Achieving the composite endpoint of HbA1c, body weight, and systolic blood pressure reduction with canagliflozin in patients with type 2 diabetes

Abstract

Objective: In addition to achieving glycemic control, weight loss and blood pressure (BP) reduction are important components of type 2 diabetes mellitus (T2DM) management, as many patients with T2DM are overweight/obese and/or have hypertension. Canagliflozin, an SGLT2 inhibitor, has demonstrated improvements in HbA1c, body weight (BW), and systolic BP across a broad range of patients with T2DM. This analysis evaluated achievement of composite endpoints of HbA1c, BW, and systolic BP targets with canagliflozin versus placebo.

Methods: This post hoc analysis evaluated the proportion of T2DM patients achieving the composite endpoint of HbA1c reduction ≥0.5%, BW reduction ≥3%, and systolic BP reduction ≥4mmHg with canagliflozin 100 and 300mg compared with placebo using pooled data from four 26-week, phase 3 studies (N = 2313; NCT01081834, NCT01106677, NCT01106625, NCT01106690). The proportion of patients achieving the composite endpoint of HbA1c <7.0%, BW reduction ≥3%, and BP <130/80 mmHg was also evaluated.

Results: At week 26, greater proportions of patients met individual HbA1c, BW, and systolic BP targets with canagliflozin versus placebo. A greater proportion of patients treated with canagliflozin 100 or 300 mg versus placebo also achieved the composite endpoint of HbA1c reduction ≥0.5%, BW reduction ≥3%, and systolic BP reduction ≥4 mmHg at week 26 (21.1%, 25.3%, and 5.7%, respectively; odds ratios [95% CI] of 4.5 [3.1, 6.5] and 5.6 [3.8, 8.2]). A greater proportion of patients also achieved the composite endpoint of HbA1c <7.0%, BW reduction ≥3%, and BP <130/80 mmHg with canagliflozin 100 and 300 mg versus placebo (14.7%, 20.9%, and 3.3%, respectively; odds ratios [95% CI] of 5.2 [3.2, 8.4] and 8.4 [5.2, 13.5]). Canagliflozin was generally well tolerated, with a safety profile similar to that seen in other phase 3 studies.

Conclusions: Patients with T2DM were more likely to achieve clinically important reductions in HbA1c, BW, and systolic BP with canagliflozin versus placebo.

Keywords:

• Sodium glucose co-transporter 2 (SGLT2)
• canagliflozin
• type 2 diabetes mellitus (T2DM)
• blood glucose
• blood pressure
• body weight

Transparency

Declaration of funding

This study was supported by Janssen Scientific Affairs LLC. The sponsor was involved in the study design, data collection, data analysis, manuscript preparation, and publication decisions.

Author contributions: K.M. and D.I. contributed to the interpretation of data and drafting of the manuscript. M.J.D. and G.M. contributed to the design and conduct of the analysis/study; interpretation of data; and drafting of the manuscript. U.V. contributed to the analysis/interpretation of data and drafting of the manuscript. All authors approved the manuscript in its final form and agree to be accountable for aspects of the work.

Declaration of financial/other relationships

K.M., M.J.D., and D.I. have disclosed that they are full-time employees of Janssen Scientific Affairs LLC. U.V. and G.M. have disclosed that they are full-time employees of Janssen Research & Development LLC.

CMRO peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Acknowledgements

The authors thank all investigators, study teams and patients who were involved in these studies. Medical writing support was provided by Dana Tabor PhD and Alaina Mitsch PhD of MedErgy, and was funded by Janssen Scientific Affairs LLC. Canagliflozin has been developed by Janssen Research & Development LLC, in collaboration with Mitsubishi Tanabe Pharma Corporation.

Previous presentation: This data was previously presented, in part, at the 25th Annual Scientific and Clinical Congresses of the American Association of Clinical Endocrinologists (AACE), Orlando, FL, 25–29 May 2016; the American Association of Nurse Practitioners (AANP) 2016 National Conference, San Antonio, TX, 21–26 June 2016; 50th Annual Meeting of the Florida Society of Health-System Pharmacists (FSHP), Orlando, FL, 5–7 August 2016; and the 52nd Annual Meeting of the European Association for the Study of Diabetes (EASD), Munich, Germany, 12–16 September 2016.