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

Theodor Bilharz Research Institute

Bibliographic Information

Authors: Fahim S.A.; Attia Y.M.; Messiha A.; Nabawy A.Y.; Refaat F.; El-Maadawy W.H.

Journal: Biomedicine and Pharmacotherapy

Publisher: Elsevier Masson s.r.l.

Publication Date: December 2025

Volume / Issue: Volume 193

Article No.: 118731

ISSN: 7533322

DOI: 10.1016/j.biopha.2025.118731

Scopus: View on Scopus

PubMed: 41177120

Document Type: Review

Access: All Open Access; Gold Open Access

Authors and Affiliations

Fahim S.A., Department of Biochemistry, School of Pharmacy, Newgiza University (NGU), Newgiza, km 22 Cairo-Alexandria Desert Road, Giza, 12577, Egypt; Attia Y.M., Pharmacology Unit, Cancer Biology Department, National Cancer Institute, Cairo University, Kasr Al Eini Street, Fom El Khalig, Cairo, Egypt; Messiha A., Virginia Hospital Center Department of Inpatient Pharmacy, Arlington, VA, United States; Nabawy A.Y., Department of Microbiology, School of Pharmacy, Newgiza University (NGU), Newgiza, km 22 Cairo-Alexandria Desert Road, Giza, 12577, Egypt; Refaat F., School of Pharmacy, New Giza University (NGU), New Giza, km 22 Cairo-Alexandria Desert Road, Giza, 12577, Egypt; El-Maadawy W.H., Pharmacology Department, Theodor Bilharz Research Institute, Warrak El-Hadar, Imbaba (P.O. 30), Giza, 12411, Egypt

Abstract

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. © 2025 The Authors.

Keywords

GIP; Obesity; Semaglutide; Side effects; Tirzepatide; Animals; Anti-Obesity Agents; Clinical Decision-Making; Gastric Inhibitory Polypeptide; Glucagon-Like Peptide 1; Glucagon-Like Peptide-1 Receptor Agonists; Glucagon-Like Peptides; Humans; Hypoglycemic Agents; glucagon like peptide 1; glucagon like peptide 1 receptor agonist; incretin; insulin; antidiabetic agent; antiobesity agent; glucagon like peptide; adverse drug reaction; albuminuria; body weight loss; bone remodeling; clinical decision making; diarrhea; drug therapy; glycemic control; human; obesity management; ossification; pancreatitis; review; side effect; animal; comparative study

Citation Information

Scopus Citations: 7

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