Table 1.
Study design and patient populations of studies evaluating canagliflozin and cardiovascular risk factors
| Study | Design | Treatment | Population characteristics | Endpoints evaluated |
|---|---|---|---|---|
| CANVAS14 | 2 years, MC, DB, R, PCT | CAN 300 mg, 100 mg, or PBO daily | n=4,330 Mean age =63.5 years HbA1c =7%–10.5% Mean duration of T2DM =13.4 years >30 years of age with ASCVD history or >50 years of age with >2 CV risk factors |
Primary: change in risk of CVD; safety and tolerability Secondary: change from baseline in beta-cell function, HbA1c, FPG, BW, BP, FPL, and side effects |
| CANVAS-R25 | 18 months, MC, DB, R, PCT | Initial: CAN 100 mg or PBO daily; Week 13 optional increase: CAN 300 mg or PBO daily | n=5,812 Mean age =64.0 years HbA1c =7%–10.5% Mean duration of T2DM =13.4 years eGFR >30 mL/min/1.72 m2 |
Primary: progression of albuminuria Secondary: composite outcome of hospitalization for HF or CV death |
| CANTATA-M7 | 26 weeks, DB, PCT | CAN 300 mg, 100 mg, or PBO daily | n=678 Mean age =52.4 years HbA1c =7%–10% or >10%–12% Mean duration of T2DM =4.6 years |
Primary: change from baseline in HbA1c Secondary: achievement of HbA1c <7.0%; change from baseline in FPG, SBP, BW, HDL-C |
| Townsend et al17 | 6 weeks, MC, DB, R, PCT | CAN 300 mg, 100 mg, or PBO daily | n=171 Mean age =58.6 years HbA1c >7%–10% Mean duration of T2DM =9 years HTN = SBP >130 mmHg, DBP >70 mmHg |
Primary: change from baseline in the mean 24-hour SBP Secondary: change from baseline in mean 24-hour DBP, daytime SBP and DBP, FPG, and BW |
| Wilding et al25 | 26 weeks, R, DB, PCT | CAN 300 mg, 100 mg, or PBO daily | n=469 Mean age =56.8 years HbA1c =7%–10.5% Mean duration of T2DM = 9.6 years Receiving M ET >1,500 mg per day for >8 weeks |
Primary: change from baseline in HbA1c by week 26 Secondary: change from baseline in HbA1c by week 52; achievement of HbA1c <7.0%; change from baseline in FPG, BW, HDL-C, and TG |
| Yale et al18 | 52 weeks, R, DB, PCT | CAN 300 mg, 100 mg, or PBO once daily | n=272 Mean age =68.5 years HbA1c 7%–10.5% Mean duration of T2DM =16.3 years CKD Stage 3 eGFR 30–50 mL/min/1.73 m2 |
Primary: change from baseline in HbA1c by week 26 Secondary: achievement of HbA1c <7.0% by week 26; change from baseline in FPG, BP, BW, and FPL |
| Lavalle- Gonzalez et al21 | 26 week core study period with 26 weeks extension, R, DB, PBO, and active- controlled | CAN 300 mg, 100 mg, PBO, or SITA 100 mg once daily | n=1,284 Mean age =55.4 years HbA1c =7%–10.5% Mean duration of T2DM =6.9 years |
Primary: change from baseline in HbA1c Secondary: achievement of proportion HbA1c <7.0%; change from baseline in FPG, SBP, BW, TG, and HDL-C |
| Schernthaner et al22 | 52 weeks, R, DB, active-controlled | CAN 300 mg or SITA 100 mg | n=756 Mean age =56.7 years HbA1c =7%–10.5% Receiving MET >1,500 mg per day for >8 weeks |
Primary: change from baseline in HbA1c Secondary: achievement of HbA1c <7.0%; change from baseline in FPG, SBP, DBP, BW, TG, and HDL-C |
| Forst et al23 | 52 weeks, R, DB, PBO, and active- controlled trial | CAN 300 mg, 100 mg, PBO, or SITA 100 mg | n=342 Mean age =57.4 years HbA1c =7%–10.5% Mean duration of T2DM =10.5 years |
Primary: change from baseline in HbA1c at week 26 Secondary: change from baseline in HbA1c at week 52; achievement of HbA1c <7.0%; change from baseline in FPG, SBP, beta-cell function; percent change in BW, HDL-C, and TG |
| Rosenstock et al24 | 12 weeks, MC, R, DB, PBO, and active-controlled | CAN 50 mg, 100 mg, 200 mg, 300 mg once daily or 300 mg twice daily, PBO, or SITA 100 mg | n=451 Mean age =52.9 years HbA1c 7%–10.5% Mean duration of T2DM = 6.0 years Receiving M ET >1,500 mg per day for >8 weeks |
Primary: change from baseline in HbA1c Secondary: achievement of HbA1c <7.0%; change from baseline in FPG, BW, overnight urinary glucose to creatinine ratio |
| Patorno et al16 | Retrospective cohort | CAN 300 mg, 100 mg, or active control of DPP4 inhibitor, GLP-agonist, or sulfonylurea | n=224,999 Mean age =56.4 years Mean HbA1c =8.8% |
Primary: hospitalization for HF; composite CV endpoint (hospitalization for acute MI, ischemic stroke, hemorrhagic stroke) Secondary: unstable angina, coronary revascularization, and individual components of CV events |
| CVD-REAL15 | Retrospective cohort | SGLT2 inhibitor (canagliflozin, empagliflozin, or dapagliflozin) or other oral or injectable glucose lowering agent | n=262,339 (including 132,572 canagliflozin) Mean age =57.0 years T2DM |
Primary: hospitalization for HF Secondary: all-cause mortality; composite of hospitalization for HF |
| CANDLE49 | 24 week, MC, R, DB, active controlled | CAN 100 mg, or GLIM 0.5 mg to 6 mg | n=250 HbA1c =7%–10.5% CHF: NYHA class I to III |
Primary: percent change from baseline in NT-proBNP Secondary: changes from baseline in HbA1c, SBP, DBP, BW, QoL, echocardiogram, and renal function |
Abbreviations: ASCVD, Atherosclerotic Cardiovascular Disease; BP, blood pressure; BW, body weight; CAN, canagliflozin; CHF, chronic heart failure; CKD, chronic kidney disease; CV, cardiovascular; DB, double blind; DBP, diastolic blood pressure; eGFR, estimated glomerular filtration rate; FPG, fasting plasma glucose; FPL, fasting plasma lipid; GLIM, glimepiride; HDL-C, high-density lipoprotein cholesterol; HF, heart failure; HTN, hypertension; MC, multi-center; MET, metformin; MI, myocardial infarction; NT-proBNP, N-terminal pro-brain natriuretic peptide; NYHA, New York Heart Association; PBO, placebo; PCT, placebo-controlled trial; QoL, quality of life; R, randomized; SBP, systolic blood pressure; SITA, sitagliptin; T2DM, type 2 diabetes mellitus; TG, triglyceride.