Efficacy and Safety of Once‐Weekly and Once‐Daily Basal Insulins in Type 1 Diabetes Mellitus: A Systematic Review and Network Meta‐Analysis of Clinical Trials

Abstract

Abstract

AIMS: Once-weekly basal insulins, icodec and efsitora alfa, were developed to improve treatment adherence and glycemic control and appear to be as effective as once-daily degludec in reducing HbA1c in type 1 diabetes (T1DM). However, higher rates of clinically significant hypoglycemias were associated with both once-weekly insulins. This network meta-analysis compares the efficacy and safety of once-weekly and once-daily basal insulins in T1DM. METHODS: PubMed and Embase were searched (up to April, 2025) to identify phase 3 clinical trials evaluating basal insulins in T1DM (icodec, efsitora alfa, degludec 100, glargine [100 and 300], detemir, and NPH). Change in HbA1c and weight, risk of hypoglycemias (overall and severe), and serious adverse events (AEs) were assessed at week 26 and 52. RESULTS: Nineteen studies were included. At week 52, icodec reduced HbA1c more than degludec 100 (-0.17% [95% CrI: -0.28; -0.06]), glargine 100 (-0.17% [95% CrI: -0.32; -0.02]), detemir (-0.17% [95% CrI: -0.32; -0.02]), and NPH (-0.59% [95% CrI: -0.85; -0.34]), while efsitora alfa reduced HbA1c more than NPH (-0.45% [95% CrI: -0.70; -0.19]). Icodec showed a higher overall hypoglycemia risk at week 52 compared with degludec 100 (OR 1.64; 95% CrI 1.07-2.54) and detemir (OR 2.08; 95% CrI 1.01-4.39), but no increased risk of severe hypoglycemias or serious AEs. CONCLUSIONS: In T1DM, once-weekly basal insulins appear broadly comparable in reducing HbA1c at week 52. Although icodec showed a higher overall hypoglycemia risk, evidence suggests a comparable risk of severe hypoglycemias between treatments.