Dataset Information

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.

ABSTRACT: To evaluate the efficacy and safety of canagliflozin, a sodium glucose cotransporter 2 inhibitor, compared with sitagliptin in subjects with type 2 diabetes inadequately controlled with metformin plus sulfonylurea.In this 52-week, randomized, double-blind, active-controlled, phase 3 study, subjects using stable metformin plus sulfonylurea (N = 755) received canagliflozin 300 mg or sitagliptin 100 mg daily. Primary end point was change from baseline in A1C at 52 weeks. Secondary end points included change in fasting plasma glucose (FPG) and systolic blood pressure (BP), and percent change in body weight, triglycerides, and HDL cholesterol. Safety was assessed based on adverse event (AE) reports.At 52 weeks, canagliflozin 300 mg demonstrated noninferiority and, in a subsequent assessment, showed superiority to sitagliptin 100 mg in reducing A1C (-1.03% [-11.3 mmol/mol] and -0.66% [-7.2 mmol/mol], respectively; least squares mean difference between groups, -0.37% [95% CI, -0.50 to -0.25] or -4.0 mmol/mol [-5.5 to -2.7]). Greater reductions in FPG, body weight, and systolic BP were observed with canagliflozin versus sitagliptin (P < 0.001). Overall AE rates were similar with canagliflozin (76.7%) and sitagliptin (77.5%); incidence of serious AEs and AE-related discontinuations was low for both groups. Higher incidences of genital mycotic infections and osmotic diuresis-related AEs were observed with canagliflozin, which led to one discontinuation. Hypoglycemia rates were similar in both groups.Findings suggest that canagliflozin may be a new therapeutic tool providing better improvement in glycemic control and body weight reduction than sitagliptin, but with increased genital infections in subjects with type 2 diabetes using metformin plus sulfonylurea.

SUBMITTER: Schernthaner G

PROVIDER: S-EPMC3747923 | biostudies-literature | 2013 Sep

REPOSITORIES: biostudies-literature

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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.

Schernthaner Guntram G Gross Jorge L JL Rosenstock Julio J Guarisco Michael M Fu Min M Yee Jacqueline J Kawaguchi Masato M Canovatchel William W Meininger Gary G

Diabetes care 20130405 9

<h4>Objective</h4>To evaluate the efficacy and safety of canagliflozin, a sodium glucose cotransporter 2 inhibitor, compared with sitagliptin in subjects with type 2 diabetes inadequately controlled with metformin plus sulfonylurea.<h4>Research design and methods</h4>In this 52-week, randomized, double-blind, active-controlled, phase 3 study, subjects using stable metformin plus sulfonylurea (N = 755) received canagliflozin 300 mg or sitagliptin 100 mg daily. Primary end point was change from ba ...[more]

PMID: 23564919

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Project description:The aim of this work was to evaluate the efficacy and safety of canagliflozin vs placebo and sitagliptin in patients with type 2 diabetes who were being treated with background metformin.This randomised, double-blind, four-arm, parallel-group, Phase 3 study was conducted at 169 centres in 22 countries between April 2010 and August 2012. Participants (N?=?1,284) with type 2 diabetes aged ? 18 and ? 80 years who had inadequate glycaemic control (HbA1c ? 7.0% [53 mmol/mol] and ?10.5% [91 mmol/mol]) on metformin therapy received canagliflozin 100 mg or 300 mg, sitagliptin 100 mg, or placebo (n?=?368, 367, 366, 183, respectively) for a 26 week, placebo- and active-controlled period followed by a 26 week, active-controlled period (placebo group switched to sitagliptin [placebo/sitagliptin]) and were included in the modified intent-to-treat analysis set. Randomisation was performed using a computer-generated schedule; participants, study centres and the sponsor were blinded to group assignment. The primary endpoint was change from baseline in HbA1c at week 26; secondary endpoints included changes in HbA1c (week 52) and fasting plasma glucose (FPG), body weight, and systolic blood pressure (BP; weeks 26 and 52). Adverse events (AEs) were recorded throughout the study.At week 26, canagliflozin 100 mg and 300 mg reduced HbA1c vs placebo (-0.79%, -0.94%, -0.17%, respectively; p?<?0.001). At week 52, canagliflozin 100 mg and 300 mg demonstrated non-inferiority, and canagliflozin 300 mg demonstrated statistical superiority, to sitagliptin in lowering HbA1c (-0.73%, -0.88%,-0.73%, respectively); differences (95% CI) vs sitagliptin were 0% (-0.12, 0.12) and -0.15% (-0.27, -0.03), respectively. Canagliflozin 100 mg and 300 mg reduced body weight vs placebo (week 26: -3.7%, -4.2%, -1.2%, respectively; p?<?0.001) and sitagliptin (week 52: -3.8%, -4.2%, -1.3%, respectively; p?<?0.001). Both canagliflozin doses reduced FPG and systolic BP vs placebo (week 26) and sitagliptin (week 52) (p?<?0.001). Overall AE and AE-related discontinuation rates were generally similar across groups, but higher with canagliflozin 100 mg. Genital mycotic infection and osmotic diuresis-related AE rates were higher with canagliflozin; few led to discontinuations. Hypoglycaemia incidence was higher with canagliflozin.Canagliflozin improved glycaemia and reduced body weight vs placebo (week 26) and sitagliptin (week 52) and was generally well tolerated in patients with type 2 diabetes on metformin.ClinicalTrials.gov NCT01106677 FUNDING: This study was supported by Janssen Research & Development, LLC.

Project description:INTRODUCTION:The aim of this study was to assess the efficacy of co-administering sitagliptin to patients with inadequate glycemic control following treatment with metformin (MET), sulfonylurea (SU), or MET + SU. METHODS:A cohort of 25,386 patients with type 2 diabetes mellitus (hemoglobin A1c [HbA1C] >53 mmol/mol or 7%), newly treated with sitagliptin between 2007 and 2013, was sourced from UK general practices via The Health Improvement Network database. Among these, eligible patients were segregated into three groups: MET (n = 3364), SU (n = 509), or MET + SU therapy (n = 5929). The relative efficacy of sitagliptin added to SU or MET + SU compared with sitagliptin added to MET monotherapy was assessed with regards to HbA1c and body weight changes from baseline up to 52 weeks. The glycemic efficacy was a measure of average treatment effects obtained from multivariable linear regression models and propensity score-matching analysis. RESULTS:A total of 9802 patients were included in the study. Overall, addition of sitagliptin 100 mg once daily resulted in 5.5 mmol/mol (0.5%) HbA1c reduction (P < 0.001) and 0.8 kg weight reduction at 1 year (P < 0.001). Efficacy was similar across the treatment groups, but in patients with baseline HbA1c ≥9% adding sitagliptin to MET + SU produced a significantly smaller reduction in HbA1c when compared to the reference group MET (MET + SU vs. MET only: -0.5% vs. -0.7%, P < 0.001). The mean HbA1c reduction from baseline within this subgroup of patients was not significantly different between SU and MET monotherapies (-0.8% vs. -0.7%, respectively, P = 0.4). Across treatment groups, HbA1c reductions with add-on sitagliptin occurred after 24 weeks of treatment with a peak reduction occurring between 36 and 48 weeks, and receded after week 48. CONCLUSION:In a real-world general practice setting, sitagliptin was effective in patients with suboptimal glycemic control with MET, SU or dual therapy, maximum between 36 and 48 weeks, but in patients with HbA1c of >9% receiving MET + SU therapy, adding sitagliptin, as a third agent, conferred minimal benefit.

Dataset Information

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.

Publications

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.

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