Improvement of β-Cell Function After Switching From DPP-4 Inhibitors to Oral Semaglutide: SWITCH-SEMA2 Post Hoc Analysis

Hiroshi Nomoto; Sho Furusawa; Hiroki Yokoyama; Yuka Suzuki; Rimi Izumihara; Yuki Oe; Kiyohiko Takahashi; Aika Miya; Hiraku Kameda; Kyu Yong Cho; Jun Takeuchi; Yoshio Kurihara; Akinobu Nakamura; Tatsuya Atsumi

doi:10.1210/clinem/dgae213

Improvement of β-Cell Function After Switching From DPP-4 Inhibitors to Oral Semaglutide: SWITCH-SEMA2 Post Hoc Analysis

J Clin Endocrinol Metab. 2024 May 2:dgae213. doi: 10.1210/clinem/dgae213. Online ahead of print.

Authors

Affiliations

¹ Department of Rheumatology, Endocrinology and Nephrology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo 060-8638, Japan.
² Jiyugaoka Medical Clinic, Obihiro 080-0016, Japan.
³ Division of Diabetes and Endocrinology, Department of Medicine, Hakodate Central General Hospital, Hakodate 040-8585, Japan.
⁴ Sapporo Diabetes and Thyroid Clinic, Sapporo 060-0807, Japan.
⁵ Kurihara Clinic, Sapporo 004-0053, Japan.

PMID: 38695547
DOI: 10.1210/clinem/dgae213

Abstract

Context: Whether continuation of dipeptidyl peptidase-4 inhibitors (DPP-4is) or switching to oral semaglutide is more beneficial for β-cell function is unclear.

Objective: To assess the efficacy of switching from DPP-4is to oral semaglutide for β-cell function compared with DPP-4i continuation.

Methods: Post hoc analysis of SWITCH-SEMA 2, a multicenter prospective randomized controlled trial on the switch to oral semaglutide vs DPP-4i continuation without dose adjustment for 24 weeks in subjects with type 2 diabetes treated with DPP-4is, was conducted. Changes in markers for glucose metabolism, including homeostatic model assessment (HOMA2) scores and disposition index (DI), were compared between the groups.

Results: A total of 146 subjects (semaglutide group, 69; DPP-4i group, 77) were analyzed. In the semaglutide group, glycemic control, liver enzyme deviations, and lipid profiles improved after 24 weeks. Regarding indices for β-cell function, changes in HOMA2-β as well as DI, reflecting the ability of β-cells to compensate for insulin resistance, were significantly higher in the semaglutide group compared with the DPP-4i group (mean change, +10.4 vs +0.6 in HOMA2-β [P = .001] and +0.09 vs 0.0 in DI [P < .001]). Improvement in DI in the semaglutide group was correlated significantly to changes in body mass index (BMI), HbA1c, and fatty liver index reflecting liver steatosis. Multiple linear regression analysis revealed that dose of semaglutide (≥ 7 mg/day), reduction in fatty liver index, and metformin nonuse were independently associated with improvement of DI.

Conclusion: Switching to oral semaglutide ameliorated β-cell function compared with DPP-4is, presumably via tissue-to-tissue crosstalk between liver and β-cells.

Keywords: dipeptidyl peptidase-4 inhibitor; semaglutide; type 2 diabetes; β-cell function.

© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.