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Efficacy and Safety of Canagliflozin in Type 2 Diabetes Patients of Different Ethnicity.

ABSTRACT: OBJECTIVE:To assess the efficacy and safety of the sodium glucose co-transporter 2 (SGLT2) inhibitor canagliflozin in patients of different ethnicities. DESIGN SETTING AND PATIENTS:Post hoc analysis of data pooled from four randomized, placebo-controlled, phase 3 studies of adults with inadequately controlled type 2 diabetes mellitus (T2DM). INTERVENTIONS:Once daily oral canagliflozin 100 mg or 300 mg, or placebo. MAIN OUTCOME MEASURES:Efficacy endpoints included change from baseline in HbA1c, body weight (BW), systolic blood pressure (SBP), and lipids at week 26; safety and tolerability were assessed by adverse event reports. RESULTS:Of the 2,313 patients included in this pooled analysis, 609 self-identified as Hispanic/Latino. Hispanic/Latino patients had a mean age of 54 years, mean duration of T2DM of 7 years, mean HbA1c of 8.1%, mean body mass index of 31.2 kg/m(2), and mean SBP of 126.1 mm Hg. There were more women in the non-Hispanic/Latino cohort (63%) compared with the Hispanic/Latino cohort. Placebo-subtracted changes in HbA1c were -.82% with canagliflozin 100 mg and -.94% with canagliflozin 300 mg in the Hispanic/Latino cohort, which were similar to reductions observed in the non-Hispanic/Latino cohort. Significantly greater dose-related reductions in HbA1c, BW, and SBP were observed with both canagliflozin doses compared with placebo. Canagliflozin was generally well-tolerated. Genital mycotic infections were less frequent in Hispanic/Latino women than in non-Hispanic/Latino women. CONCLUSIONS:The SGLT2 inhibitor canagliflozin was generally well-tolerated and was associated with clinically meaningful reductions in HbA1c, BW, and SBP in both Hispanic/Latino and non-Hispanic/Latino patients with T2DM.

SUBMITTER: Davidson JA

PROVIDER: S-EPMC4836903 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature

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Efficacy and Safety of Canagliflozin in Type 2 Diabetes Patients of Different Ethnicity.

Davidson Jaime A JA Aguilar Richard R Lavalle González Fernando J FJ Trujillo Angelina A Alba Maria M Vijapurkar Ujjwala U Meininger Gary G

Ethnicity & disease 20160421 2

<h4>Objective</h4>To assess the efficacy and safety of the sodium glucose co-transporter 2 (SGLT2) inhibitor canagliflozin in patients of different ethnicities.<h4>Design setting and patients</h4>Post hoc analysis of data pooled from four randomized, placebo-controlled, phase 3 studies of adults with inadequately controlled type 2 diabetes mellitus (T2DM).<h4>Interventions</h4>Once daily oral canagliflozin 100 mg or 300 mg, or placebo.<h4>Main outcome measures</h4>Efficacy endpoints included cha ...[more]

PMID: 27103773

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Project description:BackgroundCanagliflozin is a new SGLT2 inhibitor which has been approved as an adjunct to diet and exercise for the treatment of adults with type 2 diabetes (T2D) mellitus in more than 30 countries. To evaluate the efficacy and safety of canagliflozin in patients with T2D, we carried out a meta-analysis of phase III clinical trials to offer an additional evidence of the efficacy and safety of canagliflozin for evidence-based clinical practice, strictly restricting the treatment durations to 26 weeks (core period) and 52 weeks (extension period).MethodsRandomized controlled trials (RCTs) published in English were searched in PubMed, Embase, and the Cochrane Library database (before April 2016). The studies reporting the efficacy and safety of canagliflozin in patients with T2DM were considered. Two authors separately performed data extraction. The differences were discussed and resolved. Pooled weighted mean differences (WMDs) or relative risks and 95% confidence intervals (CIs) were computed by using either fixed- or random-effects models.ResultsAt the end of the selection process, 7 RCTs were collected and included in the present analysis. Placebo-subtracted WMDs (%) of glycosylated hemoglobin (HbA1c) were -0.63 (95% CI: -0.77, -0.49) and -0.80 (95% CI: -0.98, -0.62) for canagliflozin 100 and 300 mg, respectively, from baseline to week 26. At week 26, canagliflozin 100 and 300 mg significantly reduced the body weight from baseline when compared with that of placebo, with a WMD of -2.23 and -3.00 in percent changes (P < 0.001 for both). The fasting and postmeal glucose, blood pressure (BP), and triglycerides were also reduced. These reductions were sustained over 52 weeks but had no significant differences between the 100 and 300 mg doses. The overall safety of canagliflozin was good, with the exception of high incidence of genital mycotic infections and osmotic diuresis-related adverse events.ConclusionCanagliflozin was found to reduce HbA1c, fasting and postmeal glucose, body weight, BP, and triglycerides, and it was generally well tolerated in patients with T2DM.

