Retrospective comparison of the clinical effects of oral semaglutide and SGLT2 inhibitors treatment in patients with type 2 diabetes.

Publisher: Asian Association for the Study of Diabetes and Blackwell Pub. Asia Country of Publication: Japan NLM ID: 101520702 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2040-1124 (Electronic) Linking ISSN: 20401116 NLM ISO Abbreviation: J Diabetes Investig Subsets: MEDLINE

Original Publication: Tokyo : Asian Association for the Study of Diabetes and Blackwell Pub. Asia

Diabetes Mellitus, Type 2*/drug therapy ; Diabetes Mellitus, Type 2*/pathology ; Sodium-Glucose Transporter 2 Inhibitors*/therapeutic use ; Sodium-Glucose Transporter 2 Inhibitors*/administration & dosage ; Glucagon-Like Peptides*/administration & dosage ; Glucagon-Like Peptides*/therapeutic use ; Hypoglycemic Agents*/administration & dosage ; Hypoglycemic Agents*/therapeutic use; Glycated Hemoglobin/analysis ; Blood Glucose/analysis ; Body Weight/drug effects ; Humans ; Retrospective Studies ; Male ; Female ; Middle Aged ; Aged ; Administration, Oral ; Prognosis

Introduction: Recent studies have demonstrated that both oral semaglutide and sodium-glucose cotransporter 2 inhibitors (SGLT2is) have beneficial effects on glycemic and weight management as well as providing renal and cardiovascular protection. However, direct comparisons of the effects of these two drugs in clinical practice remain limited.
Materials and Methods: This study is a single-center, retrospective, observational study. Patients with type 2 diabetes who were initiated on oral semaglutide or SGLT2is and continued treatment for 6 months or more were retrospectively analyzed and compared.
Results: The semaglutide group (84 patients) and the SGLT2is group (231 patients) showed similar, significant reductions in glycated hemoglobin (HbA1c) (semaglutide: -0.88 ± 0.14%; P < 0.01, and SGLT2is: -0.86 ± 0.06%; P < 0.01, at 6 months), body weight (semaglutide: -2.58 ± 0.37 kg; P < 0.01, and SGLT2is: -2.30 ± 0.18 kg; P < 0.01, at 6 months), and fat mass (semaglutide: -2.20 ± 0.50 kg; P < 0.01, and SGLT2is: -1.93 ± 0.44 kg; P < 0.01, at 6 months), being decreased similarly and significantly in both groups. On the other hand, there was a significant reduction in skeletal muscle mass only in the SGLT2is group (semaglutide: -0.10 ± 0.30 kg; P = 0.74, and SGLT2is: -0.40 ± 0.14 kg; P < 0.01 at 6 months).
Conclusions: While both drugs elicited comparable effects on glycemic management and body weight reduction in patients with type 2 diabetes, caution is needed when using SGLT2is in patients at potential risk for sarcopenia, as they may lead to less favorable changes in skeletal muscle mass compared to oral semaglutide.
(© 2026 The Author(s). Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

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Keywords: Oral semaglutide; SGLT2 inhibitors; Skeletal muscle mass

0 (Sodium-Glucose Transporter 2 Inhibitors)
62340-29-8 (Glucagon-Like Peptides)
0 (Glycated Hemoglobin)
0 (Blood Glucose)
0 (Hypoglycemic Agents)
0 (hemoglobin A1c protein, human)

Date Created: 20260120 Date Completed: 20260306 Latest Revision: 20260306

20260307

PMC12950920

10.1111/jdi.70240

41555812