Effects of insulin regimens for type 2 diabetes mellitus: a systematic review and network meta-analysis

Insulin therapy is essential for managing hyperglycaemia in type 2 diabetes mellitus when oral or non-insulin injectable agents are no longer effective. However, the comparative effectiveness and safety of different insulin regimens remain uncertain. We aimed to compare the effects of basal, basal-bolus, biphasic and prandial insulin regimens on glycaemic management, weight, severe hypoglycaemia, insulin dose and quality of life in adults with type 2 diabetes.

We conducted a systematic review and network meta-analysis of RCTs. PubMed, EMBASE, the Cochrane Library and ClinicalTrials.gov were searched through to September 2025. The inclusion criteria for studies were RCTs enrolling adults with type 2 diabetes that compared at least two of the specified insulin regimens over ≥12 weeks. Pairs of reviewers independently screened studies, extracted data and assessed risk of bias using the Cochrane RoB-2 tool. Network meta-analyses were performed using a frequentist random-effects model, with basal insulin as the reference.

Fifty-eight RCTs involving 19,122 participants were included. Compared with basal insulin, HbA_1c reduction was -3.4 mmol/mol (95% CI -4.9, -1.9 mmol/mol) (-0.31% [95% CI -0.45%, -0.17%]) with a basal-bolus insulin regimen, -2.7 mmol/mol (95% CI -3.7, -1.6 mmol/mol) (-0.24% [95% CI -0.34%, -0.15%]) with biphasic insulin and -4.1 mmol/mol (95% CI -6.2, -2.1 mmol/mol) (-0.38% [95% CI -0.57%, -0.19%]) with prandial insulin. These results were classified as being of moderate confidence due to incoherence. All regimens were associated with approximately 30% increased probability of achieving HbA_1c target, 1 kg greater weight gain, and a borderline increase in the risk of severe hypoglycaemia. Insulin doses were slightly higher with basal-bolus and biphasic regimens. Quality-of-life data were limited. Subgroup analyses for insulin initiation and intensification yielded consistent results.

Complex insulin regimens provide modest glycaemic benefits over basal insulin but are associated with greater weight gain and a suggested higher risk of hypoglycaemia. These results are based on evidence of moderate confidence. These trade-offs support the need for individualised regimen selection, informed by clinical context, patient preferences and treatment goals.

PROSPERO registration no. CRD42020181473.

This research was supported by the Committee for the Development of Higher Education Personnel (CAPES) and the Hospital de Clínicas de Porto Alegre - FIPE HCPA.