Combination therapy with pioglitazone/exenatide improves beta‐cell function and produces superior glycaemic control compared with basal/bolus insulin in poorly controlled type 2 diabetes: A 3‐ year follow‐up of the Qatar study

Aim To examine the long‐term efficacy of thiazolidinedione plus a glucagon‐like peptide‐1 receptor agonist versus basal‐bolus insulin on glycaemic control and beta‐cell function in patients with poorly controlled type 2 diabetes (T2D) on metformin plus sulphonylurea. Materials and Methods Three hundred and thirty‐one patients with poorly controlled T2D were recruited over 3 years and were followed for an additional year. Subjects received a 75 g oral glucose tolerance test (OGTT) at baseline and at study end. After completing the baseline OGTT, subjects were randomized to receive either pioglitazone plus weekly exenatide (combination therapy) or basal/bolus insulin (insulin therapy) to maintain an HbA1c of less than 7.0%. The primary outcome of the study was the difference in HbA1c at study end between the two treatment groups. Results Both therapies caused a robust decrease in HbA1c. However, combination therapy caused a greater decrement (−1.1%, P  < .0001) than insulin therapy, and more subjects in the combination therapy group (86%) achieved the American Diabetes Association goal of glycaemic control (HbA1c < 7.0%) than those in the insulin therapy group (44%) ( P < .0001). Both therapies improved insulin secretion. However, the improvement in insulin secretion with combination therapy was 2.5‐fold greater ( P  < .001) than with insulin therapy (50%). Insulin therapy caused more weight gain and hypoglycaemia. Conclusion Both combination therapy and insulin therapy effectively reduced HbA1c in poorly controlled T2D on multiple oral agents. However, combination therapy produced a greater improvement in insulin secretion and decrease in HbA1c with a lower risk of hypoglycaemia.