Efficacy and Safety of Basal Analog Regimens in Type 2 Diabetes Mellitus: Systematic Review and Meta-Analysis of Randomized Controlled Trials

Abstract

Introduction This 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. Methods Searches 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). Results Twenty-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), I 2 = 89.6%]. The BA regimens showed significantly reduced rates of total hypoglycemia [odds ratio (OR) 0.77 (95% CI 0.64, 0.92), I 2 = 65.3%] and changes in body weight [MD − 0.48 kg (95% CI − 0.86, − 0.11), I 2 = 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), I 2 = 61.8%] or 50/50-ratio [MD − 0.22% (95% CI − 0.40, − 0.04), I 2 = 0.0%] PM regimens. Other subgroup analyses found no difference in HbA1c change between the BA and PM regimens. Conclusion When compared to PM regimens, BA regimens yielded similar efficacies and better safety profiles in patients with type 2 diabetes mellitus. Funding Sanofi (Shanghai, China). Electronic supplementary material The online version of this article (10.1007/s13300-019-0606-6) contains supplementary material, which is available to authorized users.

Italian guidelines for the treatment of type 2 diabetes

“…Available data suggest that different long-acting insulin formulations are associated with different risk of hypoglycemia in type 2 diabetes 56 − 59 …”

Comparative efficacy and safety of Gla‐300 versus IDegAsp in insulin‐naïve people with type 2 diabetes mellitus uncontrolled on oral anti‐diabetics

“…To our knowledge, no previous ITC has compared Gla‐300 to IDegAsp. However, a previous SLR/NMA comparing basal analogue (Gla‐100 and detemir) and premix regimens showed similar changes in HbA1c and PPG levels 24 . Furthermore, the basal analogue regimens showed significantly lower rates of total hypoglycaemia and changes in body weight compared with premix regimens.…”

“…However, a previous SLR/NMA comparing basal analogue (Gla-100 and detemir) and premix regimens showed similar changes in HbA1c and PPG levels. 24 Furthermore, the basal analogue regimens showed significantly lower rates of total hypoglycaemia and changes in body weight compared with premix regimens. The lower risk of any hypoglycaemia and confirmed (PG <3.0-3.1 mmol/L) hypoglycaemia with Gla-300 compared with IDegAsp in our study is consistent with this previous research.…”

A Japanese Study Assessing Glycemic Control with Use of IDegAsp Co-formulation in Patients with Type 2 Diabetes in Clinical Practice: The JAGUAR Study

“…Patients switched from either pre-mixed insulin, basal–bolus insulin, or basal insulin. Considering basal–bolus insulin is efficacious in reducing HbA 1c [ 22 ], the substantial improvement in glycemic control despite many patients switching from this regimen may not be expected. However, patients included in this real-world study had likely been switched because their regimen was not adequate for their requirements.…”