Long-Term Efficacy of Dapagliflozin in T2DM Patients Receiving High-Dose Insulin John P.H. Wilding, DM, FRCP


Efficacy Outcome Measures At week 24 Primary efficacy outcome Change in HbA1c Secondary efficacy outcomes Change in total body weight Change in mean daily insulin dose Patients with mean daily insulin dose reductions ≥10% from baseline Change in fasting plasma glucose At week 48 Are changes seen at 24 weeks maintained? Wilding JPH, et al. Ann Intern Med. 2012;156:405-415.

Change in HbA1c at 24 and 48 Weeks Treatment 24 Weeks 48 Weeks Placebo + insulin Mean change from baseline (%) -0.39 -0.47 Dapagliflozin + insulin DAPA 2.5 mg Difference vs placebo (%) DAPA 5 mg DAPA 10 mg -0.79 -0.40* -0.89 -0.49* -0.96 -0.57* -0.32* -1.01 -0.54* *P <.001 Wilding JPH, et al. Ann Intern Med. 2012;156:405-415.

Change in Body Weight at 24 and 48 Weeks Treatment 24 Weeks 48 Weeks Placebo + insulin Mean change from baseline (kg) +0.43 +0.82 Dapagliflozin + insulin DAPA 2.5 mg Difference vs placebo (kg) DAPA 5 mg DAPA 10 mg -0.92 -1.35* -1.00 -1.42* -1.61 -2.04* -0.96 -1.78* -1.00* -1.82* -2.43* *P <.001 Wilding JPH, et al. Ann Intern Med. 2012;156:405-415.

Change in Daily Insulin Dose at 24 and 48 Weeks Treatment 24 Weeks 48 Weeks Placebo + insulin Mean change from baseline (U) +5.65 +10.54 Dapagliflozin + insulin DAPA 2.5 mg Difference vs placebo (U) DAPA 5 mg DAPA 10 mg -1.95 -7.60* -0.63 -6.28* -1.18 -6.82* -0.92 -11.46* +0.30 -10.24* -0.70 -11.25* *P <.001 Wilding JPH, et al. Ann Intern Med. 2012;156:405-415.

% Patients with Mean Daily Dose Reductions ≥ 10% from Baseline Treatment 24 Weeks 48 Weeks Placebo + insulin 10.2% 10.5% Dapagliflozin + insulin DAPA 2.5 mg Difference vs placebo DAPA 5 mg DAPA 10 mg +6.3% (P = .064) (P = .060) +8.9% (P = .013) +7.6% (P = .030) +7.0% (P = .041) +8.1% (P = .024) Wilding JPH, et al. Ann Intern Med. 2012;156:405-415.

Change in Fasting Plasma Glucose at 24 and 48 Weeks Treatment 24 Weeks 48 Weeks Dapagliflozin + insulin DAPA 2.5 mg Mean change from baseline (mmol/L) DAPA 5 mg DAPA 10 mg -0.65* -1.12* -1.10* -0.69* -0.90* -0.94* *P <.001) Wilding JPH, et al. Ann Intern Med. 2012; 156: 405-415.

Safety (% Patients) Treatment-related adverse events Placebo: 20.8% DAPA: 21.3% (2.5 mg); 29.2% (5 mg); 29.1% (10 mg) Serious adverse events Placebo: 13.2% DAPA: <13.4% ≥1 event of hypoglycemia Placebo: 51.8% DAPA: 60.4% (2.5 mg); 55.7% (5 mg); 53.6% (10 mg) Serious/severe hypoglycemia Placebo: 1 hypoglycemic coma DAPA: 2 patients in 5 mg group Wilding JPH, et al. Ann Intern Med. 2012;156:405-415.

Genital/Urinary Tract Infections Compared with placebo, a significantly greater % of patients receiving DAPA had events suggesting genital infection There was no significant difference between % of placebo and DAPA patients with events suggesting urinary tract infections Most suggestive events were mild to moderate and responded to routine treatment Wilding JPH, et al. Ann Intern Med. 2012;156:405-415.

Renal Effects DAPA  Urinary glucose, hematocrit, serum creatinine, blood urea nitrogen, and cystatin C levels  Serum uric acid levels and calculated creatinine Greater absolute changes in the dapagliflozin groups, compared with placebo These changes were not accompanied by increased rates of renal impairment or failure, hypotension, dehydration, or hypovolemia Wilding JPH, et al. Ann Intern Med. 2012;156:405-415.

Conclusions Compared with placebo + insulin, DAPA + insulin resulted in significant reductions from baseline in HbA1c, body weight, mean daily insulin dose, and fasting plasma glucose, and a significant increase in % patients with ≥10% decrease in daily insulin dose In comparison to a decrease in insulin dose in DAPA groups at 24 and 48 weeks, insulin requirement increased in placebo patients Benefits seen at 24 weeks were sustained or improved at 48 weeks, demonstrating that DAPA continues to work as long as the patient’s kidneys continue to function There was no kidney damage associated with DAPA in this study Genital/urinary infections were mild to moderate and managed with routine therapy DAPA + insulin is an appropriate choice for T2DM patients who have poor glycemic control on insulin, particularly those who are obese Wilding JPH, et al. Ann Intern Med. 2012; 156: 405-415.