Randomized clinical trial of the safety and efficacy of sitagliptin and metformin co-administered to Chinese patients with type 2 diabetes mellitus

Linong Ji, Ping Han, Xiaoyue Wang, Jingdong Liu, Shaoxiong Zheng, Ying-Ming Jou, Edward A O'Neill, Gregory T Golm, Samuel S Engel, Keith D Kaufman, R Ravi Shankar, Linong Ji, Ping Han, Xiaoyue Wang, Jingdong Liu, Shaoxiong Zheng, Ying-Ming Jou, Edward A O'Neill, Gregory T Golm, Samuel S Engel, Keith D Kaufman, R Ravi Shankar

Abstract

Introduction: The results of a clinical trial to evaluate the efficacy and safety of initial combination therapy with sitagliptin and metformin in Chinese patients with type 2 diabetes and inadequate glycemic control are reported here.

Materials and methods: This was a multicenter, randomized, double-blind, placebo-controlled, parallel group, 24-week clinical trial carried out in China. Patients (n = 744) with type 2 diabetes and inadequate glycemic control (glycated hemoglobin ≥7.5 and ≤11.0%) who were either drug-naïve or washed out of previous therapy were randomized in equal ratios to sitagliptin 100 mg once daily (q.d.; S100), metformin 500 mg twice daily (b.i.d.; M1000), metformin 850 mg b.i.d. (M1700), sitagliptin 50 mg b.i.d. plus metformin 500 mg b.i.d. (S100/M1000), sitagliptin 50 mg b.i.d. plus metformin 850 mg b.i.d. (S100/M1700), or placebo.

Results: The mean baseline glycated hemoglobin in randomized patients was 8.7%. Least squares mean changes from baseline in glycated hemoglobin were -0.59% (placebo), -0.99% (S100), -1.29% (M1000), -1.56% (M1700), -1.67% (S100/M1000) and -1.83% (S100/M1700) (P < 0.05 for each active group vs placebo, for S100/M1700 and S100/M1000 vs S100, and for S100/M1000 vs M1000). All treatments were generally well-tolerated. The overall incidence of hypoglycemia (symptomatic or asymptomatic) was higher in the two co-administration groups (S100/M1700 and S100/M1000) compared with the placebo. The incidence of symptomatic hypoglycemia was low, and similar, across all treatment groups. The incidences of gastrointestinal adverse events were generally higher in high-dose metformin groups than in the placebo group.

Conclusions: In Chinese patients with type 2 diabetes, initial combination therapy with sitagliptin and metformin was generally well-tolerated, and provided improvement in glycemic control.

Keywords: Dipeptidyl peptidase-4 inhibitor; Glycemic control; Incretin therapy.

© 2016 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.

Figures

Figure 1
Figure 1
Study design. AHA, antihyperglycemic agent; FFSG, fasting finger‐stick glucose; FPG, fasting plasma glucose; M1000, metformin 500 mg b.i.d.; M1700, metformin 850 mg b.i.d.; R, randomization; S, screening; S100, sitagliptin 100 mg q.d.; S100/M1000, sitagliptin/metformin 50/500 mg b.i.d.; S100/M1700, sitagliptin/metformin 50/850 mg b.i.d.; T2DM, type 2 diabetes mellitus; TZDs, thiazolidinediones.
Figure 2
Figure 2
Percentage of patients with glycated hemoglobin (HbA1c) ‡vs S100 P < 0.001; vs M1000 P = 0.007; *vs S100 P = 0.001; vs M1700 P = 0.007; †vs S100 P < 0.001; vs M1000 P = 0.005; ¥vs S100 P < 0.001; vs M1700 P = 0.002. Placebo (); S100 (); M1000 (); M1700 (); S100/M1000 (); S100/M1700 ().

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