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Adverse drug events observed in patients with type 2 diabetes mellitus treated with 100 mg versus 300 mg canagliflozin: a systematic review and meta-analysis of published randomized controlled trials.

ABSTRACT: Nowadays, canagliflozin monotherapy, or in combination with other oral hypoglycemic agents (OHAs), is often administered in patients who are treated for type 2 diabetes mellitus (T2DM). Therefore, we aimed to systematically compare the adverse drugs events (AEs) which were associated with 100 mg versus 300 mg canagliflozin respectively, using a large number of randomized patients with T2DM which were obtained from published trials.Randomized controlled trials (RCTs) comparing 100 mg versus 300 mg canagliflozin in patients who were treated for T2DM were searched from electronic databases. AEs reported during a follow up period ranging from 12 to 104 weeks were considered as the clinical endpoints in this analysis. We calculated odds ratios (OR) with 95% confidence intervals (CIs) and the analyses were carried out by RevMan 5?·?3 software.Ten trials involving a total number of 5394 patients (2604 patients who were treated with 100 mg canagliflozin and 2790 patients who were treated with 300 mg canagliflozin) were included. The current results showed that serious AEs were not significantly higher in patients who were treated by 300 mg canagliflozin, with OR: 1.01, 95% CI: 0.79-1.29; P?=?0.93. Also, a similar rate of death was observed in patients who were treated by either 100 or 300 mg canagliflozin with OR: 1.13, 95% CI: 0.43-2.94; P?=?0.80. Urinary tract infections, postural dizziness and hypoglycemia were also similarly manifested, with OR: 0.93, 95% CI: 0.70-1.23; P?=?0.61, OR: 1.51, 95% CI: 0.42-5.37; P?=?0.53 and OR: 0.96, 95% CI: 0.81-1.13; P?=?0.60 respectively. However, drug discontinuation due to AEs significantly favored 100 mg canagliflozin only during this unequal follow-up period with OR: 1.35, 95% CI: 1.06-1.72; P?=?0.01, but it was not significantly different when trials with similar follow-up periods were analyzed.300 mg canagliflozin was not associated with significantly higher adverse events compared to 100 mg canagliflozin in those patients who were treated for T2DM. However, because this result was partly affected by other anti-diabetic medications which were included in the treatment regimen, further studies based on patients who were treated strictly on canagliflozin monotherapy should be recommended to completely solve this issue.

SUBMITTER: Bundhun PK

PROVIDER: S-EPMC5392384 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

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Adverse drug events observed in patients with type 2 diabetes mellitus treated with 100 mg versus 300 mg canagliflozin: a systematic review and meta-analysis of published randomized controlled trials.

Bundhun Pravesh Kumar PK Janoo Girish G Huang Feng F

BMC pharmacology & toxicology 20170416 1

<h4>Background</h4>Nowadays, canagliflozin monotherapy, or in combination with other oral hypoglycemic agents (OHAs), is often administered in patients who are treated for type 2 diabetes mellitus (T2DM). Therefore, we aimed to systematically compare the adverse drugs events (AEs) which were associated with 100 mg versus 300 mg canagliflozin respectively, using a large number of randomized patients with T2DM which were obtained from published trials.<h4>Methods</h4>Randomized controlled trials ( ...[more]

PMID: 28411624

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Project description:INTRODUCTION:Agents that inhibit sodium glucose co-transporter 2 (SGLT2), including canagliflozin and dapagliflozin, are approved in the United States for the treatment of adults with type 2 diabetes mellitus (T2DM). SGLT2 inhibition lowers blood glucose by increasing urinary glucose excretion, which leads to a mild osmotic diuresis and a net loss of calories that are associated with reductions in body weight and blood pressure. This analysis evaluated the cost-effectiveness of canagliflozin 300 mg versus dapagliflozin 10 mg in patients with T2DM inadequately controlled with metformin in the United States. METHODS:A 30-year cost-effectiveness analysis was performed using the validated Economic and Health Outcomes Model of T2DM (ECHO-T2DM) from the perspective of the third-party health care system in the United States. Patient demographics, biomarker values, and treatment effects for the ECHO-T2DM model were sourced primarily from a network meta-analysis (NMA) that included studies of canagliflozin and dapagliflozin in patients with T2DM on background metformin. Costs were derived from sources specific to the United States. Outcomes and costs were discounted at 3%. Sensitivity analyses that varied key model parameters were conducted. RESULTS:Canagliflozin 300 mg dominated dapagliflozin 10 mg as an add-on to metformin over 30 years, with an estimated cost offset of $13,991 and a quality-adjusted life-year gain of 0.08 versus dapagliflozin 10 mg. Results were driven by the better HbA1c lowering achieved with canagliflozin, which translated to less need for insulin rescue therapy. Findings from sensitivity analyses were consistent with the base case. CONCLUSION:These results suggest that canagliflozin 300 mg is likely to provide better health outcomes at a lower overall cost than dapagliflozin 10 mg in patients with T2DM inadequately controlled with metformin from the perspective of the United States health care system. FUNDING:Janssen Scientific Affairs, LLC and Janssen Global Services, LLC.

