Abstract 12429: Reductions in Mean 24-Hour Ambulatory Blood Pressure After 6-Week Treatment of Canagliflozin in Patients With Type 2 Diabetes Mellitus and Hypertension
Background: Canagliflozin (CANA), a sodium glucose co-transporter 2 inhibitor, decreases renal glucose reabsorption and increases urinary glucose excretion. In 26-wk clinical studies consistent and sustained reductions in BP have been observed. This study used ABPM to assess reduction of BP after the initiation of CANA.
Methods: In this 6-wk, placebo (PBO)-controlled study, 169 pts (mean [SD] age 58.6 [8.4] y, A1C 8.1% [0.9], seated SBP 138.5 mmHg [9.6], seated DBP 82.7 mmHg [8.1]), on 1-3 antihyperglycemic agents (required metformin; excluded insulin) and 1-3 antihypertensive agents (required ACEi or ARB; excluded loop diuretics) received ≥1 dose of the study medication (CANA 100 mg [n = 57], CANA 300 mg [n = 56], or PBO [n = 56]). Primary endpoint was change from baseline to Wk 6 (LOCF) in mean 24-hr SBP between CANA 300 mg and PBO. Primary efficacy analysis was based on an ANCOVA model which included terms for treatment and beta-blocker use and baseline mean 24-hr SBP as a covariate. Key secondary endpoints included change from baseline in mean 24-hr DBP, and mean day- and nighttime SBP and DBP for CANA 100 and 300 mg.
Results: At Wk 6, CANA 300 mg provided greater reductions in mean 24-hr SBP vs PBO (-4.9 mmHg, p = 0.006, Fig.). Reductions in mean 24-hr SBP were also observed with CANA 100 mg (-3.3 mmHg) vs PBO. Reductions in mean 24-hr DBP were observed for both CANA 100 mg (-1.94 mmHg) and CANA 300 mg (-2.92 mmHg*) vs PBO. CANA 100 and 300 mg resulted in greater reductions in mean daytime SBP (PBO-adjusted changes -4.0 mmHg* and -5.4 mmHg*) and DBP (PBO-adjusted changes -2.2 mmHg* and -3.0 mmHg*). Higher incidences of orthostasis, volume depletion and osmotic diuresis adverse events were observed with CANA 300 mg vs CANA 100 mg and PBO.
Conclusion: At Wk 6, CANA 300 mg provided a rapid and significant reduction in mean 24-hr SBP. Both CANA doses reduced daytime SBP and DBP, and demonstrated an overall safety profile consistent with clinical studies.
*nominal p value (p < 0.05)
Author Disclosures: R. Townsend: Consultant/Advisory Board; Modest; Medtronic, Janssen, GSK, Merck. Other; Modest; UpToDate. I. Machin: None. J. Ren: Employment; Significant; Janssen Pharmaceuticals, Inc. A. Trujillo: Employment; Significant; Janssen Pharmaceuticals, Inc. M. Kawaguchi: Honoraria; Modest; Mitsubishi Tanabe Pharmaceutical Company. U. Vijapurkar: Employment; Significant; Janssen Research & Development, LLC. M. Pfeifer: Employment; Significant; Janssen Pharmaceuticals, Inc..
- © 2015 by American Heart Association, Inc.