Abstract
IntroductionAlogliptin 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.MethodsA 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.ResultsThe 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.ConclusionThis 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).Electronic supplementary materialThe online version of this article (doi:10.1007/s13300-017-0245-8) contains supplementary material, which is available to authorized users.
Highlights
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)
In addition to these six studies, an abstract in support of the efficacy and safety of alogliptin evaluating subjects treated with only metformin and SU at baseline from the EXAMINE trial [10] was provided by Takeda, along with a non-indexed study identified from ClinicalTrials.gov (Identifier: NCT01590771) [33], taking the total amount of studies to eight
Using data from the EXAMINE subgroup, the current study reported in this paper presents the methods and results of a decision-focused systemic literature review (SLR) and network meta-analysis (NMA) to investigate the relative efficacy and safety of alogliptin 25 mg in triple therapy compared with the other DPP-4 inhibitors currently used in UK clinical practice
Summary
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). Combination therapy with a dipeptidyl peptidase-4 (DPP-4) inhibitor and metformin or sulfonylurea (i.e., dual therapy) results in substantial and additive glucose-lowering effects in patients with T2DM. The safety and efficacy of alogliptin as monotherapy and combination therapy in patients with T2DM have been evaluated in numerous clinical trials [1]. Pratley et al [3] evaluated combination therapy of alogliptin added to glyburide (a sulfonylurea, SU) in 500 patients with T2DM inadequate controlled on SU monotherapy and showed significant HbA1c reductions of alogliptin 25 mg (-0.53%) compared with placebo (?0.01%; P\0.001). More patients in the alogliptin 25 mg group achieved HbA1c reductions [0.5% (26.3% with placebo and 50.5% with 25 mg of alogliptin; P\0.001)
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