Introduction
Methods
Study | Details | No. of patients included in analyses; dapagliflozin dose | Patient population |
---|---|---|---|
Variable selection phase | |||
Randomized, multicenter, 52-week, double-blind, active-controlled non-inferiority [8] | Dapagliflozin vs. glipizide as add-on to metformin | 400; dapagliflozin 2.5–10 mg (titration) | Men, women ≥18 years, HbA1c >6.5 to ≤10%, inadequately controlled with metformin and oral hypoglycemic drugs |
Model generation phase | |||
Randomized, multicenter, 24-week, double-blind active-controlled (two studies) [10] | Study 1, dapagliflozin 5 mg + metformin XR, dapagliflozin 5 mg + placebo, metformin XR + placebo Study 2, dapagliflozin 10 mg + metformin XR, dapagliflozin 10 mg + placebo, metformin XR + placebo | Both studies combined: 814. 405; dapagliflozin 5 or 10 mg. 409; metformin plus placebo | Men, women 18–77 years, HbA1c 7.5–12%, treatment naïve, exclusion NYHA class III, IV |
Validation phase | |||
Dapagliflozin 2.5, 5, or 10 mg vs. placebo | 399; dapagliflozin 5 or 10 mg (N = 265) | Men, women 18–77 years, HbA1c 7–10%, inadequately controlled with metformin, exclusion NYHA Class III, IV | |
Randomized, multicenter, 24-week, double-blind, parallel-group, placebo-controlled [26] | Dapagliflozin 1, 2.5 or 5 mg vs. placebo | 334; dapagliflozin 5 or 10 mg (N = 262) | Men, women 18–77 years, HbA1c ≥7 to ≤10%, treatment naïve, exclusion CVD or event in previous 6 months |
Randomized, multicenter, 24-week, double-blind, parallel-group, placebo-controlled [14] | Dapagliflozin 10 mg vs. placebo | 179; dapagliflozin 10 mg (N = 88) | Men, women 30–75 years, HbA1c 6.5–8.5%, inadequately controlled with metformin, 23.6% had previous CVD |
Randomized, multicenter, 24-week, double-blind, placebo-controlled [15] | Dapagliflozin 10 mg vs. placebo added to usual care | 899; dapagliflozin 10 mg (N = 448) | Men, women ≥45 years, HbA1c ≥7 to ≤10%, previously treated, documented CVD |
Randomized, multicenter, 24-week, double-blind, placebo-controlled [16] | Dapagliflozin 10 mg + sitagliptin vs. placebo + sitagliptin ± metformin | 446; dapagliflozin 10 mg (N = 223) | Men, women mean age 52.6–56.8 years, mean HbA1c 7.8–7.99%, previously treated |
Randomized, multicenter, 24-week double-blind, placebo-controlled [17] | Dapagliflozin 10 mg vs. placebo added to usual care | 945; dapagliflozin 10 mg (N = 474) | Men, women mean age 63.9 years, mean HbA1c 8%, previously treated, documented CVD |
Randomized, multicenter, 24-week (and 24-week extension), double-blind, placebo-controlled [18] | Dapagliflozin 5 or 10 mg + pioglitazone | 418; dapagliflozin 5 or 10 mg (N = 280) | Men, women ≥18 years, HbA1c ≥7 to ≤11%, either treatment naïve or previously treated, exclusion NYA class III, IV |
Randomized, multicenter, 24-week, double-blind, placebo-controlled, parallel-group international [9] | Dapagliflozin 2.5, 5 or 10 mg vs. placebo + open-label glimepiride | 435; dapagliflozin 5 or 10 mg (N = 292) | Men, women ≥18 years, HbA1c ≥7 to ≤10%, inadequately controlled with sulfonylurea, 30.5–38.7% had previous CVD |
Randomized, multicenter, 24-week (and 24-week extension), double-blind, placebo-controlled [19] | Dapagliflozin 2.5, 5 or 10 mg vs. placebo + open-label existing insulin ± ≤2 oral hypoglycemic drugs | 568; dapagliflozin 5 or 10 mg (N = 389) | Men, women 18–80 years, HbA1c ≥7.5 to ≤10.5%, inadequately controlled with insulin ± oral hypoglycemic drugs 47.4–52.1% had previous CVD (hypertension) |
Variable Selection
Model Generation
Variables selected |
---|
A. Baseline only
|
Glycated hemoglobin |
HOMA2 insulin sensitivitya
|
Fasting plasma glucose |
Duration T2DM (years) |
Proinsulin, fastinga
|
Glucose, urine concentration |
HOMA2 beta cell functiona
|
Creatinine |
LDL cholesterol (calculated), fasting |
Sex |
Cystatin C |
Race |
Ethnicitya
|
Glomerular filtration rate, calculated (MDRD equation) |
B. Baseline + week 3 change from baseline (LOCF)
|
Change from baseline in hemoglobin A1C (LOCF) |
Change from baseline in sitting heart rate (LOCF) |
Change from baseline in fasting plasma glucose (LOCF) |
Change from baseline in weight (LOCF) |
Baseline weight |
Baseline sitting heart rate |
Baseline CRP, high sensitivity fastinga
|
Baseline fatty acids, fasting free |