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


2. 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:

3. 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:

4. 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:

5. 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:

6. % 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:

7. 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:

8. 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:

9. 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:

10. 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:

11. 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: