Glycemic control and weight loss benefits of fixed-ratio combinations of basal insulins and GLP1 receptor agonists in type 2 diabetes: A systematic review and network meta-analysis

Purpose To compare glycemic and weight effects of fixed-ratio combinations (FRCs) of basal insulin (BI) and glucagon-like peptide-1 receptor agonists (GLP1RAs) in adults with type 2 diabetes (T2D). Methods Randomized controlled trials of BI–GLP1RA FRCs in adults with T2D were identified across major databases through 20 December 2025. Co-primary outcomes were changes in glycated hemoglobin (HbA1c) and body weight. A frequentist random-effects network meta-analysis, with BI as the reference, was conducted in R using netmeta. Certainty was assessed using Confidence in Network Meta-Analysis (CINeMA). Results Thirty trials involving 17,862 participants were included. All FRCs reduced HbA1c and body weight more than BI alone. For HbA1c, HR17031 had the largest estimated reduction (mean difference [MD]: -0.72%), followed by IDegLira (-0.64%) and iGlarLixi (-0.53%). For body weight, IcoSema had the largest estimated reduction (-3.16 kg), followed by HR17031 (-1.74 kg) and IDegLira (-1.65 kg). No HR17031 comparison with other FRCs was statistically significant for either co-primary outcome; its ranking is hypothesis-generating. Excluding the high-risk-of-bias trial produced broadly consistent estimates. Compared with BI, FRCs increased achievement of HbA1c < 7%, often without weight gain or clinically significant/severe hypoglycemia. CINeMA indicated predominantly low- to moderate-certainty evidence for FRC versus BI comparisons and low- to very low-certainty evidence for many indirect comparisons among active regimens. Conclusions BI–GLP1RA FRCs improve glycemic control and weight outcomes compared with BI alone. Rankings and apparent differences among FRCs or versus other active regimens warrant cautious interpretation given heterogeneity, inconsistency, and limited certainty of indirect evidence.