Dataset Information

Comparative Effectiveness of Adding Alogliptin to Metformin Plus Sulfonylurea with Other DPP-4 Inhibitors in Type 2 Diabetes: A Systematic Review and Network Meta-Analysis.

ABSTRACT:

Introduction

Alogliptin is an oral antihyperglycemic agent that is a selective inhibitor of the enzyme dipeptidyl peptidase-4 (DPP-4), approved for the treatment of type 2 diabetes mellitus (T2DM). There currently exists no comparative data to support the use of alogliptin in combination with metformin (met) and sulfonylurea (SU). A decision-focused network meta-analysis (NMA) was performed to compare the relative efficacy and safety of alogliptin 25 mg once daily to other DPP-4 inhibitors as part of a triple therapy regimen for patients inadequately controlled on metformin and SU dual therapy.

Methods

A systematic literature review was conducted to identify published papers of randomized controlled trials (RCTs) that compared alogliptin with other DPP-4 inhibitors (linagliptin, saxagliptin, sitagliptin, and vildagliptin) at their Summary of Product Characteristics (SmPC) recommended daily doses, added on to metformin and SU. Comprehensive comparative analysis involving frequentist meta-analysis and Bayesian NMA compared alogliptin to each DPP-4 inhibitor separately and collectively as a group. Quasi-random effect models were introduced when random effect models could not be estimated.

Results

The review identified 2186 articles, and 94 full-text articles were assessed for eligibility. Eight RCTs contained appropriate data for inclusion in the NMA. All analyses over all trial population sets produced very similar results, and show that alogliptin 25 mg is as least as effective (as measured by change in HbA1c from baseline, but supported by other outcome measures: change in body weight and FPG from baseline) and safe (as measured by incidence of hypoglycemia and adverse events leading to study discontinuation) as all the other DPP-4 inhibitors in triple therapy.

Conclusion

This decision-focused systematic review and NMA demonstrated alogliptin 25 mg daily to have similar efficacy and safety compared to other DPP-4 inhibitors, for the treatment of T2DM in adults inadequately controlled on metformin and SU. (Funded by Takeda Development Centre Americas; EXAMINE ClinicalTrials.gov number, NCT00968708).

SUBMITTER: Kay S

PROVIDER: S-EPMC5380505 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:IntroductionENDURE (ClinicalTrials.gov identifier, NCT00856284), a multicenter, double-blind, active-controlled study of 2639 patients with uncontrolled type 2 diabetes mellitus (T2DM), found that metformin in combination with alogliptin (12.5 and 25 mg doses), when compared to standard add-on therapy (sulfonylurea, SU), exerted sustained antihyperglycemic effects over 2 years. This economic analysis of ENDURE aimed to quantify the relationship between increased glycemic durability and cost-effectiveness of alogliptin in the UK clinical setting, and communicate its sustained glycemic benefit in economic terms.MethodsUsing baseline characteristics and treatment effects from the ENDURE trial population, between-group cost-effectiveness analyses compared the combined use of metformin and alogliptin (MET + ALO12.5/25) in patients with inadequately controlled T2DM, as an alternative to metformin and SU (MET + SU). In scenario analyses, an intragroup cost-effectiveness analysis compared MET + ALO12.5/25 with MET + SU; a between-group cost-effectiveness analysis also compared MET + ALO12.5/25 versus MET + SU within a subpopulation of patients who achieved HbA1c control (<7.5%) at 2 years on study drug.ResultsCompared with baseline profiles of patients, combination therapies with alogliptin or SU were associated with improvements in length and quality of life and were cost-effective at established norms. Despite increased drug acquisition costs, alogliptin at 12.5 mg and 25 mg doses resulted in greater predicted lifetime quality-adjusted life year (QALY) gains with associated incremental cost-effectiveness ratios (ICERs) of £10,959/QALY and £7217/QALY compared to SU, respectively.ConclusionThe ENDURE trial and the present cost-effectiveness analysis found that the glycemic durability of alogliptin therapy was associated with improved long-term patient outcomes, QALY gains, and ICERs that were cost-effective when evaluated against standard threshold values. Alogliptin therefore represents a cost-effective treatment alternative to SU as add-on therapy to metformin in patients with poorly managed T2DM.FundingTakeda Development Centre Europe Ltd.

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.