Effects of Dapagliflozin vs. Vildagliptin on the Lipid Profile of Patients With Uncontrolled Type 2 Diabetes

Background Type 2 diabetes (T2D) represents one of the most common metabolic disorders globally. Insulin resistance is a fundamental issue associated with the disorder, wherein cells in the adipose tissue, liver, and muscle resist the action of insulin, leading to dysregulation of glucose metabolism. T2D is a known, significant, and independent risk factor for the development and progression of dyslipidemia, a condition characterized by abnormal lipid levels in the blood. Inadequately controlled T2D can lead to dyslipidemia through various mechanisms. Dyslipidemia, i.e., alteration in the levels of plasma lipids typically characterized by increased levels of triglycerides (TGs), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and low levels of high-density lipoprotein cholesterol (HDL-C), is a significant and modifiable risk factor in the development of atherosclerotic cardiovascular disease (ASCVD). Materials and methods In this prospective, observational, parallel-group, open-label study, 383 patients of inadequately controlled T2D receiving metformin (500-2000 mg) were randomized to receive vildagliptin (group A) or dapagliflozin (group B) for a 24-week duration. We compared the effects of vildagliptin and dapagliflozin on hemoglobin A1c (HbA1c), fasting plasma glucose (FPG), and lipid profile at baseline and after 24 weeks of therapy. Results A total of 248 patients with T2D completed the follow-up for 24 weeks (mean age: 53.8±8.4 years, and the mean body mass index {BMI} was 25.0±3.4 kg/m²). From the baseline to 24 weeks, the HDL-C increased by 1.1 mg/dL in group A and by 3.17 (95% CI: 3.0-7.1) mg/dL in group B (p=0.03). A significant decrease in the mean LDL-C levels by 11.8 (95% CI: -2.10, -16.6) mg/dL was observed in group A, whereas an increase in the levels of mean LDL-C by 6.4 (95% CI: 6.1, 6.69) mg/dL in group B (p=0.03) was observed. There was no significant difference in the mean change from baseline in the HbA1c levels (-0.71 vs. -1.08, p=0.65) and in the levels of TC (p=0.87), TG (p=0.37), apolipoprotein A (p=0.986), apolipoprotein B (p=0.563), and lipoprotein(a) (p=0.767) between the vildagliptin and the dapagliflozin group after 24 weeks of therapy. Conclusions In conclusion, both vildagliptin (a DPP-4i) and dapagliflozin (an SGLT2i), when added to metformin, showed comparable efficacy in controlling plasma glucose in patients with inadequately controlled type 2 diabetes. However, they had differing effects on lipid profiles and body weight. Vildagliptin led to greater reductions in LDL-C, suggesting its preference in patients with elevated LDL-C levels. In contrast, dapagliflozin may be more suitable for obese patients with low HDL-C. Thus, adding either drug to metformin not only improves glycemic control (FPG and HbA1c) but also favorably influences lipid profiles, potentially reducing ASCVD risk in this population.