Once-weekly versus once-daily basal insulin in adults with type 2 diabetes: a systematic review and meta-analysis of randomized trials

Background Although once-weekly (OW) basal insulins have emerged as a novel therapeutic option for type 2 diabetes mellitus (T2DM), comparative evidence against once-daily (OD) regimens remains inconclusive. Thus, this systematic review and meta-analysis aimed to evaluate the comparative efficacy and safety of OW versus OD basal insulins in individuals with T2DM. Methods Randomized controlled trials (RCTs) that compared OW versus OD insulin regimens in T2DM were retrieved through searching PubMed, Embase, Scopus, and Web of Science. The primary outcome was the change in HbA1c (%). A random-effects model was applied for analysis. Results A total of 15 RCTs comprising 8,666 participants were included. Compared to OD insulin, OW insulin significantly lowered HbA1c (mean difference (MD) -0.14%, [95% confidence interval (CI) -0.20; -0.08], p < 0.0001, I 2 = 43.10%) and increased the proportion of patients achieving HbA1c <7.0% (relative risk (RR) 1.12, [95% CI 1.02; 1.23], p = 0.014). However, OW insulin was associated with modest weight gain (MD 0.40 kg, [95% CI 0.22; 0.58], p < 0.0001), a higher risk of hypoglycemia level 1 (RR: 1.16, [95% CI 1.06; 1.27], p = 0.0014), and a higher risk of any adverse events (RR 1.04, [95% CI 1.00; 1.09], p = 0.044). Other clinical outcomes, including fasting plasma glucose, and safety outcomes were similar between the two groups. Subgroup meta-analysis showed better glycemic control through a significant reduction in HbA1c with icodec (MD: -0.19, 95% CI [-0.27; -0.11], I 2 = 45.8%); however, no statistical difference was observed after efsitora or insulin GZR4. Additionally, there was no subgroup difference based on type of OD insulin [degludec vs. glargine ( P interaction = 0.55)] or type of patients [naïve patients vs. patients previously treated with basal insulin ( P interaction = 0.49)]. Conclusions Among patients with T2DM, OW insulin was associated with a modest, statistically significant reduction in HbA1c compared with OD regimens; however, this effect was largely driven by insulin icodec, and its clinical significance remains uncertain. These findings were accompanied by slight weight gain and an increased risk of mild hypoglycemia. Systematic review registration https://www.crd.york.ac.uk/PROSPERO/ , identifier CRD420251018849.