Safety and Tolerability of Canagliflozin in Patients With Type 2 Diabetes Mellitus: Pooled Analysis of Phase 3 Study Results

Usiskin, Keith; Kline, Irina; Fung, Albert; Mayer, Cristiana; Meininger, Gary

doi:10.3810/pgm.2014.05.2753

Cited by 87 publications

(183 citation statements)

References 31 publications

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“…Unlike the results of previous studies, canagliflozin was not associated with a higher incidence of genital mycotic infections, with no genital mycotic infections reported in males or females in either treatment group 27, 28…”

Section: Discussioncontrasting

confidence: 90%

Tolerability of canagliflozin in patients with type 2 diabetes mellitus fasting during Ramadan: Results of the Canagliflozin in Ramadan Tolerance Observational Study (CRATOS)

Hassanein

Echtay

Hassoun³

et al. 2017

Int J Clin Pract

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SummaryAimsThere is a large population of people with type 2 diabetes mellitus (T2DM) who are Muslim and fast during Ramadan. Changes in the pattern and amount of meal and fluid intake during Ramadan, in addition to the long fasting hours, may increase the risk of hypoglycaemia, hyperglycaemia, and dehydration. The Canagliflozin in Ramadan Tolerance Observational Study (CRATOS) evaluated the tolerability of canagliflozin, a sodium glucose co‐transporter 2 inhibitor, compared with sulphonylureas among patients with T2DM who fast during Ramadan.MethodsThis non‐randomised, parallel‐cohort, prospective, comparative, observational study was conducted in the Middle East during Ramadan and enrolled patients who were taking canagliflozin (n=162) or any sulphonylurea (n=159) added to metformin±dipeptidyl peptidase‐4 inhibitor. The proportion of patients who experienced hypoglycaemia events was assessed as the primary end‐point. Between‐cohort comparisons were adjusted using propensity score analysis.ResultsDuring Ramadan, fewer patients experienced symptomatic hypoglycaemia with canagliflozin vs sulphonylurea (adjusted odds ratio: 0.273 [95% CI: 0.104, 0.719]). Of hypoglycaemia events for which blood glucose was measured, two of six with canagliflozin and 27 of 37 with sulphonylurea were confirmed by blood glucose <3.9 mmol/L. More patients treated with canagliflozin experienced volume depletion events compared with sulphonylurea (adjusted odds ratio: 3.5 [95% CI: 1.3, 9.2]). Missed fasting days were few and medication adherence was high in both groups. No patients treated with canagliflozin and 9.4% treated with sulphonylurea adjusted their medication dose near the beginning of Ramadan. Both treatments were generally well tolerated, with low rates of adverse events and no serious adverse events in either group.ConclusionsOverall, these findings support the use of canagliflozin for the treatment of adults with T2DM who fast during Ramadan.ClinicalTrials.gov Identifier: NCT02737657

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Section: Discussioncontrasting

confidence: 90%

Tolerability of canagliflozin in patients with type 2 diabetes mellitus fasting during Ramadan: Results of the Canagliflozin in Ramadan Tolerance Observational Study (CRATOS)

Hassanein

Echtay

Hassoun³

et al. 2017

Int J Clin Pract

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“…4. In the pooled analysis of four placebo-controlled phase 3 trials (n = 2313) [72], treatment-related adverse events (AEs) occurred in up to 1.7-fold more canagliflozin 100 or 300 mg/day than placebo recipients over 26 weeks (20.5 and 22.9 vs. 13.2%) and, consistent with canagliflozin's mechanism of action (Sect. 2), the most common AEs associated with the drug were female genital mycotic infection (GMI) (10.4 and 11.4 vs. 3.2%), urinary tract infection (UTI) (5.9 and 4.3 vs. 4.0%), increased urination (5.3 and 4.6 vs. 0.8%) and male GMI (4.2 and 3.7 vs. 0.6%).…”

Section: Tolerabilitymentioning

confidence: 72%

“…GMIs in this analysis were never serious, rarely (<1% of patients) led to therapy discontinuation and responded to standard antifungal treatment [72], lasting a median of 7 and 18 days in treated female and male canagliflozin recipients [75].…”

Section: Draft Manuscript-confidential Not For Circulation To Third mentioning

confidence: 76%

“…2), the most common AEs associated with the drug were female genital mycotic infection (GMI) (10.4 and 11.4 vs. 3.2%), urinary tract infection (UTI) (5.9 and 4.3 vs. 4.0%), increased urination (5.3 and 4.6 vs. 0.8%) and male GMI (4.2 and 3.7 vs. 0.6%). AEs were generally mild or moderate and few patients experienced serious AEs (≈3% in each group) or death (<0.3% in each group) [72].…”

Section: Tolerabilitymentioning

confidence: 95%

“…included vulvovaginal mycotic infection in women (5.9 and 5.3 vs. 1.3% with placebo) and balantitis in men (2.2 and 1.7 vs. 0%) in the pooled analysis of four placebo-controlled studies [72]. GMIs in this analysis were never serious, rarely (<1% of patients) led to therapy discontinuation and responded to standard antifungal treatment [72], lasting a median of 7 and 18 days in treated female and male canagliflozin recipients [75].…”

