期刊
SCIENTIFIC REPORTS
卷 11, 期 1, 页码 -出版社
NATURE PORTFOLIO
DOI: 10.1038/s41598-021-94896-w
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资金
- Japan Society for the Promotion of Science [19K08990]
- Kawasaki Medical School [R02-003, R02-026]
- Boehringer Ingelheim
- Grants-in-Aid for Scientific Research [19K08990] Funding Source: KAKEN
The combination therapy of DPP-4 inhibitor and SGLT2 inhibitor has more beneficial effects on beta-cell mass and function, especially in the early phase of diabetes.
Effects of combination therapy of dipeptidyl peptidase-4 (DPP-4) inhibitor and sodium-glucose co-transporter 2 (SGLT2) inhibitor on beta-cells are still unclear, although combination agent of these two drugs has become common in clinical practice. Therefore, we aimed to elucidate the effects of DPP-4 inhibitor and/or SGLT2 inhibitor on beta-cell mass and function and compared their effects between in an early and advanced phase of diabetes. We used 7-week-old db/db mice as an early phase and 16-week-old mice as an advanced phase and treated them for 2 weeks with oral administration of linagliptin, empagliflozin, linagliptin + empagliflozin (L + E group), and 0.5% carboxymethylcellulose (Cont group). Blood glucose levels in Empa and L + E group were significantly lower than Cont group after treatment. In addition, beta-cell mass in L + E group was significantly larger than Cont group only in an early phase, accompanied by increased Ki67-positive beta-cell ratio. In isolated islets, mRNA expression levels of insulin and its transcription factors were all significantly higher only in L + E group in an early phase. Furthermore, mRNA expression levels related to beta-cell differentiation and proliferation were significantly increased only in L + E group in an early phase. In conclusion, combination of DPP-4 inhibitor and SGLT2 inhibitor exerts more beneficial effects on beta-cell mass and function, especially in an early phase of diabetes rather than an advanced phase.
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