A randomized, placebo-controlled trial to assess the efficacy and safety of sitagliptin in Japanese patients with type 2 diabetes and inadequate glycaemic control on ipragliflozin

Abstract

Aims: To investigate the efficacy, safety and tolerability of sitagliptin 50 mg once daily added to ipragliflozin 50 mg once daily monotherapy in Japanese patients with type 2 diabetes (T2D).

Materials and methods: Japanese patients with T2D and glycated haemoglobin (HbA1c) 7.0% to 10.0% while treated with ipragliflozin 50 mg once daily were randomized 1:1 to additional treatment with sitagliptin 50 mg once daily (N = 70) or matching placebo (N = 71) for 24 weeks. The primary efficacy endpoint was change in HbA1c at Week 24. Secondary efficacy endpoints were changes in 2-hour post-meal glucose (PMG), total PMG 0- to 2-hour area under the curve (AUC0-2h ), and fasting plasma glucose (FPG).

Results: Baseline characteristics were similar in the two groups (mean age 55.5 years, mean baseline HbA1c 8.0%). After 24 weeks, the addition of sitagliptin provided significantly greater reduction in HbA1c compared to placebo (least squares [LS] mean difference -0.83% [95% confidence interval -1.05, -0.62]; P <0.001). Significant reductions were also observed in all secondary endpoints: LS mean differences from placebo in changes in 2-hour PMG, total PMG AUC0-2h , and FPG were -42.5 mg/dL, -67.0 mg·h/dL and -11.2 mg/dL, respectively (all P <0.001). The incidence of adverse events (AEs) overall and incidence of predefined AEs of clinical interest (symptomatic hypoglycaemia, urinary tract infection, genital infection, hypovolaemia and polyuria/pollakiuria) were similar in the two groups.

Conclusions: In Japanese patients with T2D, sitagliptin 50 mg once daily added to ipragliflozin 50 mg once daily monotherapy provided significant improvement in glycaemic control and was generally well tolerated. ClinicalTrials.gov: NCT02577016.

Keywords: DPP-4 inhibitor; SGLT2 inhibitor; combination therapy; incretins.

Conflict of interest statement

YS has received contracted/collaborative research funds from Bayer, Boehringer Ingelheim and Terumo, scholarship grants from Arklay, Novo Nordisk, Ono, Sumitomo Dainippon and Taisho Toyama, and fees for consulting and/or lectures from Becton Dickinson, Boehringer Ingelheim, Kao, MSD, Novo Nordisk, Taisho, Taisho Toyama and Takeda. KK has received scholarship grants from Boehringer Ingelheim, Daiichi Sankyo and Mitsubishi Tanabe, and fees for consulting and/or lectures from Astellas, AstraZeneca, Boehringer Ingelheim, Fujifilm, Kissei, Kowa, Mitsubishi Tanabe, MSD, Novartis, Novo Nordisk, Sanofi, Sanwa Kagaku, Sumitomo Dainippon, Taisho Toyama and Takeda. TK has received contract research funds from AstraZeneca and Takeda, joint research funds from Daiichi Sankyo, grants from Astellas, Daiichi Sankyo, Eli Lilly, Kissei, Mitsubishi Tanabe, MSD, Novo Nordisk, Ono, Sanofi, Sumitomo Dainippon, Taisho and Takeda, fees for consulting and/or lectures from Abbott, Astellas, AstraZeneca, Bayer, Boehringer Ingelheim, Cosmic, Daiichi Sankyo, Eli Lilly, Fujifilm, Johnson & Johnson, Kissei, Kowa, Kyowa Hakko Kirin, Medical Review, Medical View, Medscape Education, Medtronic Sofamor Danek, Mitsubishi Tanabe, MSD, Musashino Foods, Nipro, Novartis, Novo Nordisk, Ono, Sanofi, Sanwa Kagaku, Sumitomo Dainippon, Taisho, Takeda and Terumo, and has been in endowed chair from Asahi Mutual Life Insurance, Boehringer Ingelheim, Kowa, Mitsubishi Tanabe, MSD, Novo Nordisk, Ono and Takeda. TO, AS, MS, EAON, SSE, and KDK are current employees of MSD K.K. or Merck Sharp & Dohme Corp., subsidiaries of Merck & Co., Inc., Kenilworth, New Jersey, and may own stock/stock options in Merck & Co., Inc., Kenilworth, New Jersey. No other potential conflicts of interest relevant to this article are reported.

© 2021 Merck sharp & Dohme Corp. a subsidiary of Merck & Co., Inc., Kenitworth, N.J., U.S.A. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

Figures

FIGURE 1

Patient disposition. †This adverse event (AE) is not included in the summary AE table because it started during the placebo run‐in period

FIGURE 2

Time course of glycated haemoglobin (HbA1c) change from baseline