Oral antidiabetic drugs and cardiac remodeling

PhD ceremony: Ms. M. Yin, 16.15 uur, Academiegebouw, Broerstraat 5, Groningen

Dissertation: Oral antidiabetic drugs and cardiac remodeling

Promotor(s): prof. W.H. van Gilst

Faculty: Medical Sciences

Heart failure has severe end-stage symptoms and is associated with major morbidity and mortality, and health care costs. Diabetes and heart failure can affect, aggravate and provoke each other. Although pharmacological treatment has already achieved significant improvement, the outcome for heart failure patients is still poor. New therapeutic strategies on heart failure are therefore needed, especially in heart failure patients with diabetes. Clinical studies have demonstrated that some antidiabetic drugs play a beneficial role in cardiovascular system. In this thesis, we performed animal experiments and clinical evaluation to look into the effects of oral antidiabetic drugs on cardiac remodeling and heart failure. Our results indicated that metformin as a first line antidiabetic drug potentially attenuates heart failure development after myocardial infarction, in the absence of diabetes, and independent of systemic glucose levels and insulin intolerance. Vildagliptin is a new antidiabetic compound that was recently introduced in Europe. It can increase the endogenous incretin hormones by inhibition of their degradation. Long-term treatment with vildagliptin does not affect cardiac protection in a rat post-MI model of heart failure. Treatment with vildagliptin in Zucker diabetic fatty rats led to an improvement in cardiac fibrosis and myocardial metabolism resulting in improved cardiac diastolic function, independent from systemic glucose levels. In the clinical study, diabetes is associated with an increased incidence of non-ischemic heart failure in patients with coronary artery disease, and metformin treatment led a trend towards reduced heart failure hospitalisations in diabetic patients.