Project description:IntroductionCanagliflozin is a sodium glucose co-transporter 2 inhibitor approved worldwide for the treatment of patients with type 2 diabetes mellitus (T2DM). The present study evaluated pharmacokinetics, pharmacodynamics, and safety of canagliflozin in Japanese patients with T2DM.MethodsCanagliflozin, at doses of 25, 100, 200, or 400 mg, was administered as a single dose and, after a washout of 1 day, in repeated doses for 14 consecutive days to 61 subjects in a randomized, double-blind, placebo-controlled study. Plasma concentrations of canagliflozin and urinary glucose excretion (UGE) were measured, and renal threshold for glucose excretion (RTG) was calculated. Safety was evaluated on the basis of adverse event (AE) reports, blood and urine laboratory parameters, and vital signs.ResultsPlasma canagliflozin maximum concentration and area under the concentration-time curve (AUC) values increased in a dose-dependent manner with the time to maximum concentration (t max) of 1.0 h and elimination half-life (t 1/2) of 10.22-13.26 h on Day 1. No significant changes in t max and t 1/2 were observed after multiple-dose administration. The linearity factors, as calculated from the ratios of AUC0-24h on Day 16 to AUC0-∞ on Day 1, were close to 1 in all canagliflozin groups. Canagliflozin increased UGE0-24h (80-110 g/day with canagliflozin ≥100 mg) and decreased RTG from the first day of treatment; these effects were sustained during the entire period of multiple administration. No significant AEs were noted. Urine volume was slightly increased on Day 1, but subsequent changes after repeated doses for 14 days were small. Urinary sodium tended to be higher in the early treatment period, whereas no particular change was observed in serum osmolality and hematocrit.ConclusionCanagliflozin increased UGE, decreased RTG, and was well tolerated throughout the entire period of multiple administrations in Japanese patients with T2DM.FundingMitsubishi Tanabe Pharma Corporation.Trial registrationClinicalTrials.gov#NCT00707954.

Project description:IntroductionThe efficacy and safety of canagliflozin, a sodium glucose co-transporter 2 (SGLT2) inhibitor, was evaluated in patients with type 2 diabetes mellitus (T2DM) inadequately controlled on sulfonylurea monotherapy.MethodsThe CANagliflozin cardioVascular Assessment Study (CANVAS) is a double-blind, placebo-controlled cardiovascular outcomes study that randomized participants to placebo or canagliflozin 100 or 300 mg once daily in addition to routine therapy. Participants in the CANVAS trial are men and women aged ≥30 years with T2DM and a history or high risk of cardiovascular disease, and inadequate glycemic control (glycated hemoglobin [HbA1c] ≥7.0% and ≤10.5%) on current antihyperglycemic therapies. The primary objective of this prespecified substudy was to assess change from baseline to 18 weeks in HbA1c among patients on sulfonylurea monotherapy.ResultsOf the 4330 patients enrolled in CANVAS, 127 met the entry criteria for the sulfonylurea monotherapy substudy (placebo, n = 45; canagliflozin 100 mg, n = 42; canagliflozin 300 mg, n = 40). At 18 weeks, placebo-subtracted changes (95% confidence interval) in HbA1c were -0.74% (-1.15, -0.33; P < 0.001) and -0.83% (-1.24, -0.42; P < 0.001) with canagliflozin 100 and 300 mg, respectively. Relative to placebo, canagliflozin 100 and 300 mg also decreased fasting plasma glucose (FPG; -2.1 mmol/L [-3.0, -1.2] and -2.7 mmol/L [-3.6, -1.7], respectively). Body weight was lower with canagliflozin 300 mg (-1.8% [-3.2, -0.4]; P = 0.014) but unchanged with canagliflozin 100 mg (-0.4% [-1.8, 1.0]; P = 0.557). Canagliflozin 300 mg increased hypoglycemia episodes compared to canagliflozin 100 mg and placebo (15%, 0%, and 4.4%, respectively). Adverse events (AEs) of male and female genital mycotic infections, pollakiuria, and thirst were more common with canagliflozin.ConclusionsCanagliflozin added to ongoing sulfonylurea monotherapy produced improvements in HbA1c, FPG, and body weight, with an increased incidence of AEs consistent with the mechanism of action of SGLT2 inhibition.FundingJanssen Research & Development, LLC.Clinical trial registrationClinicalTrials.gov NCT01032629.

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Efficacy and Safety of Canagliflozin in Type 2 Diabetes Patients of Different Ethnicity.

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Efficacy and Safety of Canagliflozin in Type 2 Diabetes Patients of Different Ethnicity.

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