Dataset Information

Efficacy and safety of canagliflozin in patients with type 2 diabetes based on history of cardiovascular disease or cardiovascular risk factors: a post hoc analysis of pooled data.

ABSTRACT:

Background

Treatment of patients with type 2 diabetes mellitus (T2DM) and a history of cardiovascular (CV) disease or CV risk factors may present clinical challenges due to the presence of comorbid conditions and the use of concomitant medications. The sodium glucose co-transporter 2 inhibitor, canagliflozin, has been shown to improve glycaemic control and reduce body weight and blood pressure (BP) with a favourable tolerability profile in a broad range of patients with T2DM. This post hoc analysis assessed the efficacy and safety of canagliflozin in patients with T2DM based on CV disease history or CV risk factors.

Methods

Analyses were based on pooled data from four 26-week, placebo-controlled, Phase 3 studies that evaluated canagliflozin 100 and 300 mg in patients with T2DM (N = 2313; mean HbA1c, 8.0%; body weight, 89 kg; systolic BP, 128 mmHg). Changes from baseline to week 26 in HbA1c, body weight, and systolic BP were assessed based on history of CV disease, history of hypertension, baseline statin use, and number of CV risk factors. Safety was assessed based on adverse event (AE) reports.

Results

At week 26, both canagliflozin doses lowered HbA1c, body weight, and systolic BP compared with placebo in patients with and without CV disease history or risk factors. Placebo-subtracted HbA1c reductions with canagliflozin 100 and 300 mg were similar in patients with a history of CV disease (-0.95 and -1.07%) versus no history of CV disease (-0.71 and -0.90%), history of hypertension (-0.72 and -0.89%) versus no history of hypertension (-0.73 and -0.95%), baseline statin use (-0.77 and -0.99%) versus no statin use (-0.69 and -0.85%), and 0-1 CV risk factor (-0.72 and -0.87%) versus ≥2 CV risk factors (-0.74 and -1.02%). Similar body weight and systolic BP reductions were seen with canagliflozin versus placebo across subgroups. The incidence of AEs, AEs leading to discontinuation, and serious AEs was similar across subgroups.

Conclusions

The efficacy and safety of canagliflozin were generally consistent across subgroups of patients with T2DM and varying degrees of CV disease history or risk factors. Trial registration numbers and dates ClinicalTrials.gov: NCT01081834, 4 March 2010; NCT01106625, 1 April 2010; NCT01106677, 1 April 2010; NCT01106690, 1 April 2010.

SUBMITTER: Davies MJ

PROVIDER: S-EPMC5361783 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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Efficacy and safety of canagliflozin in patients with type 2 diabetes based on history of cardiovascular disease or cardiovascular risk factors: a post hoc analysis of pooled data.

Davies Michael J MJ Merton Katherine K Vijapurkar Ujjwala U Yee Jacqueline J Qiu Rong R

Cardiovascular diabetology 20170321 1

<h4>Background</h4>Treatment of patients with type 2 diabetes mellitus (T2DM) and a history of cardiovascular (CV) disease or CV risk factors may present clinical challenges due to the presence of comorbid conditions and the use of concomitant medications. The sodium glucose co-transporter 2 inhibitor, canagliflozin, has been shown to improve glycaemic control and reduce body weight and blood pressure (BP) with a favourable tolerability profile in a broad range of patients with T2DM. This post h ...[more]

PMID: 28327140

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Project description:To compare the efficacy and safety of canagliflozin, a sodium glucose co-transporter 2 inhibitor developed to treat type 2 diabetes mellitus (T2DM), in individuals younger than 75 and those aged 75 and older.Randomized Phase 3 studies.International study centers.Adults with T2DM.Changes from baseline in glycosylated hemoglobin (HbA1c ), fasting plasma glucose (FPG), blood pressure (BP), and body weight were measured. Efficacy was evaluated using pooled data from six randomized, double-blind, placebo-controlled studies (N = 4,158; n = 3,975 aged <75, n = 183 aged ≥75). Safety was assessed based on adverse event (AE) reports from eight randomized, double-blind, placebo- and active-controlled studies (N = 9,439; n = 8,949 aged <75, n = 490 aged ≥75).Canagliflozin 100 and 300 mg were associated with placebo-subtracted mean reductions in HbA1c in participants younger than 75 (-0.69% and -0.85%, respectively) and aged 75 and older (-0.65% and -0.55%, respectively). Dose-related reductions in FPG, body weight, and BP were seen with canagliflozin 100 and 300 mg in participants in both age groups. Overall AE incidence was 67.1% with canagliflozin 100 mg, 68.6% with canagliflozin 300 mg, and 65.9% with non-canagliflozin (pooled group of comparators in all studies) in participants younger than 75, and 72.4%, 79.1%, and 72.3%, respectively, in those aged 75 and older, with a similar safety profile in both groups. The incidence of volume depletion-related AEs was 2.2%, 3.1%, and 1.4% in participants younger than 75 with canagliflozin 100 and 300 mg and non-canagliflozin, respectively, and 4.9%, 8.7%, and 2.6%, respectively, in those aged 75 and older.Canagliflozin improved glycemic control, body weight, and BP in participants aged 75 and older. The overall incidence of AEs was high across treatment groups in participants aged 75 and older and higher than in those younger than 75. The safety profile of canagliflozin was generally similar in both age groups, with a higher incidence of AEs related to volume depletion observed with canagliflozin in participants aged 75 and older than in those younger than 75. These findings support canagliflozin, starting with the 100-mg dose, as an effective therapeutic option for older adults with T2DM.

