Glycemic Control During Continuous Subcutaneous Insulin Infusion Versus Multiple Daily Insulin Injections in Type 2 Diabetes: Individual Patient Data Meta-analysis and Meta-regression of Randomized Controlled Trials

Abstract

Objective: To compare glycemic control during continuous subcutaneous insulin infusion (CSII) and multiple daily insulin injections (MDI) in people with type 2 diabetes to identify patient characteristics that determine those best treated by CSII.

Research design and methods: Randomized controlled trials were selected comparing HbA_1c during CSII versus MDI in people with type 2 diabetes. Data sources included Cochrane database and Ovid Medline. We explored patient-level determinants of final HbA_1c level and insulin dose using Bayesian meta-regression models of individual patient data and summary effects using two-step meta-analysis. Hypoglycemia data were unavailable.

Results: Five trials were identified, with 287 patients randomized to receive MDI and 303 to receive CSII. Baseline HbA_1c was the best determinant of final HbA_1c: HbA_1c difference (%) = 1.575 - (0.216 [95% credible interval 0.371-0.043] × baseline HbA_1c) for all trials, but with largest effect in the trial with prerandomization optimization of control. Baseline insulin dose was best predictor of final insulin dose: insulin dose difference (units/kg) = 0.1245 - (0.382 [0.510-0.254] × baseline insulin dose). Overall HbA_1c difference was -0.40% (-0.86 to 0.05 [-4.4 mmol/mol (-9.4 to 0.6)]). Overall insulin dose was reduced by -0.25 units/kg (-0.31 to -0.19) (26% reduction on CSII), and by -24.0 units/day (-30.6 to -17.5). Mean weight did not differ between treatments (0.08 kg [-0.33 to 0.48]).

Conclusions: CSII achieves better glycemic control than MDI in people with poorly controlled type 2 diabetes, with ∼26% reduction in insulin requirements and no weight change. The best effect is in those worst controlled and with the highest insulin dose at baseline.

Trial registration: ClinicalTrials.gov NCT02910141.