Combination therapy with exenatide plus pioglitazone was safe and effective in patients with longstanding, poorly controlled type 2 diabetes who were on metformin plus a sulfonylurea, according to results of the Qatar study (Exenatide Plus Pioglitazone Versus Insulin in Poorly Controlled T2DM; ClinicalTrials.gov identifier: NCT02887625) published in Diabetes Care.
Researchers randomly assigned 231 adult patients who were on treatment with a sulfonylurea plus metformin to receive pioglitazone plus weekly exenatide (combination therapy; n = 123) or basal plus prandial insulin (insulin therapy; n = 108) to maintain a glycated hemoglobin (HbA1c) level <7% (53 mmol/mol). All patients had poorly controlled type 2 diabetes, which was defined as an HbA1c level >7.5% (58 mmol/mol).
Baseline characteristics including age, body mass index (BMI), and diabetes duration were comparable between groups.
One-year results indicated that combination therapy reduced HbA1c levels from 10±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 patients receiving insulin therapy. Results of the combination therapy were independent of sex, ethnicity, BMI, or baseline HbA1c level.
In addition, when compared with the combination therapy arm, patients receiving insulin therapy demonstrated significantly greater weight gain (4.2±1 kg vs 2.1±1.1 kg; P <.0001), as well as a nearly 3-fold higher incidence of hypoglycemic events (6.6 vs 2.3 per patient-year; P <.0001).
“The present results are impressive and, contrary to standard dogma, demonstrate that even in individuals with very poorly controlled, longstanding [type 2 diabetes], combination therapy with a [glucagon-like peptide-1 receptor agonist] plus pioglitazone can achieve nearly normal/normal HbA1c levels,” the researchers wrote. “We believe that the robust results observed in the current study should foster a larger multiethnic study with longer duration to validate the findings in the current study and examine their benefit on diabetic microvascular and macrovascular complications.”
Disclosure: Dr DeFronzo is on the advisory boards of AstraZeneca, Novo Nordisk, Janssen, Intarcia, and Boehringer-Ingelheim; receives research support from Bristol-Myers Squibb, Boehringer-Ingelheim, Takeda, and AstraZeneca; and is on the speaker’s bureaus of Novo-Nordisk and Astra Zeneca. AstraZeneca provided exenatide for this study.
- Abdul-Ghani M, Migahid O, Megahed A, et al. Combination therapy with exenatide plus pioglitazone versus basal/bolus insulin in poorly controlled patients with type 2 diabetes on sulfonylurea plus metformin: the Qatar study [published online January 17, 2017]. Diabetes Care. doi:10.2337/dc16-1738.