Project description:BackgroundThe randomized, double-blind CANTATA-SU (CANagliflozin Treatment And Trial Analysis Sulfonyl Urea) clinical trial compared the use of canagliflozin (100 mg or 300 mg) and maximally tolerated glimepiride (6-8 mg) over 104 weeks as add-on therapy for patients with type 2 diabetes mellitus (T2DM) inadequately controlled with metformin. Compared with glimepiride, canagliflozin use was associated with durable reductions in glycated hemoglobin (A1C), blood pressure (BP), and body weight. The aim of this post-hoc analysis of the CANTATA-SU trial was to assess the comparative efficacy of canagliflozin and glimepiride in the attainment of recently updated diabetes-related quality measures (QMs) for up to 104 weeks of treatment.MethodsThis post-hoc analysis evaluated the proportions of patients achieving individual diabetes-related QMs using data from the randomized, double-blind, Phase 3 CANTATA-SU trial. Change in A1C from baseline, and proportions of the study population achieving QMs: A1C <7.0 %, <8.0 %, and >9.0 % were assessed. Secondary endpoints included change in BP from baseline, and the proportions of the study population achieving QMs related to BP and body weight.ResultsThe proportions of patients in the canagliflozin 100 mg, canagliflozin 300 mg, and glimepiride groups meeting criteria for all QMs were similar at baseline. At 52 and 104 weeks of treatment, canagliflozin 100 mg and canagliflozin 300 mg provided better or similar reductions in A1C from baseline and achievement of glycemic control QMs compared with glimepiride. At 52 and 104 weeks of treatment, the attainment of QMs related to reductions in body weight and BP all favored canagliflozin compared with glimepiride. Canagliflozin was associated with lower incidence of documented hypoglycemia and severe hypoglycemia compared with glimepiride.ConclusionsUsing the recently adjusted and currently accepted diabetes-related QMs, this analysis observed superior glycemic control with canagliflozin compared with maximally tolerated glimepiride in patients with T2DM who were previously poorly controlled on metformin monotherapy. Compared with maximally tolerated glimepiride, canagliflozin resulted in better achievement of diabetes-related QMs related to weight loss and BP, and was associated with lower incidences of hypoglycemic events.Trial registrationClinical trial registry name: CANagliflozin Treatment And Trial Analysis-Sulfonylurea (CANTATA-SU) SGLT2 Add-on to Metformin Versus Glimepiride.Clinical trial registration numberNCT00968812 , registered August 28, 2009.

Project description:IntroductionThe ADA-EASD consensus report recommends using glucagon-like peptide-1 receptor agonists (GLP-1RAs) as the first injectable therapy prior to basal insulin in most patients with type 2 diabetes (T2D) not at glycemic goals after oral anti-hyperglycemia medications (OH). The objective of this analysis was to assess the glycemic efficacy of once-weekly dulaglutide 1.5 mg in patients with T2D when added on a background of commonly used OH regimens.MethodsPatients from seven phase 3 AWARD [Assessment of Weekly AdministRation of LY2189265 (Dulaglutide) in Diabetes] trials, where once-weekly dulaglutide 1.5 mg was added to OHs, were pooled into the following categories based on OH regimens: metformin (MET), sulfonylurea (SU), MET + SU, MET + pioglitazone, and MET + SGLT2i. Change from baseline in glycated hemoglobin A1c (HbA1c), fasting serum glucose and body weight, proportion of patients reaching target HbA1c < 7%, and safety parameters were assessed.ResultsA total of 1784 patients treated with once-weekly dulaglutide 1.5 mg were included in this analysis. Baseline characteristics of the overall population were (mean ± standard deviation): age, 55.4 ± 9.8 years, HbA1c: 8.2 ± 1.0%, body mass index: 31.4 ± 5.4 kg/m2, duration of diabetes: 8.0 ± 5.6 years, and 878 (49.2%) were female. At 6 months, the addition of once-weekly dulaglutide 1.5 mg to various OH regimens significantly reduced HbA1c (- 1.3 to - 1.6%) and fasting blood glucose (- 29 to - 45 mg/dl) from baseline in all groups (p < 0.001), with 39-61% and 52-76% of these patients achieving HbA1c targets of ≤ 6.5% and < 7%, respectively. Significant reductions in body weight (- 0.8 to - 2.9 kg) were also observed in all groups (p < 0.001). Nausea, vomiting, and diarrhea were reported by 10-35%, 4-19%, and 6-28% of patients, respectively. Severe hypoglycemia occurred in one patient (MET + SU).ConclusionThe addition of a once-weekly GLP-1RA, dulaglutide, demonstrated clinically meaningful HbA1c reduction in patients with T2D on different background OH regimens, making it an effective first injectable option.FundingEli Lilly and Company.

