Efficacy and safety of canagliflozin in subjects with type 2 diabetes: systematic review and meta-analysis
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To assess the efficacy and safety of the novel sodium glucose co-transporter 2 (SGLT2) inhibitor—canagliflozin for type 2 diabetes (T2DM).
A search of Medline (1946–January 2014), Embase (1950–January 2014), and The Cochrane Library for randomized controlled trials of canagliflozin compared to placebo or active comparator in T2DM was performed. Clinical Trials website and unpublished U.S. Food and Drug Administration data were also searched.
Ten trials including 6,701 patients were analyzed. Compared with placebo, canagliflozin produced absolute reductions in glycated hemoglobin A1c levels when used as monotherapy (weighted mean difference (WMD) −1.08 %, 95 % confidence interval (CI) [−1.25 to −0.90], p < 0.00001) or add-on treatment (WMD −0.73 %, 95 %CI [−0.84 to −0.61], p < 0.00001). When compared with other active comparators, canagliflozin significantly reduced HbA1c by −0.21 % (WMD, 95 %CI [−0.33 to −0.08], p = 0.001). Canagliflozin led to greater body weight loss (vs. placebo, WMD −2.81 kg, 95 %CI [−3.26 to −2.37]; vs. active comparators, WMD −3.49 kg, 95 %CI [−4.86 to −2.12]). Hypoglycemia with canagliflozin was similar to placebo or sitagliptin, and was lower than glimepiride (risk ratio (RR) 0.15, 95 %CI [0.10 to 0.22]). Genital tract infections were more common with canagliflozin (vs. placebo, RR 3.76, 95 %CI [2.23 to 6.35]; vs. active comparators, RR 4.95, 95 %CI [3.25 to 7.52]). Similar incidences of urinary tract infections were noted with canagliflozin compared with control groups.
Canagliflozin led to improvements in reducing glycated hemoglobin A1c levels and body weight with low risk of hypoglycemia in patients with T2DM. Common adverse effects including genital tract infections and osmotic diuresis-related AEs were identified and reviewed. Risks of cardiovascular events are even less certain, and more data on long-term effects are needed.
KeywordsCanagliflozin Sodium glucose co-transporter 2 inhibitor Type 2 diabetes Systematic review
Conflict of interest
The authors have nothing to disclose
- 1.Danaei G, Finucane MM, Lu Y et al (2011) National, regional, and global trends in fasting plasma glucose and diabetes prevalence since 1980: systematic analysis of health examination surveys and epidemiological studies with 370 country-years and 2.7 million participants. Lancet 378(9785):31–40CrossRefPubMedGoogle Scholar
- 2.Inzucchi SE, Bergenstal RM, Buse JB et al (2012) Management of hyperglycemia in type 2 diabetes: a patient-centered approach. Position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care 35(6):1364–1379PubMedCentralCrossRefPubMedGoogle Scholar
- 9.FDA advisory committee recommends approval of canagliflozin for treatment of adults with type 2 diabetes. 2013.Available from: http://www.fda.gov/ newsevents/newsroom/pressannouncements/ ucm345848. htm [Last accessed 28 October 2013]
- 13.Clar C, Gill JA, Court R et al (2012) Systematic review of SGLT2 receptor inhibitors in dual or triple therapy in type 2 diabetes. BMJ Open 2(5). [PMC3488745]Google Scholar
- 15.Higgins JPT, Green S (2011) Cochrane handbook for systematic reviews of interventions. The Cochrane CollaborationGoogle Scholar
- 16.Review Manager (RevMan) [Computer program] (2012) Version 5.2. Copenhagen: The Nordic Cochrane Centre, The Cochrane CollaborationGoogle Scholar
- 22.Janssen Research & Development LLC. The CANTATA-MP Trial (CANagliflozin Treatment and Trial Analysis - Metformin and Pioglitazone). (NCT01106690). ClinicalTrials.gov Web site. [Last accessed 28 October 2013]Google Scholar
- 25.Schernthaner G, Gross JL, Rosenstock J et al (2013) Canagliflozin compared with sitagliptin for patients with type 2 diabetes who do not have adequate glycemic control with metformin plus sulfonylurea: a 52-week randomized trial. Diabetes Care 36(9):2508–2515PubMedCentralCrossRefPubMedGoogle Scholar
- 26.Cefalu WT, Leiter LA, Yoon KH et al (2013) Efficacy and safety of canagliflozin versus glimepiride in patients with type 2 diabetes inadequately controlled with metformin (CANTATA-SU): 52 weeks results from a randomised, double-blind, phase 3 non-inferiority trial. Lancet 382(9896):941–950CrossRefPubMedGoogle Scholar
- 30.Sha S, Devineni D, Ghosh A et al (2011) Canagliflozin, a novel inhibitor of sodium glucose co-transporter 2, dose dependently reduces calculated renal threshold for glu-cose excretion and increases urinary glu-cose excretion in healthy subjects. Diabetes Obes Metab 13:669–672CrossRefPubMedGoogle Scholar
- 36.U.S. Food and Drug Administration. FDA Briefing Document. NDA204042. Invokana (Canagliflozin) Tablets. Rockville, MD: U.S. Food and Drug Administration; 2013. Accessed at www.fda.gov/downloads/Advisory Committees/ Committees Meeting Materials/Drugs/Endo-crinologic and Metabolic Drugs Advisory Committee /UCM334550.pdf on 24 January 2013
- 37.Cardiovascular disease risk factors. World Heart Federation 2014; http:// www.world-heart-federation.org/cardiovascular-health/cardiovascular-disease- risk- factors/ (Last accessed on 12 January 2014)
- 38.Janssen Research & Development, LLC. A Randomized, Multicenter, Double-Blind, Parallel, Placebo-Controlled Study of the Effects of JNJ-28431754 on Cardiovascular Outcomes in Adult Subjects With Type 2 Diabetes Mellitus ClinicalTrials.gov Web site. (Last accessed on 12 January 2014)Google Scholar