Key result
Gemigliptin showed a dose-dependent protective effect on diabetic nephropathy, but its effect on cardiomyopathy was ambivalent, with the lower dose (0.04%) significantly attenuating left ventricular dysfunction and cardiac fibrosis while the higher dose (0.4%) did not.
Why the study?
The effects of long-term DPP-4 inhibition on micro- and macro-vascular complications in type 2 diabetes remain uncertain.
Does gemigliptin improve cardiovascular and renal complications in a rodent model of type 2 diabetes?
Does gemigliptin improve cardiovascular and renal complications in a rodent model of type 2 diabetes?
In a diabetic mouse model, a low dose of gemigliptin protected against diabetic cardiomyopathy, whereas a high glucose-lowering dose did not, highlighting potential dose-dependent and organ-specific effects of DPP-4 inhibitors.
May protect against diet-induced lethality and inflammation in diabetic mice; hypothesis-generating for human vascular complications.
OBJECTIVE: Although dipeptidyl peptidase-4 (DPP-4) inhibitors have been suggested to have a non-glucoregulatory protective effect in various tissues, the effects of long-term inhibition of DPP-4 on the micro- and macro-vascular complications of type 2 diabetes remain uncertain. The aim of the present study was to investigate the organ-specific protective effects of DPP-4 inhibitor in rodent model of type 2 diabetes. METHODS: Eight-week-old diabetic and obese db/db mice and controls (db/m mice) received vehicle or one of two doses of gemigliptin (0.04 and 0.4%) daily for 12 weeks. Urine albumin excretion and echocardiography measured at 20 weeks of age. Heart and kidney tissue were subjected to molecular analysis and immunohistochemical evaluation. RESULTS: Gemigliptin effectively suppressed plasma DPP-4 activation in db/db mice in a dose-dependent manner. The HbA1c level was normalized in the 0.4% gemigliptin, but not in the 0.04% gemigliptin group. Gemigliptin showed a dose-dependent protective effect on podocytes, anti-apoptotic and anti-oxidant effects in the diabetic kidney. However, the dose-dependent effect of gemigliptin on diabetic cardiomyopathy was ambivalent. The lower dose significantly attenuated left ventricular (LV) dysfunction, apoptosis, and cardiac fibrosis, but the higher dose could not protect the LV dysfunction and cardiac fibrosis. CONCLUSION: Gemigliptin exerted non-glucoregulatory protective effects on both diabetic nephropathy and cardiomyopathy. However, high-level inhibition of DPP-4 was associated with an organ-specific effect on cardiovascular complications in type 2 diabetes.
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Moon et al. (2016) studied Type 2 diabetes (animal model) (n=32). Gemigliptin vs. Vehicle (untreated db/db mice) was evaluated on Left ventricular end-diastolic dimension (LVEDD) in mm (p=<0.05). Gemigliptin showed a dose-dependent protective effect on diabetic nephropathy, but its effect on cardiomyopathy was ambivalent, with the lower dose (0.04%) significantly attenuating left ventricular dysfunction and cardiac fibrosis while the higher dose (0.4%) did not.
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