Project description:BackgroundCanagliflozin is a sodium glucose co-transporter 2 inhibitor developed for the treatment of patients with type 2 diabetes mellitus (T2DM). The efficacy and safety of canagliflozin were evaluated in patients with T2DM <65 and ≥65 years of age.MethodsPooled data from 4 randomised, placebo-controlled, 26-week, Phase 3 studies (N = 2,313) evaluating canagliflozin 100 and 300 mg were analysed by age: <65 years (n = 1,868; mean age, 52.8 years) or ≥65 years (n = 445; mean age, 69.3 years). Efficacy evaluations included change from baseline in glycaemic parameters and systolic blood pressure (BP), and percent change from baseline in body weight. Assessment of safety/tolerability included adverse event (AE) reports, incidence of documented hypoglycaemia, and percent change from baseline in fasting plasma lipids.ResultsCanagliflozin 100 and 300 mg reduced HbA1c and fasting plasma glucose relative to placebo in patients <65 and ≥65 years of age. Both canagliflozin doses reduced body weight and systolic BP relative to placebo in patients <65 and ≥65 years of age. Incidence of overall AEs was similar across all treatment groups in patients <65 and ≥65 years of age. Incidences of serious AEs and AE-related discontinuations were similar across all treatment groups in patients <65 years of age and higher with canagliflozin 100 mg than other groups in patients ≥65 years of age. As in patients <65 years of age, incidences of genital mycotic infections and osmotic diuresis-related AEs were higher with canagliflozin relative to placebo in those ≥65 years of age. Incidences of urinary tract infections (UTIs), renal-related AEs, AEs related to volume depletion, and documented hypoglycaemia episodes were similar across all treatment groups in patients ≥65 years of age; no notable trends were observed with canagliflozin 100 and 300 mg relative to placebo in these AEs among patients <65 years of age. Changes in lipid parameters with canagliflozin were similar in both age subsets.ConclusionsCanagliflozin improved glycaemic control, body weight, and systolic BP, and was generally well tolerated in older patients with T2DM.Trial registrationClinicalTrials.gov, NCT01081834; NCT01106677; NCT01106625; NCT01106690.

Project description:IntroductionRacial disparities in disease activity, clinical outcomes, and treatment survival persist despite advancements in rheumatoid arthritis (RA) therapies and clinical management. In this post hoc analysis of pooled data from the tofacitinib global clinical program, we evaluated the impact of race on the efficacy and safety of tofacitinib in patients with RA.MethodsData were pooled from 15 phase 2-3b/4 studies of patients with RA treated with tofacitinib 5 or 10 mg twice daily, adalimumab, or placebo. Outcomes were stratified by self-reported patient race (White/Black/Asian/Other). Efficacy outcomes to month 12 included: American College of Rheumatology (ACR)20/50/70 responses, Clinical Disease Activity Index (CDAI)/Disease Activity Score in 28 joints, erythrocyte sedimentation rate [DAS28-4(ESR)] low disease activity (LDA) rates, least squares (LS) mean change from baseline (∆) in CDAI, DAS28-4 (ESR), Health Assessment Questionnaire-Disability Index (HAQ-DI), and Pain [Visual Analog Scale (VAS)]. Odds ratios (ORs; 95% CI) versus placebo, and placebo-adjusted ∆LS means were calculated for active treatments using logistic regression model and mixed-effect model of repeated measurements, respectively. Safety outcomes were assessed throughout.ResultsA total of 6355 patients were included (White, 4145; Black, 213; Asian, 1348; Other, 649). For tofacitinib-treated patients, ORs for ACR20/50/70 responses and CDAI/DAS28-4(ESR) LDA rates through month 3 were generally numerically higher for White/Asian/Other versus Black patients. Across active treatments, trends toward higher placebo-adjusted improvements from baseline in CDAI, DAS28-4 (ESR), HAQ-DI, and Pain (VAS) were observed in Asian/Other versus White/Black patients. Numerically higher placebo responses in Black versus White/Asian/Other patients were generally observed across outcomes through month 12. Safety outcomes were mostly similar across treatment/racial groups.ConclusionsIn patients with RA, tofacitinib was efficacious across racial groups with similar safety outcomes; observed racial differences potentially reflect patient demographics or regional practice disparities.Trial registration numbersClinicalTrials.gov identifiers: NCT00147498; NCT00413660; NCT00550446; NCT00603512; NCT00687193; NCT01164579; NCT00976599; NCT01359150; NCT00960440; NCT00847613; NCT00814307; NCT00856544; NCT00853385; NCT01039688; NCT02187055.

Dataset Information

Efficacy and safety of canagliflozin in patients with type 2 diabetes based on history of cardiovascular disease or cardiovascular risk factors: a post hoc analysis of pooled data.

Background

Methods

Results

Conclusions

Publications

Efficacy and safety of canagliflozin in patients with type 2 diabetes based on history of cardiovascular disease or cardiovascular risk factors: a post hoc analysis of pooled data.

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