Glimepiride versus pioglitazone combination therapy in subjects with type 2 diabetes inadequately controlled on metformin monotherapy: results of a randomized clinical trial

Objective: To compare the effect of add-on glimepiride or pioglitazone in subjects with type 2 diabetes inadequately controlled on metformin monotherapy. Research design and methods: Multicenter, randomized, parallel-group, open-label, forced-titration study involving 203 adults with poorly controlled type 2 diabetes (A1C 7.5-10%) on metformin monotherapy. Subjects were randomized to receive glimepiride or pioglitazone, titrated to the maximum dose for 26 weeks. Subjects were evaluated for A1C changes, fasting plasma glucose (FPG), insulin, C-peptide, and lipid levels. Safety outcomes and diabetes-related healthcare resource utilization were also evaluated. Results: Both treatment groups achieved similar and significant mean decreases from baseline to endpoint (week 26) in A1C (p = 0.0001) and FPG (p < 0.05). Glimepiride therapy, however, resulted in a more rapid decline in A1C levels at weeks 6, 12, and 20 vs. pioglitazone (p < 0.05). A mean A1C <= 7% was reached faster in the glimepiride group (median, 80-90 days vs. 140-150 days [p = 0.024]). Total and LDL cholesterol were significantly higher with pioglitazone treatment than with glimepiride at endpoint (p < 0.05). Glimepiride treatment was associated with an increased risk of hypoglycemia and pioglitazone with higher rate of peripheral edema. Healthcare resource utilization was similar between groups, but total healthcare costs were significantly lower for glimepiride versus pioglitazone over the course of the study, driven largely by drug costs. The use of fasting C-peptide concentration >= 0.27 nmol/L in the inclusion criteria was a potential limitation as it may have included those patients with an improved probability for glimepiride or pioglitazone response. In addition, a larger patient population would have provided a greater degree of data applicability. Conclusions: In patients with type 2 diabetes inadequately controlled on metformin monotherapy, add-on glimepiride or pioglitazone results in similar overall improvements in glycemic control. Compared with pioglitazone, glimepiride is associated with faster glycemic control, lower total and LDL cholesterol levels and reduced short-term healthcare costs.