Comparative safety and side effects of semaglutide and tirzepatide: Implications for clinical decision-making in obesity management

Nov 2, 2025Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie

Safety and side effects of semaglutide and tirzepatide for managing obesity

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GLP-1 Therapies on OpenScience ↗PubMed ↗DOI ↗

Abstract

Semaglutide and Tirzepatide are associated with gastrointestinal issues and other side effects.

Both drugs are linked to gastrointestinal problems such as nausea, vomiting, and diarrhea.
Instances of pancreatitis have been reported with the use of these incretin-based therapies.
Tirzepatide may offer advantages over standard GLP-1 receptor agonists by promoting bone formation.
Renal protective effects of Tirzepatide include a reduction in albuminuria and a slowing of eGFR decline.
Bone remodeling and disorders related to kidneys and thyroid have been observed with both medications.

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Obesity and diabetes are two faces of the same coin, as both disorders are characterized by insulin action defects. The two gut-derived incretin hormones, glucose-dependent insulinotropic polypeptide (GIP) and Glucagon-like peptide-1 (GLP-1), play a crucial role in glycemic control. Semaglutide is a GLP-1 receptor agonist, while Tirzepatide acts as a dual agonist for the GLP-1 and GIP receptors. Despite its effectiveness in weight loss, various side effects were reported. This review seeks to explore post-marketing concerns regarding the long-term safety and tolerability of these drugs. Both drugs showed gastrointestinal issues, including nausea, vomiting, pancreatitis, and diarrhea. Moreover, bone remodeling, kidney and thyroid disorders were detected. Tirzepatide was preferred over the commonly used single GLP-1 RAs as it has less reported side effects and enhanced benefits in promoting bone formation and its protective renal effects, especially on decreasing albuminuria and eGFR slopes.