Combination therapy with insulin glargine plus metformin but not insulin glargine plus sulfonylurea provides similar glycemic control to triple oral combination therapy in patients with type 2 diabetes uncontrolled with dual oral agent therapy

Aims: Evaluate substituting insulin glargine (GLAR) for a thiazolidinedione (LLD) versus adding a third oral antidiabetes drug (OAD) in patients with uncontrolled type 2 diabetes mellitus (T2DM) on TZD + metformin or TZD + sulfonylurea. Methods: In this multicenter, open-label study, 337 T2DM patients with a glycated hemoglobin A(1c) (A1C) of 7.5-12.0% despite 3 months of treatment with a 170 plus metformin or a sulfonylurea were randomized to a third OAD (30AD; metformin or glyburide) or GLAR + 1 OAD (metformin or sulfonylurea) with TZD cessation, titrated to a fasting blood glucose 94 mg/dL. Results: Substitution of GLAR for a TZD led to an adjusted mean A1C change from baseline of 1.66% versus 1.86% in the 30AD arm (adjusted mean difference 0.20 [95% confidence interval, -0.11, 0.51], not meeting the noninferiority criteria). This difference was driven by the GLAR + sulfonylurea stratum. GLAR + metformin was as effective as 30AD in achieving glycemic control but with greater improvements in lipid parameters, less weight gain, and lower hypoglycemia rates. Conclusions: These findings favor substitution of GLAR for a TZD in T2DM patients not controlled on TZD + metformin. GLAR + sulfonylurea was less effective at lowering A1C than 30AD and not associated with the benefits observed with GLAR + metformin. (C) 2015 Published by Elsevier Inc.