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.

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.