Canagliflozin's Immediate Effects on Blood Pressure Seen in Study

In the past year, research on sodium glucose co-transporter 2 (SGLT2) inhibitors has shown that these diabetes drugs have benefits beyond the ability to lower glycated hemoglobin (A1C), which helped canagliflozin become the first drug in the class to win FDA approval in March 2013.¹

The ability of canagliflozin and other SGLT2s to control blood pressure, reported in Evidence-Based Diabetes Management² and in published research, is allowing clinicians to reduce the use of diuretics and, in some cases, eliminate them.

Now, new findings show that canagliflozin not only lowers blood pressure, but it also works quickly. Results presented Tuesday at the American Heart Association Scientific Sessions showed that the drug reduced systolic blood pressure (SBP) after just 6 weeks of treatment.³

The findings were presented during Tuesday’s poster session at AHA, which is being held in Orlando, Florida. The study involved both the 100 mg and 300 mg doses of canagliflozin.

Study methods. In a 6-week trial, 169 patients with a mean age of 58.6 years were started on the study drug. At baseline, average A1C was 8.1%, seated SBP was 138.5 mm Hg, seated DBP was 82.7; patients were background agents; all were taking metformin but none were taking insulin. Loop diuretics were excluded.

Patients were randomized to take either 100 mg or 300 mg doses of canagliflozin or placebo. On Day 1 of the study, patients’ seated BP, seated heart rate, and standing BP were measured. These measures were taken on Day 2, at the start of Week 3 and at Week 6 in the clinic.

In addition, ambulatory blood pressure measures were taken over a 24-hour period every 20 minutes during the daytime and every 30 minutes at night at 3 points during the study.

Results. At week 6, patients taking the 300 mg dose showed the greatest mean reduction in 24-hour ambulatory SPB compared with placebo; there was a mean difference of -4.9 mm Hg (6.2 mm Hg for 300 mg vs 1.2 mm Hg for placebo). Reductions were also seen for patients taking the 100 mg dose (3.3 mm Hg vs 1.2 mm Hg). Both groups taking the study drug also saw a reduction in 24-hour mean DBP after 6 weeks compared with placebo (differences of -3.2 mm Hg for the 300 mg dose and -2.2 mm Hg for the 100 mg dose, respectively).³

In addition, reductions in mean 24-hour SBP and DBP were seen as early as the Day 2, after patients took the first doses of the study drug.

Raymond Townsend, MD, of the University of Pennsylvania and the study’s lead author, told The American Journal of the Managed Care that the positive benefits of canagliflozin, and the SGLT2 class generally, come from the unique mechanism of action: this class works by expelling glucose through urination, which also helps patients lose weight. Townsend said canagliflozin does not disrupt potassium levels that could result in hypokalemia.

Nurses who have previously spoken with The American Journal of Managed Care say they find the SGLT2 class easy to use in clinical practice because it is compatible with other drugs that may be added to a regimen. Because patients know it offers a weight loss benefit, adherence is better than some other diabetes medications.

The study is timely, since the need to control blood pressure has been a major theme of the AHA meeting. Although the participants did not have diabetes, the SPRINT trial (Systolic Blood Pressure Intervention Trial) showed major benefits for keeping systolic blood pressure around 120 mm Hg for patients age 50 and above with other risk factors.⁴

Canagliflozin is marketed by Janssen Pharmaceutica as Invokana, which supported the study.

References

1. US FDA approves INVOKANA (canagliflozin) for the treatment of adults with type 2 diabetes [press release]. Raritan, NJ: Johnson and Johnson News; March 29, 2013. http://www.jnj.com/news/all/us-fda-approves-invokana-canagliflozin-for-the-treatment-of-adults-with-type-2-diabetes

2. Smith A. Studies showing SGLT2s also help control hypertension, eliminate some side effects. Am J Manag Care. 2015;21(SP5)SP154-155.

3. Townsend R, Machin I, Jen Ren J. Reductions in mean 24-hour ambulatory blood pressure after 6-week treatment of canagliflozin in patients with type 2 diabetes mellitus and hypertension. Presented at the American Heart Association Scientific Sessions; Orlando, Florida, November 10, 2015; abstract T 2095.

4. Whelton PK. Systolic Blood Pressure Intervention Trial (SPRINT). Presented at the American Heart Association Scientific Sessions; Orlando, Florida; November 9, 2015; abstract 23696.