Sustained alogliptin elicits superior control of glycemia and related complications in diabetic rats: Effects on vital organs functions, biochemistry, and structure

Despite its efficacy in diabetes management, concerns about potential cardiovascular injury associated with alogliptin have limited its widespread use. This study investigated whether sustained, once-weekly low-dose alogliptin provides greater efficacy with fewer adverse effects than daily administration. Type 2 diabetes was induced in rats using a high-fructose, high-fat, high-salt diet for three weeks, followed by streptozotocin (STZ) injection. Diabetic rats were then allocated into three groups: diabetic, S Alogliptin (weekly administered sustained alogliptin preparation), and F Alogliptin (daily administered standard fast-acting alogliptin). Postprandial blood glucose levels and body weight were monitored. Cardiovascular hemodynamics, cardiac enzymes, lipid profile, HOMA-IR, oxidative stress, and quantitative histopathological changes in the ventricles, aorta, liver, and skeletal muscle were evaluated at study end. S alogliptin provided superior postprandial glycemic control over 40 days and improved metabolic parameters, including reduced bodyweight gain, triglycerides, HOMA-IR, and leptin, with increased adiponectin compared with F Alogliptin. More alleviation in cardiac dysfunction was observed in S alogliptin versus F alogliptin as manifested by reductions in cardiac enzymes, as well as improved hemodynamics (contractility index, pulse pressure, and dicrotic notch pressure). This was accompanied by more alleviation by S alogliptin in tissue inflammation and damage as evidenced by reductions in heart malondialdehyde (MDA) and histopathological examination of ventricles, aorta, liver, and skeletal muscles. CONCLUSION: Overall, S Alogliptin achieved superior glycemic control and greater mitigation of metabolic and cardiovascular complications of diabetes than F Alogliptin.