Abstract 59: The Effects of Dapagliflozin on Cardiovascular Risk Factors in Patients with Type 2 Diabetes Mellitus

Abstract

Background: Patients with type 2 diabetes mellitus (T2DM) often have multiple cardiovascular (CV) risk factors and, thus, an increased CV risk. Dapagliflozin (DAPA), a selective SGLT2 inhibitor currently under evaluation for the treatment of T2DM, reduces hyperglycemia by promoting renal glucose excretion, independently of insulin secretion or action. Methods: Using prospective exploratory analysis, the effects of DAPA on CV risk factors, including body weight, waist circumference, blood pressure (BP), plasma lipids, uric acid, estimated glomerular filtration rate (eGFR), and hypoglycemia were evaluated in four phase 3 studies. Patients were randomized to DAPA 2.5, 5, or 10 mg or placebo (PBO) once daily for 24 weeks as monotherapy in drug-naïve patients (Study 1, NCT00528372 , N=485 [main cohort n=274]), as add-on to metformin (Study 2, NCT00528879 , N=546), as add-on to glimepiride (Study 3, NCT00680745 , N=596), or as add-on to insulin (Study 4, NCT0067323, N=808). Non-protocol antidiabetic and weight-reducing drugs were prohibited; other background medications were not controlled. Mean changes from baseline to week 24 adjusted for baseline values were analyzed. Results: DAPA significantly reduced glycated hemoglobin in all studies (Table). Weight loss with DAPA was greater than with PBO in all 4 studies, with statistically significant differences in Studies 2, 3, and 4 ( P <0.0001). There were numerical decreases in waist circumference with DAPA in all 4 studies. DAPA reduced systolic BP and to a lesser extent, diastolic BP in all studies. Patients treated with DAPA showed inconsistent changes in triglycerides or LDL-cholesterol, whereas there were consistent increases in HDL-cholesterol. Decreases in serum uric acid were observed with DAPA in all studies. No clinically meaningful changes in eGFR were observed. Hypoglycemic events were infrequent and occurred in a similar proportion of patients in PBO and DAPA groups in Studies 1 and 2, but were more frequent with DAPA than with PBO in Studies 3 and 4, when added to sulfonylurea or insulin therapy. Conclusions: DAPA has favorable effects on important CV risk factors in patients with T2DM.