Endocrine Abstracts

Background and aims: The efficacy and safety of dapagliflozin as add-on therapy in patients with type 2 diabetes mellitus (T2DM) and inadequate glycemic control with evogliptin and metformin combinations was investigated.

Materials and methods: Patients with HbA1c of 7.0% to 10.5% receiving evogliptin 5mg and metformin ≥1000 mg were randomized to receive dapagliflozin 10 mg/day (n=99) or placebo (n=99) for 24 weeks. The primary endpoint was change from baseline in HbA1c at week 24. Prespecified subgroup analyses of the change in HbA1c were performed in patients with screening HbA1c values<8%, ≥8%. Secondary endpoints were changes from baseline in 2hr-postprandial plasma glucose, body weight, uric acid, liver function and lipid parameters.

Results: HbA1c (baseline mean±SD: dapagliflozin 7.87±0.72%; placebo 7.77±0.68%) decreased significantly from baseline with dapagliflozin (placebo-subtracted least square [LS] mean change±SE: –0.70±0.11%, P<0.0001). In patients with higher screening HbA1c values (≥8%), placebo-subtracted LS mean decreases in HbA1c seen with dapagliflozin were numerically greater (–0.79±0.20% compared with –0.65±0.12% in patients with lower HbA1c values (<8%)). LS mean difference in 2hr-postprandial plasma glucose after breakfast at week 24 with dapagliflozin vs placebo was -27.48±7.63 mg/dl(P=0.0004). Significant reductions in uric acid and body weight were observed with dapagliflozin relative to placebo at week 24 [(LS mean difference± SE: -0.38±0.11 mg/dl (P=0.0007), -1.79±0.29 kg (P<0.0001), respectively). Compared to placebo, dapagliflozin treatment significantly reduced ALT, r-GT and hepatic steatosis index (HIS) at week 24 (placebo-subtracted LS mean change –2.77±1.37 U/l, P=0.0444; -9.46±3.56 U/l, P=0.0085; -0.91±0.33, P=0.0062). Patients receiving dapagliflozin showed placebo-subtracted LS mean increases in total and HDL cholesterol (6.73±2.82 mg/dl, P=0.0179; 2.78±0.87 mg/dl, P=0.0016, respectively). Adverse events occurred in 27.55% of patients receiving dapagliflozin and 27.27% receiving placebo. Adverse events were similar across treatment groups with a low overall risk of hypoglycemia (~3%).

Conclusions: Dapagliflozin improves hyperglycemia and fatty liver and well tolerated over 24 weeks as add-on to patients with type 2 diabetes inadequately controlled by metformin plus evogliptin combination.