IntroductionThis study compared basal analog (BA: glargine U100/mL and detemir) and premix (PM: human, lispro and aspart biphasic) insulin regimens in terms of their efficacy and safety in type 2 diabetes mellitus patients.MethodsSearches of MEDLINE, Embase, and CENTRAL identified primary randomized controlled trials (RCTs) ≥ 12 weeks in duration that compared BA or PM insulin regimens in adults with T2DM, with ≥ 30 patients per arm. A systematic literature review and a pairwise meta-analysis were performed using a random effects model adjusted for between-study variability. Analyses were conducted based on frequency of bolus insulin and PM injections, PM ratio and type, BA type, race, follow-up period, and baseline glycosylated hemoglobin (HbA1c).ResultsTwenty-two primary RCTs with 9691 patients were included. The BA and PM regimens yielded similar changes in HbA1c and postprandial glucose levels, with a statistically significant reduction in fasting glucose [mean difference (MD) − 0.61 mmol/L (95% confidence interval (CI) − 0.90, − 0.32), I2 = 89.6%]. The BA regimens showed significantly reduced rates of total hypoglycemia [odds ratio (OR) 0.77 (95% CI 0.64, 0.92), I2 = 65.3%] and changes in body weight [MD − 0.48 kg (95% CI − 0.86, − 0.11), I2 = 75.7%] compared to PM regimens. Stratification by PM type and dosing ratio demonstrated statistically significant reductions in HbA1c favoring BA compared to human [MD − 0.39% (95% CI − 0.60, − 0.18), I2 = 61.8%] or 50/50-ratio [MD − 0.22% (95% CI − 0.40, − 0.04), I2 = 0.0%] PM regimens. Other subgroup analyses found no difference in HbA1c change between the BA and PM regimens.ConclusionWhen compared to PM regimens, BA regimens yielded similar efficacies and better safety profiles in patients with type 2 diabetes mellitus.FundingSanofi (Shanghai, China).Electronic supplementary materialThe online version of this article (10.1007/s13300-019-0606-6) contains supplementary material, which is available to authorized users.