Project description:The effects of canagliflozin, a sodium glucose co-transporter 2 inhibitor, on blood pressure (BP) and osmotic diuresis- and intravascular volume reduction-related adverse events (AEs) were evaluated using pooled data from four placebo-controlled, phase 3 studies in patients with type 2 diabetes mellitus (T2DM; N=2313). At baseline, 1332 (57.6%) patients were taking an antihypertensive medication. Canagliflozin 100 mg and 300 mg provided reductions (95% confidence interval [CI]) from baseline in systolic BP (SBP) compared with placebo (-4.3 mm Hg [-5.0 to -3.5], -5.0 mm Hg [-5.8 to -4.2], and -0.3 mm Hg [-1.2 to 0.5], respectively) and in diastolic BP (DBP; -2.5 mm Hg [-2.9 to -2.0], -2.4 mm Hg [-2.9 to -1.9], and -0.6 mm Hg [-1.1 to -0.02], respectively). Placebo-subtracted reductions (95% CI) in SBP with canagliflozin 100 mg and 300 mg were -4.0 mm Hg (-5.1 to -2.8) and -4.7 mm Hg (-5.8 to -3.5) and reductions in DBP were -1.9 mm Hg (-2.6 to -1.2) and -1.9 mm Hg (-2.6 to -1.1), respectively. Compared with the overall population, patients with elevated baseline SBP (≥140 mm Hg) had numerically greater absolute SBP reductions (95% CI) with canagliflozin 100 mg and 300 mg and placebo (-12.8 mm Hg [-15.2 to -10.5], -14.2 mm Hg [-16.4 to -12.0], and -6.8 mm Hg [-9.1 to -4.5], respectively). Numerically greater DBP reductions were seen in patients with DBP ≥90 mm Hg at baseline (-5.9 mm Hg [-8.2 to -3.6], -9.0 mm Hg [-11.1 to -6.9], and -7.4 mm Hg [-9.6 to -5.1], respectively). In patients with elevated SBP at baseline, placebo-subtracted reductions (95% CI) in SBP with canagliflozin 100 mg and 300 mg were -6.0 mm Hg (-9.1 to -2.9) and -7.4 mm Hg (-10.4 to -4.4), respectively. Placebo-subtracted changes in DBP were 1.5 mm Hg (-1.6 to 4.5) and -1.6 mm Hg (-4.5 to 1.2), respectively, in those with elevated DBP at baseline. Canagliflozin 100 mg and 300 mg were associated with increased incidence of osmotic diuresis-related AEs (e.g., pollakiuria [increased urine volume] and polyuria [increased urine frequency]) vs placebo (6.7%, 5.6%, and 0.8%). The incidence of intravascular volume reduction-related AEs (eg, orthostatic hypotension and postural dizziness) was low across groups (1.2%, 1.3%, and 1.1%). In summary, canagliflozin was associated with reduced BP in patients with T2DM across a range of baseline BPs, with increased incidence of AEs related to osmotic diuresis but not intravascular volume reduction.

Dataset Information

Adverse drug events observed in patients with type 2 diabetes mellitus treated with 100 mg versus 300 mg canagliflozin: a systematic review and meta-analysis of published randomized controlled trials.

Publications

Adverse drug events observed in patients with type 2 diabetes mellitus treated with 100 mg versus 300 mg canagliflozin: a systematic review and meta-analysis of published randomized controlled trials.

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