(HealthDay News) — Treatment escalation options have different efficacy following failure of exenatide or glimepiride added to metformin in patients with type 2 diabetes, according to a study published in Diabetes, Obesity and Metabolism.

Guntram Schernthaner, MD, from Rudolfstiftung Hospital in Vienna, and colleagues assessed third-line thiazolidinedione (TZD) or glimepiride therapy in 144 patients inadequately controlled on metformin plus exenatide twice daily, and third-line exenatide twice daily in 166 patients inadequately controlled on metformin plus glimepiride. 

The authors assessed changes in HbA1c, BMI, lipids, hypoglycemia and vital signs.

The researchers found that add-on TZD decreased HbA1c significantly better than add-on glimepiride among patients inadequately controlled on metformin plus exenatide (130-week difference, 0.48%; P=.001), but there were significant increases in BMI and systolic blood pressure (BP). 

For add-on glimepiride to add-on thiazolidinedione, the ratio of documented systolic hypoglycemia rates was 8.48 (P<.0001). There was a significant reduction in HbA1c and BMI at 130 weeks with add-on exenatide after metformin plu glimepiride, with an increased rate of documented symptomatic hypoglycemia from metformin plus limepiride (ratio, 1.49).

“Future studies should examine various other potential treatment combinations, doses, and sequences to help define optimal triple therapy,” the researchers wrote.

The study was funded by Amylin and Eli Lilly. Several authors and editors disclosed financial ties to these companies as well as Bristol-Myers Squibb and Astra Zeneca.


  1. Schernthaner G et al. Diabetes Obes Metab. 2015;doi:10.1111/dom.12471.