Effect of Vildagliptin Versus Dapagliflozin as Add on Therapy to Metformin on Cardiovascular Risk Factors in Egyptian Type II Diabetic Obese Patients: Potential Impact of Genetic Polymorphism

Diabetes mellitus (DM) is a metabolic disorder resulting from a defect in insulin secretion, insulin action, or both. It is characterized by chronic hyperglycemia and is associated with a heavy health burden and macrovascular complications.

Because of the associated microvascular and macrovascular disease, diabetes accounts for almost 14% of United States health care expenditures, at least one-half of which are related to complications such as myocardial infarction, stroke, end-stage renal disease, retinopathy, and foot ulcers .

Common conditions coexisting with T2DM (e.g., hypertension and dyslipidemia) are clear risk factors for atherosclerotic cardiovascular diseases (ASCVD). Numerous studies have shown the efficacy of controlling individual cardiovascular risk factors in preventing or slowing ASCVD in people with diabetes. Furthermore, there is evidence that measures of 10-year coronary heart disease (CHD) risk among U.S. adults with diabetes have improved significantly over the past decade and that ASCVD morbidity and mortality have decreased . Thus, cardiovascular risk factors should be systematically assessed at least annually in all patients with diabetes. These risk factors include duration of diabetes, obesity/overweight, hypertension, dyslipidemia, smoking, a family history of premature coronary disease, chronic kidney disease, and the presence of albuminuria. Modifiable abnormal risk factors should be treated as described in the guidelines .

The general goals of the treatment of DM are to provide glycemic control, avoid acute complications, prevent, or delay the appearance of chronic complications of the disease, and thus to improve the quality of life. The management of type 2 DM also includes managing conditions associated with T2DM, such as obesity, hypertension, dyslipidemia, and cardiovascular disease. Initial treatment of T2DM includes both pharmacologic and non-pharmacologic therapy (lifestyle modification) for all patients. First-line therapy depends on comorbidities, patient-centered treatment factors, and management needs and generally includes metformin and comprehensive lifestyle modification. Other medications such as sulfonylureas, Dipeptidyl-peptidase 4 (DPP-4) inhibitors, glucagon-like peptide 1 receptor agonists (GLP1), sodiumglucose cotransporter 2 inhibitors (SGLT2), are usually added to metformin based on glycemic needs for individuals with T2DM with or at high risk for ASCVDs, heart failure, and/or chronic kidney disease.

Metformin is effective, safe, inexpensive, and may reduce risk of cardiovascular events and death. In addition, metformin is available in an immediate-release form for twice-daily dosing or as an extended-release form that can be given once daily. The latest challenge to the place of metformin has come from the recent demonstration of substantial cardiovascular outcomes benefits with GLP-1 receptor agonists and SGLT2 inhibitors.