Abstract
BackgroundBlood glucose control is fundamental albeit not enough to prevent diabetic macrovascular complications. Dipeptidyl peptidase-4 (DPP-4) inhibitors are effective in improving metabolic parameters in patients with type 2 diabetes mellitus (T2DM) but little is known about its cardiovascular effects. We compared the DPP-4 inhibitor sitagliptin with bedtime NPH insulin (NPH) as add-on therapy in patients with T2DM, aiming to ascertain which drug would have additional cardioprotective effects.MethodsThirty-five T2DM patients inadequately controlled with metformin plus glyburide were randomized to receive sitagliptin (n = 18) or NPH (n = 17) for 24 weeks. Fasting plasma glucose, HbA1c, lipid profile, C-reactive protein, active glucagon-like peptide (aGLP-1) levels, 24-hour ambulatory blood pressure measurement and comprehensive 2-dimensional echocardiogram were determined before and after treatments.ResultsBoth sitagliptin and NPH therapies decreased HbA1c levels after 24 weeks. Fasting plasma glucose and triglyceride levels decreased in the NPH group whereas only sitagliptin increased aGLP-1 levels. Left ventricular diastolic dysfunction (LVDD) was detected in 58.6% of twenty-nine patients evaluated. Beneficial effects in LVDD were observed in 75% and 11% of patients treated with sitagliptin and NPH, respectively (p = 0.015). Neither therapy changed C-reactive protein or blood pressure.ConclusionsSitagliptin and bedtime NPH were similarly effective on glucose control. Improvement in LVDD in T2DM patients treated with sitagliptin was suggested, probably related to the increase of aGLP-1 levels. Therefore, DPP-4 inhibitor seems to have cardioprotective effects independent of glucose control and may have a role in the prevention of diabetic cardiomyopathy.
Highlights
Blood glucose control is fundamental albeit not enough to prevent diabetic macrovascular complications
At baseline, there were no significant differences between the two groups with respect to gender, age, duration of diabetes, weight, Body mass index (BMI), waist-hip ratio, FPG, HbA1c, C-reactive protein (CRP), aGLP-1, total and HDL-cholesterol levels
CRP, total-C and HDL-C levels did not change after 24 weeks of either therapy and remained similar between groups, whereas final LDL-C levels were lower in the SITA group in comparison to the NPH group (p = 0.019), this difference was already present at baseline
Summary
Blood glucose control is fundamental albeit not enough to prevent diabetic macrovascular complications. Dipeptidyl peptidase-4 (DPP-4) inhibitors are effective in improving metabolic parameters in patients with type 2 diabetes mellitus (T2DM) but little is known about its cardiovascular effects. Beta-cell dysfunction, insulin resistance and impaired suppression of glucagon are key pathologic defects in type 2 diabetes (T2DM), partially dependent on the reduced incretin effect [1,2]. In order to achieve appropriate control of diabetes, address those dysfunctions and prevent vascular complications, the Recently, incretin-based therapy with glucagon-like peptide 1 (GLP-1) analogues or dipeptidyl peptidase-4 (DPP-4) inhibitors, that increase GLP-1 levels, has been proposed as an alternative to currently available anti-hyperglycemic agents. DPP-4 inhibitors improve several cardiovascular risk factors They may lower blood pressure, improve renal and endothelial dysfunction and lipid levels and reduce inflammatory markers, oxidative stress and platelet aggregation in patients with T2DM. Are weight neutral and rarely cause hypoglycemia [2,4]
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