Comparative evaluation of empagliflozin, canagliflozin and sitagliptin cardioprotective properties in rats with experimental type 2 diabetes mellitus

Background: Myocardial infarction (MI) is one of the leading causes of mortality in patients with type 2 diabetes mellitus (DM), therefore it is essential to give preference to a glucose-lowering drug having optimal cardioprotective properties. A comparative study of the various sodium-glucose co-transporter inhibitors representatives’ protective effects in experimental MI was not carried out within the framework of one study.

Aim: To evaluate the influence of empagliflozin (EMPA) and canagliflozin (CANA), in comparison with sitagliptin (SITA), on hemodynamic parameters and myocardial damage area in rats with diabetes type 2 model in experimental MI.

Materials and methods: Type 2 DM was modelled in Wistar rats by means of 4-week high-fat diet followed by nicotinamide 230 mg/kg and streptozotocin 60 mg/kg administration. 4 weeks after DM induction the following groups were made: «DM+SITA» — treatment with SITA 50 mg/kg, «DM+EMPA» — treatment with EMPA 2 mg/kg, «DM+CANA» — treatment with CANA 25 mg/kg per os once daily for 8 weeks. Animals in «DM» group remained untreated for the following 8 weeks. Rats in control group were fed with standard chow. 16 weeks after the experiment beginning transient global myocardial ischemia was modelled in all rats. Hemodynamic parameters and myocardium necrosis area were evaluated.

Results: The necrosis area was larger in «DM» group, than in control one (p=0.018). Infarction size in «DM+SITA» did not differ from that in «DM» group (62.92(41.29;75.84) and 57.26(45.51;70.08)%, р=0.554). Necrosis area in «DM+EMPA» and «DM+CANA» groups was smaller than in «DM» group (37.90(20.76;54.66)%, 46.15(29.77;50.55) vs 57.26(45.51;70.08)%, р=0.008 and р=0.009, respectively). Necrosis size did not differ between «DM+EMPA» and «DM+CANA» groups (p=0.630). Ischemic contracture in «DM+CANA» group was less prominent than under the use of all other glucose-lowering drugs. We observed increase of coronary blood flow in «DM+EMPA» group, in comparison with «DM», «DM+CANA» and «DM+SITA» groups.

Conclusions: SITA does not have cardioprotective effect in ischemia-reperfusion injury in diabetic rats. EMPA and CANA have similarly prominent infarct-limiting properties. EMPA is able to increase coronary blood flow, whereas cardioprotective action of CANA is associated with ischemic contracture diminishing.

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