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

Diabetes Obes Metab. 2020 Dec;22(12):2287-2294. doi: 10.1111/dom.14153. Epub 2020 Sep 3.

Abstract

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.

Keywords: exenatide, insulin, pioglitazone, Qatar study, type 2 diabetes.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blood Glucose
  • Diabetes Mellitus, Type 2* / drug therapy
  • Drug Therapy, Combination
  • Exenatide / therapeutic use
  • Follow-Up Studies
  • Glycated Hemoglobin
  • Glycemic Control
  • Humans
  • Hypoglycemic Agents / therapeutic use
  • Insulin / therapeutic use
  • Pioglitazone / therapeutic use
  • Qatar
  • Treatment Outcome
  • Venoms / therapeutic use

Substances

  • Blood Glucose
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Insulin
  • Venoms
  • Exenatide
  • Pioglitazone