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Aim: To compare the efficacy and safety of insulin glargine‐300 once daily (Gla‐300) with insulin degludec/aspart (IDegAsp) once daily in patients with type 2 diabetes (T2D) inadequately controlled on oral anti‐diabetic drugs (OADs). Materials and methods: A systematic literature review of randomized controlled trials was followed by an indirect treatment comparison of studies involving insulin naïve adults, inadequately controlled [glycated haemoglobin (HbA1c) ≥7.0%] on OADs, who received Gla‐300 or IDegAsp once daily. Outcomes of interest were change in HbA1c, blood glucose, weight and insulin dose, as well as incidence and event rate of hypoglycaemia and other adverse events. Results: Four trials with broadly similar baseline patient characteristics were included in the meta‐analyses and indirect treatment comparison. At 24‐28 weeks, the indirect comparison of Gla‐300 to IDegAsp once daily estimated no statistically significant difference for change in HbA1c (%) from baseline [mean difference of 0.10% (95% CI: −0.20, 0.39; p =.52)]; a statistically significant mean difference of −1.31 kg (95% CI: −1.97, −0.65; p <.05) for change in body weight from baseline; statistically significant odds ratios of 0.62 (95% CI: 0.41, 0.93; p <.05) for incidence of any hypoglycaemia; and 0.47 (95% CI: 0.25, 0.87; p <.05) for incidence of anytime confirmed hypoglycaemia (plasma glucose <3.0‐3.1 mmol/L). No significant differences were observed for insulin dose and adverse events. Conclusion: In insulin‐naïve patients with T2D inadequately controlled on OADs, commencing Gla‐300 shows a comparable HbA1c reduction, but with significantly less weight gain and a lower incidence of any and confirmed hypoglycaemia compared with commencing IDegAsp. [ABSTRACT FROM AUTHOR]