Jacqueline Yee

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

OBJECTIVE 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. RESEARCH DESIGN AND METHODS 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. RESULTS 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. CONCLUSIONS 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.

Efficacy and safety of canagliflozin over 52 weeks in patients with type 2 diabetes on background metformin and pioglitazone

The efficacy and safety of canagliflozin, a sodium glucose co‐transporter 2 inhibitor, was evaluated in patients with type 2 diabetes mellitus (T2DM) inadequately controlled with metformin and pioglitazone.

Efficacy and safety of canagliflozin by baseline HbA1c and known duration of type 2 diabetes mellitus.

AIMS Canagliflozin, a sodium glucose co-transporter 2 inhibitor, has demonstrated glycemic improvements across studies of patients with type 2 diabetes mellitus (T2DM). The impact of canagliflozin on HbA1c lowering was assessed by baseline HbA1c and known duration of T2DM. METHODS This post hoc analysis pooled data from patients with T2DM enrolled in four 26-week, placebo-controlled, Phase 3 studies of canagliflozin (N=2313). Change in HbA1c from baseline to Week 26 was assessed in the overall population and in subgroups by baseline HbA1c (<8.0%, 8.0%-<9.0%, and ≥9.0%) and known duration of T2DM (<5 years, 5-<10 years, and ≥10 years). RESULTS Relative to placebo, canagliflozin 100 and 300 mg provided greater HbA1c reductions in the overall population. Progressively larger placebo-subtracted reductions in HbA1c with canagliflozin 100 and 300 mg were seen with increasing baseline HbA1c. HbA1c reductions were similar across subgroups based on known duration of T2DM. Both canagliflozin doses were generally well tolerated across subgroups, with a safety and tolerability profile consistent with that seen in Phase 3 studies. CONCLUSIONS Canagliflozin provided glycemic improvements in patients with T2DM across a range of baseline HbA1c and known duration of T2DM.

Achievement of treatment goals with canagliflozin in patients with type 2 diabetes mellitus: a pooled analysis of randomized controlled trials.

Abstract Objective: To evaluate attainment of diabetes-related treatment goals with canagliflozin, a sodium glucose co-transporter 2 inhibitor, versus placebo in patients with type 2 diabetes mellitus (T2DM). Research design and methods: Data were pooled from four 26-week, placebo-controlled, Phase 3 studies of patients with T2DM (N = 2313). Goal attainment with canagliflozin 100 and 300 mg versus placebo was evaluated in the overall population, and in subgroups based on age and sex, at baseline and Week 26. Clinical trial registration: ClinicalTrials.gov NCT01081834, NCT01106677, NCT01106625, NCT01106690. Main outcome measures: Proportion of patients achieving hemoglobin A1C (A1C) <7.0% and ≤6.5%, systolic blood pressure (SBP) <140 and <130 mmHg, diastolic blood pressure (DBP) <90 and <80 mmHg, low-density lipoprotein cholesterol (LDL-C) <100 mg/dL (2.6 mmol/L), high-density lipoprotein cholesterol (HDL-C) ≥40 mg/dL (1.0 mmol/L), and the composite endpoint of A1C <7.0%, BP <130/80 mmHg, and LDL-C <100 mg/dL (2.6 mmol/L) at baseline and Week 26, and proportion with body weight reduction ≥5% at Week 26. Results: At baseline, similar proportions of patients met diabetes-related treatment goals across groups. At Week 26, a greater proportion of patients achieved A1C, SBP, DBP, and HDL-C goals with canagliflozin 100 and 300 mg compared with placebo. More patients achieved body weight reduction of ≥5% with canagliflozin 100 and 300 mg versus placebo at Week 26. Fewer patients had LDL-C <100 mg/dL (2.6 mmol/L) at Week 26 with canagliflozin 100 and 300 mg versus placebo. Canagliflozin 100 and 300 mg also provided better attainment of the composite endpoint of A1C <7.0%, BP <130/80 mmHg, and LDL-C <100 mg/dL (2.6 mmol/L) compared with placebo. Attainment of diabetes-related treatment goals was generally similar regardless of age and sex. Key limitations of this analysis include the selection of specific treatment targets that may not be reflective of all patient experiences, the non-prespecified, post hoc nature of the analysis, and the short duration of studies included in the pooled population. Conclusion: Canagliflozin was associated with better attainment of diabetes-related treatment goals compared with placebo, and was generally well tolerated at 26 weeks.