Efficacy and safety of insulin icodec compared with insulin efsitora in patients with type 2 diabetes: a systematic review and network meta-analysis.

Authors

Jingxin Li, Junxia Wen, Hao Zheng, Cuilu Quan, Jiajie Bi, Yajing Yang, Jing Zhang, Yanhong Shen

Published in

Frontiers in endocrinology. Volume 17. Pages 1902260. Epub Aug 14, 2026.

Abstract

We conducted this network meta-analysis to compare the efficacy and safety of insulin icodec vs insulin efsitora for patients with type 2 diabetes (T2D).
We conducted a comprehensive systematic search across PubMed, the Cochrane Library, and Embase up to November 11, 2025. Eligible trials compared insulin icodec and insulin efsitora against each other, placebo or other glucose-lowering drugs. Primary outcome was change in HbA1c. Secondary outcomes were change in body weight, percentage of patients achieving HbA1c < 7%, change in fasting plasma glucose (FPG), and safety outcomes including level 1 hypoglycemia, level 2 or level 3 hypoglycemia, adverse events (AEs), and serious adverse events (SAEs). We used version 2 of the Cochrane risk-of-bias tool to assess the risk of bias. A frequentist network meta-analysis was used to calculate the risk ratios or mean difference with corresponding 95% confidence intervals.
Thirteen RCTs involving 7,402 participants were included. Insulin icodec resulted in a lower HbA1c level compared to insulin efsitora, but was associated with a higher incidence of level 1 hypoglycemia. The two treatments showed no significant differences in other outcomes, including change in body weight, percentage of patients achieving HbA1c <7%, change in FPG, incidence of level 2 or 3 hypoglycemia, AEs, and SAEs. Compared to daily insulins, insulin icodec led to lower HbA1c levels. Weight gain was lower with insulin glargine than with insulin icodec. A higher percentage of patients in the icodec group achieved HbA1c <7% compared to those receiving daily insulins. Regarding safety outcomes, insulin degludec had a lower incidence of both level 1 and level 2 or 3 hypoglycemia than the other three insulins. Insulin icodec showed a higher incidence of level 1 hypoglycemia than insulin glargine. Additionally, the incidence of AEs was higher with insulin icodec than with insulin degludec.
In patients with T2D, once-weekly insulin icodec may provide slightly better glycaemic control than daily insulin. Insulin icodec was more effective than insulin efsitora in reducing HbA1c levels; however, this benefit was offset by a significantly higher risk of level 1 hypoglycemia. The two insulins were comparable in terms of body weight change, glycemic target achievement, FPG reduction, and safety profiles, including level 2 or 3 hypoglycemia, AEs, and SAEs. Direct head to head RCTs are warranted to confirm these findings.
https://www.crd.york.ac.uk/PROSPERO/, identifier CRD420251177019.

PMID:
42666211
Bibliographic data and abstract were imported from PubMed on 29 Aug 2026.

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