Real-World Comparison of Short-Term Adverse Events, Treatment Persistence, and Efficacy of Semaglutide and Tirzepatide: A Nationwide Multicenter Study

BACKGROUND: Real-world data directly comparing the safety, tolerability, and effectiveness of semaglutide and tirzepatide in patients with obesity remain limited. This nationwide multicenter observational study compared short-term adverse events, treatment discontinuation, body weight loss (BWL), and metabolic outcomes between the two treatments. METHODS: This study included 2,549 patients with obesity treated with semaglutide (n=1,434) or tirzepatide (n=1,115). Adverse events, including time to onset, dose at occurrence, and related discontinuation, were evaluated. Changes in BWL and metabolic parameters up to 6 months were assessed. Subgroup analyses were performed in patients with and without type 2 diabetes mellitus (T2DM). RESULTS: At least one adverse event occurred in 50.9% in the semaglutide group and 51.0% in the tirzepatide group (p=0.524), with gastrointestinal events the most frequently reported. Overall adverse event rates were comparable between groups; however, musculoskeletal and allergic reactions were more common in the tirzepatide group. The onset of gastrointestinal, neuropsychiatric, musculoskeletal symptoms, and hypoglycemia occurred earlier in the tirzepatide group. Discontinuation due to adverse events was similar between groups, except for pancreatic events, which were more frequent in the semaglutide group (p=0.006). Tirzepatide was associated with greater early BWL at all time points. At 6 months, median percentage BWL was 12.6% with semaglutide and 14.4% with tirzepatide. HbA1c reductions were comparable between groups in patients with T2DM. CONCLUSION: In real-world clinical practice, semaglutide and tirzepatide show similar short-term tolerability and treatment persistence, although tirzepatide is associated with a higher incidence of musculoskeletal and allergic reactions and greater early BWL.

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Publication Details

Journal
Obesity Facts
Published
2026-04-24
DOI
https://doi.org/10.1159/000552104
Primary Topic
Diabetes Treatment and Management
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article
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article

Real-World Comparison of Short-Term Adverse Events, Treatment Persistence, and Efficacy of Semaglutide and Tirzepatide: A Nationwide Multicenter Study

Burak Özbaş, Ömercan Topaloğlu, Mustafa Demirpençe, İsmail Yıldız et al.
Obesity Facts
Diabetes Treatment and Management
article

Real-World Comparison of Short-Term Adverse Events, Treatment Persistence, and Efficacy of Semaglutide and Tirzepatide: A Nationwide Multicenter Study

Burak Özbaş, Ömercan Topaloğlu, Mustafa Demirpençe, İsmail Yıldız, Barış Karagün, Çiğdem Tura Bahadır, Kemal Ağbaht, Yagmur Goksoy Solak, Muhammet Kocabaş, Buket Busra Icin, Güven Barış Cansu, Ziynet Alphan Üç, Gamze Akkuş, Volkan Yumuk, Sema Hepşen, Ethem Turgay Cerit, Selin Genç, Çağatay Emir Önder, Mehmet Emin Bozdoğan, Yasin Şimşek, Özge Telci Çaklılı, Pınar Akhanlı, Mustafa Cesur, Berna İmge Aydoğan, Emre Durcan, Adnan Batman, Di̇lek Gogas Yavuz, Süleyman Hilmi İpekçi, Merve Çatak, Mehmet Çağrı Ünal, Cem Haymana, Fettah Acıbucu, Seda Turgut, Işılay Taşkaldıran, İbrahim Demirci, Hakan Doğruel, Hayri Bostan, Gülsüm Karaahmetli, Yusuf Uzun, Şahın Doğanay, Mehmet Güven, Arzu Or Koca, Sakine Güzel Esen, Büşra Özcan, Gülşah Elbüken, Emre Bozkırlı, Seher Tanrıkulu, Özge Özer, Eda Demir Önal, Zuhal Karaca Karagöz, Serpil Salman, Yusuf Kır, Elif Melis Baloğlu Akyol, Osman Onur Daloğlu, Gizem Ertepe Küçükgöde, Mehmet Akif Saltabas, Bora Toros, Sıddika Songül Yalçın, AYŞE KARGILI ÇARLIOĞLU, Sinem Başak Tan, Gizem Ilgın Kaplan, Rıfat Emral, Yahya Erdem İnce, Erman Çakal, Samet Alkan, Yusuf Öztürk, Mehmet Ali Eren, Alper Sönmez, Hüseyin Soylu, Kübra Özsoy, Arif Cengiz Gültekin, Didem Dereli Akdeniz, Sedat Can Güney, Banu Ertürk, Sinem Kıyıcı, Fahri Bayram, Bekir Çakır, Mehmet Aşık, Melia Karaköse, Bülent Can, Tülay Omma
article en

Abstract

BACKGROUND: Real-world data directly comparing the safety, tolerability, and effectiveness of semaglutide and tirzepatide in patients with obesity remain limited. This nationwide multicenter observational study compared short-term adverse events, treatment discontinuation, body weight loss (BWL), and metabolic outcomes between the two treatments. METHODS: This study included 2,549 patients with obesity treated with semaglutide (n=1,434) or tirzepatide (n=1,115). Adverse events, including time to onset, dose at occurrence, and related discontinuation, were evaluated. Changes in BWL and metabolic parameters up to 6 months were assessed. Subgroup analyses were performed in patients with and without type 2 diabetes mellitus (T2DM). RESULTS: At least one adverse event occurred in 50.9% in the semaglutide group and 51.0% in the tirzepatide group (p=0.524), with gastrointestinal events the most frequently reported. Overall adverse event rates were comparable between groups; however, musculoskeletal and allergic reactions were more common in the tirzepatide group. The onset of gastrointestinal, neuropsychiatric, musculoskeletal symptoms, and hypoglycemia occurred earlier in the tirzepatide group. Discontinuation due to adverse events was similar between groups, except for pancreatic events, which were more frequent in the semaglutide group (p=0.006). Tirzepatide was associated with greater early BWL at all time points. At 6 months, median percentage BWL was 12.6% with semaglutide and 14.4% with tirzepatide. HbA1c reductions were comparable between groups in patients with T2DM. CONCLUSION: In real-world clinical practice, semaglutide and tirzepatide show similar short-term tolerability and treatment persistence, although tirzepatide is associated with a higher incidence of musculoskeletal and allergic reactions and greater early BWL.

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