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

Muhammad Abdul-Ghani, Osama Migahid, Ayman Megahed, John Adams, Curtis Triplitt, Ralph A DeFronzo, Mahmoud Zirie, Amin Jayyousi, Muhammad Abdul-Ghani, Osama Migahid, Ayman Megahed, John Adams, Curtis Triplitt, Ralph A DeFronzo, Mahmoud Zirie, Amin Jayyousi

Abstract

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 (HbA1c >7.5%, 58 mmol/mol) T2DM on a sulfonylurea plus metformin to receive 1) pioglitazone plus weekly exenatide (combination therapy) or 2) basal plus prandial insulin (insulin therapy) to maintain HbA1c <7.0% (53 mmol/mol).

Results: After a mean follow-up of 12 months, combination therapy caused a robust decrease in HbA1c 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 HbA1c independent of sex, ethnicity, BMI, or baseline HbA1c. 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.

Trial registration: ClinicalTrials.gov NCT02887625.

© 2017 by the American Diabetes Association.

Figures

Figure 1
Figure 1
Effect of combination therapy and insulin therapy on glycemic control. A: The change over time in the mean HbA1c is shown in subjects receiving combination therapy or insulin therapy. B: The percentage of subjects is shown in each treatment group achieving HbA1c <7.0% (53 mmol/mol) and 6.5% (48 mmol/mol). C: The change in HbA1c over time is shown in subjects in the combination therapy group stratified by baseline HbA1c into the upper 50% (n = 62) and lower 50% (n = 61). *P < 0.0001; **P = 0.001.
Figure 2
Figure 2
Effect of combination therapy and insulin therapy on FPG concentration (Conc.) (A) and postprandial plasma glucose concentration (B) in The Qatar Study. AB, after breakfast; AL, after lunch; AS, after supper; BL, before lunch; BS, before supper; BT, bedtime.
Figure 3
Figure 3
Effect of combination therapy and insulin therapy on body weight.

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