Basal Insulin Regimens for Adults with Type 1 Diabetes Mellitus: A Systematic Review and Network Meta-Analysis

Objective: To assess the relative efficacy and safety of basal insulin regimens in adults with type 1 diabetes mellitus (T1DM). Methods: A systematic review and Bayesian network meta-analysis (NMA) of randomized controlled trials comparing two or more basal insulin regimens were conducted. The following basal insulin regimens were included: Neutral Protamine Hagedorn (iNPH) (once [od], twice [bid], and four times daily [qid]), insulin detemir (iDet) (od and bid), insulin glargine 100 IU (iGlarg) (od), and insulin degludec (iDegl) (od). We searched the following databases: MEDLINE via OVID, Embase via OVID, and the Cochrane Library (Wiley). Study quality was appraised using Cochrane risk-of-bias checklist for randomized controlled trials. Two outcomes (change in hemoglobin A_1c [HbA_1c] and rate of severe/major hypoglycemia [SH]) were analyzed. Network inconsistency was assessed using Bucher and chi-square tests. Results: Thirty studies met the eligibility criteria. Twenty-five were included in the HbA_1c network and 16 in the SH network. All studies were of moderate quality. No network inconsistency was evident in the HbA_1c network. Of the seven regimens of interest, iDet (bid) had the highest probability of being best (mean change in HbA_1c −0.48; 95% credible interval −0.69 to −0.29). In contrast, the SH network demonstrated both considerable uncertainty and significant network inconsistency (χ² test, P = 0.003). Conclusions: Of the specified frequency regimens, iDet (bid) had the highest probability of being the best basal insulin regimen in terms of reduction in HbA_1c. Ranking of the regimens in terms of the SH rate was highly uncertain and no clear conclusion could be made.