Canagliflozin is the first sodium-glucose cotransporter-2 (SGLT2) inhibitor to be approved for use in Canada. Canagliflozin is indicated for patients with type 2 diabetes to improve glycemic control as monotherapy or in combination with metformin; a sulfonylurea; metformin and a sulfonylurea; metformin and pioglitazone; or insulin (with or without metformin) when these drugs do not provide adequate glycemic control. The recommended starting dose is 100 mg once daily. A dose of 300 mg once daily may be considered for patients who have tolerated a dose of 100 mg once daily and who need tighter glycemic control, provided they have an estimated glomerular filtration rate (eGFR) of ≥ 60 mL/min/1.73 m² and have a low risk of adverse reactions associated with reduced intravascular volume. Canagliflozin is contraindicated in renally impaired patients who have an eGFR of less than 45 mL/min/1.73 m², have end-stage renal disease, or are on dialysis.

The current CADTH Common Drug Review (CDR) submission for canagliflozin is for use in combination with metformin and a sulfonylurea in adult patients with type 2 diabetes mellitus to improve glycemic control when diet, exercise, and dual therapy do not provide adequate glycemic control.

Contents

• Clinical Review Report
  • ABBREVIATIONS
  • EXECUTIVE SUMMARY
    • Introduction
    • Results and Interpretation
    • Conclusions
  • 1. INTRODUCTION
    • 1.1 Disease Prevalence and Incidence
    • 1.2 Standards of Therapy
    • 1.3 Drug
  • 2. OBJECTIVES AND METHODS
    • 2.1 Objectives
    • 2.2 Methods
  • 3. RESULTS
    • 3.1 Findings From the Literature
    • 3.2 Included Studies
    • 3.3 Patient Disposition
    • 3.4 Exposure to Study Treatments
    • 3.5 Critical Appraisal
    • 3.6 Efficacy
    • 3.7 Harms
  • 4. DISCUSSION
    • 4.1 Summary of Available Evidence
    • 4.2 Interpretation of Results
  • 5. CONCLUSIONS
  • APPENDIX 1 PATIENT INPUT SUMMARY
  • APPENDIX 2 LITERATURE SEARCH STRATEGY
  • APPENDIX 3 EXCLUDED STUDIES
  • APPENDIX 4 DETAILED OUTCOME DATA
  • APPENDIX 5 SUMMARY OF OTHER STUDIES
  • REFERENCES
• Pharmacoeconomic Review Report
  • ABBREVIATIONS
  • EXECUTIVE SUMMARY
    • Background
    • Summary of Identified Limitations and Key Results
    • Conclusions
  • 1. SUMMARY OF THE MANUFACTURER’S PHARMACOECONOMIC SUBMISSION
  • 2. MANUFACTURER’S BASE CASE
  • 3. SUMMARY OF MANUFACTURER’S SENSITIVITY ANALYSES
    • 3.1 Probabilistic Sensitivity Analysis
  • 4. LIMITATIONS OF MANUFACTURER’S SUBMISSION
    • 4.1 Variability in the Pricing of DPP-4 Inhibitors
    • 4.2 Choice of Comparators
    • 4.3 Unadjusted Indirect Comparison for Many Outcomes for the Canagliflozin 100 mg and Sitagliptin 100 mg Comparison
    • 4.4 Limitations With the Network Meta-analysis for Canagliflozin 100 mg and Sitagliptin 100 mg Comparison
    • 4.5 Disutility Value Associated With Weight Gain
    • 4.6 Estimation of Hypoglycemia Rates With Sitagliptin
  • 5. CADTH COMMON DRUG REVIEW ANALYSES
  • 6. PATIENT INPUT
  • 7. CONCLUSIONS
  • APPENDIX 1 COST COMPARISON
  • APPENDIX 2 SUMMARY OF KEY OUTCOMES
  • APPENDIX 3 ADDITIONAL INFORMATION
  • APPENDIX 4 SUMMARY OF OTHER HEALTH TECHNOLOGY ASSESSMENT REVIEWS OF DRUG
  • APPENDIX 5 REVIEWER WORKSHEETS
  • REFERENCES
• CDEC Final Recommendation
  • Recommendation
  • Reasons for the Recommendation
  • Background
  • Summary of CDEC Considerations
  • Other Discussion Points
  • Research Gaps

This review report was prepared by the Canadian Agency for Drugs and Technologies in Health (CADTH). In addition to CADTH staff, the review team included a clinical expert in endocrinology who provided input on the conduct of the review and the interpretation of findings.

Through the CADTH Common Drug Review (CDR) process, CADTH undertakes reviews of drug submissions, resubmissions, and requests for advice, and provides formulary listing recommendations to all Canadian publicly funded federal, provincial, and territorial drug plans, with the exception of Quebec.

The report contains an evidence-based clinical and/or pharmacoeconomic drug review, based on published and unpublished material, including manufacturer submissions; studies identified through independent, systematic literature searches; and patient-group submissions. In accordance with CDR Update — Issue 87, manufacturers may request that confidential information be redacted from the CDR Clinical and Pharmacoeconomic Review Reports.

The information in this report is intended to help Canadian health care decision-makers, health care professionals, health systems leaders, and policy-makers make well-informed decisions and thereby improve the quality of health care services. The information in this report should not be used as a substitute for the application of clinical judgment with respect to the care of a particular patient or other professional judgment in any decision-making process, nor is it intended to replace professional medical advice. While CADTH has taken care in the preparation of this document to ensure that its contents are accurate, complete, and up-to-date as of the date of publication, CADTH does not make any guarantee to that effect. CADTH is not responsible for the quality, currency, propriety, accuracy, or reasonableness of any statements, information, or conclusions contained in the source documentation. CADTH is not responsible for any errors or omissions or injury, loss, or damage arising from or relating to the use (or misuse) of any information, statements, or conclusions contained in or implied by the information in this document or in any of the source documentation.

This document is intended for use in the context of the Canadian health care system. Other health care systems are different; the issues and information related to the subject matter of this document may be different in other jurisdictions and, if used outside of Canada, it is at the user’s risk. This disclaimer and any questions or matters of any nature arising from or relating to the content or use (or misuse) of this document will be governed by and interpreted in accordance with the laws of the Province of Ontario and the laws of Canada applicable therein, and all proceedings shall be subject to the exclusive jurisdiction of the courts of the Province of Ontario, Canada.

CADTH takes sole responsibility for the final form and content of this document, subject to the limitations noted above. The statements and conclusions in this document are those of CADTH and not of its advisory committees and reviewers. The statements, conclusions, and views expressed herein do not necessarily represent the views of Health Canada or any Canadian provincial or territorial government. Production of this document is made possible by financial contributions from Health Canada and the governments of Alberta, British Columbia, Manitoba, New Brunswick, Newfoundland and Labrador, Northwest Territories, Nova Scotia, Nunavut, Ontario, Prince Edward Island, Saskatchewan, and Yukon.