Section: Draft Manuscript-confidential Not For Circulation To Third mentioning

confidence: 99%

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Canagliflozin: A Review in Type 2 Diabetes

Deeks

Scheen

2017

Drugs

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Canagliflozin (Invokana ® ) is a sodium-glucose co-transporter-2 (SGLT2) inhibitor indicated in various countries worldwide for the once-daily oral treatment of type 2 diabetes (T2D). Unlike many T2D therapies, canagliflozin lowers blood glucose levels independently of insulin, with the inhibition of SGLT2 reducing renal reabsorption of glucose and increasing excretion of glucose in the urine. In well-designed clinical trials, canagliflozin (as first-line monotherapy or add-on therapy to other antihyperglycaemic agents) improved glycaemic control in adults with T2D, including those of older age and/or at high cardiovascular (CV) risk, and also had beneficial effects on their bodyweight and BP; whether the drug impacts the CV risk profile of T2D is currently being evaluated in the large CV outcomes study CANVAS. Canagliflozin was generally well tolerated, had a low risk of hypoglycaemia and was most commonly associated with adverse events such as genital and urinary tract infections and increased urination, consistent with its mechanism of action. Thus, canagliflozin is a useful monotherapy and add-on therapy option for the management of T2D in adults, and its CV profile is eagerly awaited.

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Efficacy and Safety of Dapagliflozin in Men and Women With Heart Failure With Reduced Ejection Fraction

et al. 2021

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IMPORTANCEWomen may respond differently to certain treatments for heart failure (HF) with reduced ejection fraction (HFrEF) than men.OBJECTIVE To investigate the efficacy and safety of dapagliflozin compared with placebo in men and women with HFrEF enrolled in the Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure trial (DAPA-HF).DESIGN, SETTING, AND PARTICIPANTS Prespecified subgroup analysis of a phase 3 randomized clinical trial conducted at 410 sites in 20 countries. Patients with New York Heart Association functional class II through IV with an ejection fraction of 40% or less and elevated N-terminal pro-B-type natriuretic peptide were eligible. Data were analyzed between June 2020 and January 2021.INTERVENTIONS Addition of once-daily 10 mg of dapagliflozin or placebo to guideline-recommended therapy. MAIN OUTCOMES AND MEASURESThe primary outcome was the composite of an episode of worsening HF (HF hospitalization or urgent HF visit requiring intravenous therapy) or cardiovascular death.RESULTS A total of 4744 patients were randomized in DAPA-HF, of whom 1109 were women (23.4%). Compared with placebo, dapagliflozin reduced the risk of worsening HF events or cardiovascular death to a similar extent in both men and women (hazard ratios, 0.73 [95% CI, 0.63-0.85] and 0.79 [95% CI, 0.59-1.06], respectively; P for interaction = .67). Consistent benefits were observed for the components of the primary outcome and all-cause mortality. Compared with placebo, dapagliflozin increased the proportion of patients with a meaningful improvement in symptoms (Kansas City Cardiomyopathy Questionnaire total symptom score of Ն5 points; men, 59% vs 50%; women, 57% vs 54%; P for interaction = .14) and decreased the proportion with worsening symptoms (Kansas City Cardiomyopathy Questionnaire total symptom score decrease of Ն5 points; men, 25% vs 34%; women, 27% vs 31%; P for interaction = .15), irrespective of sex. Results were consistent for the Kansas City Cardiomyopathy Questionnaire clinical summary score and overall summary score. Study drug discontinuation and serious adverse events were not more frequent in the dapagliflozin group than in the placebo group in either men or women.CONCLUSIONS AND RELEVANCE Dapagliflozin reduced the risk of worsening HF, cardiovascular death, and all-cause death and improved symptoms, physical function, and health-related quality of life similarly in men and women with heart failure and reduced ejection fraction. In addition, dapagliflozin was safe and well-tolerated irrespective of sex.

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Safety and Tolerability of Canagliflozin in Patients With Type 2 Diabetes Mellitus: Pooled Analysis of Phase 3 Study Results

Abstract: Canagliflozin as monotherapy and as combination therapy was generally well tolerated in patients with T2DM inadequately controlled on their current diabetes mellitus treatment.

Cited by 87 publications

References 31 publications

Tolerability of canagliflozin in patients with type 2 diabetes mellitus fasting during Ramadan: Results of the Canagliflozin in Ramadan Tolerance Observational Study (CRATOS)

Tolerability of canagliflozin in patients with type 2 diabetes mellitus fasting during Ramadan: Results of the Canagliflozin in Ramadan Tolerance Observational Study (CRATOS)

Canagliflozin: A Review in Type 2 Diabetes

Efficacy and Safety of Dapagliflozin in Men and Women With Heart Failure With Reduced Ejection Fraction

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