared with semaglutide; real-world data are consistent with these findings. According to pharmacovigilance databases (VigiBase, FAERS), gastrointestinal disorders are the most frequently reported adversedrug reactions for both agents (up to 70%), with comparable risks of serious gastrointestinal events. Tirzepatide is associated with a higher risk of vomiting, diarrhea, and constipation, whereas specific signals and adverse drugreactions have been identified for semaglutide, including acute kidney injury, nonarteritic anterior ischemic optic neuropathy, depressive disorders, and dysesthesia.

Conclusions

Tirzepatide and semaglutide are effective in reducing glycated hemoglobin levels and body weight (more pronounced for tirzepatide). The safety profiles of the drugs are generally comparable, but differences have been identified in the spectrum of rare adverse drug reactions. Due to the heterogeneity of the design and limited sample sizes, the results of studies on the effects on the thyroid gland, bone tissue, and fertilityrequire confirmation in long-term prospective studies. A comprehensive approach to safety monitoring is needed, combining differentiated risk monitoring for tirzepatide and semaglutide.