Canagliflozin and BP

Studies of canagliflozin (both as monotherapy and as adjunctive therapy) have found that it reduces hemoglobin A1C (HbA1C) in patients with T2DM, with reductions ranging from 0.37 to 1.16%, as compared with placebo.11 When used as monotherapy in patients with T2DM, canagliflozin yielded dose-dependent reductions in systolic blood pressure (SBP) and diastolic blood pressure (DBP) after 26 weeks.12 It also was effective in reducing BP when used as add-on therapy, together with insulin and commonly used oral antidiabetic drugs such as metformin, sulfonylureas, and pioglitazone. For example, a one-year study found significant changes from baseline of -3.4/-2.5 mmHg and -3.7/-2.7 mmHg in patients taking 100mg and 300mg of canagliflozin, together with metformin and pioglitazone.13 Similar findings were obtained in another 52-week study of 100mg and 300mg of canagliflozin versus placebo as add-on therapy to metformin and sulfonylurea.14 A number of other studies yielded similar findings.15,16

Dapagliflozin and BP

Clinical studies of dapagliflozin, used either as monotherapy or in combination with other antidiabetic agents, have found it to be effective in reducing HbA1C and also in lowering weight.2 Several of these studies included, as secondary endpoints, the effects of dapagliflozin on office SBP and DBP. For example, one study compared dapagliflozin monotherapy to placebo in patients with T2DM and found reductions in office SBP and DBP of up to -5.7 and -3.3 mmHg respectively.7Dapagliflozin was also found efficacious in reducing BP when used adjunctively with other antidiabetic agents.2 A study of 808 patients with T2DM taking insulin, with or without other oral antidiabetic drugs, found significantly greater reductions in office SBP with dapagliflozin versus placebo.8 A meta-analysis of studies published up to 2013 found a mean reduction in office SBP of -3.78 mmHg with dapagliflozin.5

Most studies have investigated the impact of dapagliflozin on office BP. However, ambulatory BP monitoring (ABPM) is more accurate, due to the “white-coat effect” that patients sometimes experience in medical settings.2Two studies investigated ABPM, in dapagliflozin-treated patients with inadequate glycemic and BP control, despite treatment with both antidiabetic and antihypertensive agents. They found that the dapagliflozin group had significantly greater reductions in both office and 24-hour ABPM, as compared with placebo group.9,10  

Empagliflozin and BP

Studies of empagliflozin have found improvements from baseline in office SBP and DBP.2 For example, a 12-week study of empagliflozin monotherapy versus placebo in 547 patients with T2DM found significant changes in BP in patients taking 10, 25, and 50mg doses (-5.57/-3.57, -4.60/-3.35, and -5.21/-3.03 mmHg, respectively), and a nonsignificant reduction in the 5mg dose group.17 Similar findings were obtained in studies of empagliflozin as add-on therapy to other oral antidiabetic agents, with or without insulin.5,18

One study investigating the effect of empagliflozin on 24-hour ABPM in patients with T2DM and hypertension found significant reduction at 12 weeks in the mean 24-hour SBP and DBP, as compared to placebo.19