OBJECTIVE: This 12-week study assessed the efficacy and tolerability of imeglimin as add-on therapy to the dipeptidyl peptidase-4 inhibitor sitagliptin in patients with type 2 diabetes inadequately controlled with sitagliptin monotherapy. RESEARCH DESIGN AND METHODS: In a multicenter, randomized, double-blind, placebo-controlled, parallel-group study, imeglimin (1,500 mg b.i.d.) or placebo was added to sitagliptin (100 mg q.d.) over 12weeks in 170 patientswith type 2 diabetes (mean age 56.8 years; BMI 32.2 kg/m2) that was inadequately controlled with sitagliptin alone (A1C ≥7.5%) during a 12-week run-in period. The primary ef ficacy end point was the change in A1C from baseline versus placebo; secondary end points included corresponding changes in fasting plasma glucose (FPG) levels, strati fication by baseline A1C, and percentage of A1C responders. RESULTS: Imeglimin reduced A1C levels (least-squares mean difference) from baseline (8.5%) by 0.60% compared with an increase of 0.12% with placebo (between-group difference 0.72%, P < 0.001). The corresponding changes in FPG were -0.93 mmol/L with imeglimin vs. -0.11 mmol/L with placebo (P = 0.014). With imeglimin, the A1C level decreased by ≥0.5% in 54.3% of subjects vs. 21.6% with placebo (P < 0.001), and 19.8%of subjects receiving imeglimin achieved a decrease in A1C level of ≤7% compared with subjects receiving placebo (1.1%) (P = 0.004). Imeglimin was generally well tolerated, with a safety pro file comparable to placebo and no related treatment-emergent adverse events. CONCLUSIONS: Imeglimin demonstrated incremental efficacy benefits as add-on therapy to sitagliptin, with comparable tolerability to placebo, highlighting the potential for imeglimin to complement other oral antihyperglycemic therapies.
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Supplementary Data: http://care.diabetesjournals.org/lookup/suppl/doi:10.2337/dc13-2349/-/DC1.