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

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.

Comparison of antidiabetic drugs added to sulfonylurea monotherapy in patients with type 2 diabetes mellitus: A network meta-analysis

“…Notably, SGLT-2i yielded significant improvements in this parameter when compared with all other agents except GLP-1RA and AGI and was therefore ranked the best. A previous NMA by Kay et al [ 57 ] demonstrated that all DPP-4is were associated with mean body weight gains relative to placebo when added to metformin and SU. Although that study focused on triple combination therapy (DPP-4i + Met + SU), these findings were consistent with our study results.…”

Benefit-Risk Assessment of Alogliptin for the Treatment of Type 2 Diabetes Mellitus

“…These findings are further supported by a meta-analysis examining the efficacy and safety of alogliptin as monotherapy or combination therapy [78, 79]. Here, the number of patients who discontinued due to AEs was not significantly different in patients treated with alogliptin versus placebo or other antidiabetic control treatments (odds ratio [OR] 0.83; 95% confidence interval [CI] 0.61–1.58 for alogliptin 12.5 mg; OR 0.98; 95% CI 0.44–1.58 for alogliptin 25 mg) [78].…”

Efficacy and Safety of Alogliptin in Elderly Patients With Type 2 Diabetes Mellitus

“…Meta-analyses have not found any significant difference in hypoglycemic action among different DPP-4 inhibitors [36, 37]. In a meta-analysis focusing on alogliptin, Kay et al compared the effects of alogliptin with those of four other DPP-4 inhibitors (linagliptin, saxagliptin, sitagliptin, and vildagliptin) in patients with insufficient blood glucose control by treatment with metformin and sulfonylurea (SU), reporting that alogliptin did not differ from the other DPP-4 inhibitors in terms of efficacy and safety [38]. The excretory pathway differs among DPP-4 inhibitors.…”