Efficacy and safety of premixed versus basal-bolus regimens as intensification of insulin therapy in patients with type 2 diabetes mellitus: A systematic review and meta-analysis of randomized clinical trials

Abstract

Aim

To estimate the efficacy and safety of the basal-bolus and premixed insulin as intensification regimens in patients with type 2 diabetes mellitus (T2DM).

Methods

A comprehensive search of online databases was performed until December 2022 to identify randomized controlled trials (RCTs) comparing premixed insulin versus basal-bolus regimen with treat-to-target intention. The Cochrane ROB-2 tool and GRADE approach were used for quality assessment and certainty of the evidence, respectively. Pooled weighted mean difference (WMD) and odds ratio (OR) were calculated using random-effects meta-analysis models.

Results

Eighteen RCTs were included in the meta-analysis, and 66% had a low risk of bias. We found no significant difference between the two regimens regarding HbA1c reduction (WMD: 0.03% [−0.05%, 0.10%]). The basal-bolus regimen improved fasting plasma glucose (FPG) more than the premixed regimen (WMD: 6.35 mg/dL [0.31, 12.39]). Both had similar effects on weight gain. The odds of developing overall, nocturnal, and severe hypoglycemia were comparable (pooled OR: 0.9, 1.02, and 1.00, respectively) with no heterogeneity. Findings of the model were robust. The certainty of the evidence was moderate to high for all outcomes except FPG.

Conclusions

Two regimens are clinically comparable. Patient preference should be considered when adopting an individualized approach in a real-world setting.