Combination of the insulin sensitizer, pioglitazone, and the long-acting GLP-1 human analog, liraglutide, exerts potent synergistic glucose-lowering efficacy in severely diabetic ZDF rats.

Description

In order to measure the potentially additive roles of the peroxisome-proliferator activated receptor-g (PPAR-g) pioglitazone and the long acting glucagon-like protein-1 (GLP-1) analogue liraglutide on glycemic control, Larsen et al. randomized Zucker diabetic fatty rats to either a vehicle, pioglitazone (10 mg/kg/day), liraglutide (0.4 mg/kg/day), or to both pioglitazone and liraglutide. Both drugs improved glycemic control, as the HbA1c level achieved under treatment with these drugs was 4.8%. The HbA1c level achieved was 8.8% with liraglutide alone, 7.9% with pioglitazone alone, and 9.7% with vehicle. An oral glucose tolerance test was performed at the end of the trial. Similarly, the area under the curve of the glucose levels was considerably lower in rats treated with the combination of pioglitazone and liraglutide in comparison with the three other experimental conditions. Finally, pancreas histology analyses revealed that rats treated with the combination of pioglitazone and liraglutide showed more compact islets with less fibrosis and higher proportions of well-staining β-cells (for insulin). Based on these results, the authors concluded that before starting insulin treatment in severely diabetic patients, the combination of a GLP-1 analog with a TZD may warrant further consideration in clinical practice.