26 Chronic Saxagliptin Treatment in a Diabetic Rat Model Protects against Infarction Independently of its Glucose Lowering Capacity

The dipeptidyl peptidase-4 (DPP-4) inhibitor saxagliptin in combination with metformin has been suggested to significantly improve glycaemic control compared to either monotherapy in type 2 diabetes (T2D). In addition, metformin and other DPP-4 inhibitors have been shown to protect against ischemic injury in clinical and experimental studies. We therefore hypothesised that chronic treatment with saxagliptin monotherapy may protect the T2D heart against myocardial infarction. Moreover, in combination with metformin, an enhanced effect may be achieved. Goto-Kakizaki (GK-a model of T2D) rats received, via oral gavage, either saxagliptin (30 mg/kg/day), metformin (300 mg/kg/day),metformin & saxagliptin (300 mg/kg/day & 30 mg/kg/day) or vehicle (water) for 2 weeks. Blood glucose was measured before and throughout the treatment. Rats were subjected in vivo to 30min ischaemia/120min reperfusion. The infarct was quantified using TTC staining and expressed as a percentage of the myocardium at risk (I/R%). Both saxagliptin and metformin alone reduced myocardial infarct size (I/R%: 24.7 ± 1.4% with saxagliptin, 18.7 ± 2.5% with metformin, versus 44.6 ± 2.2% with vehicle; P