Dapagliflozin Add-On Therapy Improves Body Composition and Metabolic Parameters in Overweight Type 2 Diabetic Patients: A Pilot Study

Abstract

Background: Sodium-glucose cotransporter-2 inhibitors (SGLT2-i) inhibit renal glucose reabsorption in the proximal tubules, and reduce plasma glucose, body weight and cardiovascular risk in patients with type 2 diabetes mellitus (T2DM). The data on the effect of SGLT-2i on body composition are conflicting: in some reports, they reduce fat mass, while in other reports, they determine reduction of extra-and intra-cellular fluids. The aim of our pilot study was to investigate the body compartments changes and the effects on glycemia and plasma lipids of add-on SGLT2-i dapagliflozin therapy in poorly controlled overweight/obese T2DM patients. Methods: Fifty-six overweight (body mass index (BMI) > 25) uncontrolled (HbA1c > 53 mmol/mol; 7%) T2DM outpatients were recruited. They were treated with metformin and basal insulin (group A) or metformin (group B). Weight, BMI, waist circumference (WC), fasting blood glucose (FPG), HbA1c, plasma lipids, bioelectric parameters and derived body compartments (phase angle (pA), total body water (TBW), fat free mass (FFM) and fat mass (FM)) were assessed at baseline (T0) and after 16 weeks (T1) of dapagliflozin 10 mg add-on treatment. Student's t-test and one-way analysis of variance (ANOVA) were used to compare the T0 and T1 data. Results: After 16 weeks, all the patients had weight loss (-3.0 ± 0.6 kg, P < 0.0001) and reduced WC (-2.5 ± 0.6 cm, P < 0.0001). Weight reduction was significant in both groups separately (group A:-2.5 ± 0.3 kg, P ≤ 0.001; group B:-3.4 ± 0.4 kg, P ≤ 0.001) and was higher in group B. FFM was not impaired in group A (from 60.2 ± 5.2 to 59.5 ± 8.1 kg; ns) and in group B (from 60.4 ± 6.2 to 59.3 ± 6.6 kg; ns). FM decreased in all the patients (29.9 ± 6.84 kg vs. 26.30 ± 7.4 kg, P < 0.000); a higher reduction was found in group B (-3.6 ± 1.2 kg, P < 0.001) vs. group A (-2.3 ± 1.3 kg, P < 0.001). Metabolic control improved in all the patients: FPG 172 ± 49.4 mg/dL vs. 137 ± 36.8 mg/ dL at T1, P < 0.0001; HbA1c 69 ± 9.3 mmol/mol (8.5±1.5%) vs. 60 ± 8.7 mmol/mol (7.6±1.4%), P = 0.000. In group A, insulin dose was reduced by 9.3%. Cholesterol and triglycerides (TG) levels decreased in overall population (181.8 ± 48.8 mg/dL vs. 170.7 ± 40.7, P = 0.003; 172 ± 93 mg/dL vs. 143.2 ± 87.8, P = 0.000). Conclusions: Dapagliflozin add-on therapy induced weight loss and metabolic improvement in overweight and obese T2DM patients. Also insulin-treated patients had weight loss (2.5 kg). Bioelectric impedance analysis (BIA) demonstrated FM loss without FFM impairment and was confirmed to be a simple and effective method to assess body composition in clinical practice.