Combination Therapy With Exenatide Plus Pioglitazone Versus Basal/Bolus Insulin in Patients With Poorly Controlled Type 2 Diabetes on Sulfonylurea Plus Metformin: The Qatar Study.

OBJECTIVE: The Qatar Study was designed to examine the efficacy of combination therapy with exenatide plus pioglitazone versus basal/bolus insulin in patients with long-standing poorly controlled type 2 diabetes mellitus (T2DM) on metformin plus a sulfonylurea. RESEARCH DESIGN AND METHODS: The study randomized 231 patients with poorly controlled (HbA >7.5%, 58 mmol/mol) T2DM on a sulfonylurea plus metformin to receive ) pioglitazone plus weekly exenatide (combination therapy) or ) basal plus prandial insulin (insulin therapy) to maintain HbA <7.0% (53 mmol/mol). RESULTS: After a mean follow-up of 12 months, combination therapy caused a robust decrease in HbA from 10.0 ± 0.6% (86 ± 5.2 mmol/mol) at baseline to 6.1 ± 0.1% (43 ± 0.7 mmol/mol) compared with 7.1 ± 0.1% (54 ± 0.8 mmol/mol) in subjects receiving insulin therapy. Combination therapy was effective in lowering the HbA independent of sex, ethnicity, BMI, or baseline HbA. Subjects in the insulin therapy group experienced significantly greater weight gain and a threefold higher rate of hypoglycemia than patients in the combination therapy group. CONCLUSIONS: Combination exenatide/pioglitazone therapy is a very effective and safe therapeutic option in patients with long-standing poorly controlled T2DM on metformin plus a sulfonylurea.