A Systematic Review and Network Meta-Analysis Assessing the Effectiveness and Tolerability of Gliptins and Sulfonylureas as Monotherapy in Patients with Type 2 Diabetes Mellitus If Metformin is not Considered Appropriate

Abstract

A significant proportion of patients with type-2-diabetes mellitus (T2DM) are unable to take Metformin as recommended first-line therapy due to gastrointestinal intolerance or contraindications such as chronic kidney disease. In contrast to combination therapy no network meta-analysis (NMA) has been undertaken for oral anti-diabetic drugs (OAD) as monotherapy in this population - particularly with respect to gliptins and sulfonylureas as second-line options. The purpose of this study is to assess the comparative effectiveness and tolerability of gliptins versus sulfonylureas in terms of glycated hemoglobin (HbA1c), body weight and hypoglycemia. A systematic review was conducted searching bibliographic databases, reports of regulatory authorities and clinical trial registries through July 2012 to identify randomized controlled trials in adult T2DM patients receiving at least 12 weeks of OAD monotherapy or placebo. A Bayesian NMA was performed to yield mixed treatment comparisons. Consistency was examined by the node split method. A total of 62 studies enrolling 21,302 patients informed the entire network. Due to their improved model fit estimates from random effect models are reported to account for heterogeneity across the set of studies. After a mean follow-up of 32 weeks, the difference in mean HbA1c was 0.26,0. 95 credible interval (CrI0.95): [0.1; 0.42], in favour of sulfonylureas. However, gliptins induced weight loss (difference in means: -1.21 kg; CrI0.95: [-1.57; -0.84] ) and were associated with a considerably lower incidence of any hypoglycemia compared to sulfonylureas (odds ratio: 0.22; CrI0.95: [0.15; 0.31] ). All effect estimates were statistically significant and consistent in terms of combining direct and indirect evidence. This is the first network assessing OAD monotherapy that can readily be extended to emerging therapies. With regard to glycemic control gliptins were slightly inferior to sulfonylureas, whereas they positively affected body weight and risk of hypoglycemia, confirming their role in second-line monotherapy.