Understanding concentrated insulins: a systematic review of randomized controlled trials

Area of Science:

• Endocrinology
• Pharmacology

Background:

• Concentrated insulins, with concentrations exceeding 100 units/mL, represent a class of antidiabetic agents.
• Their development aims to address specific patient needs, potentially including those with higher insulin requirements.

Purpose of the Study:

• To systematically review and synthesize evidence from randomized controlled trials on concentrated insulins.
• To provide clinical guidance for the appropriate utilization of these high-concentration insulin formulations.

Main Methods:

• Comprehensive literature searches were performed across multiple databases (Medline, Embase, Cochrane) and clinical trial registries.
• Included studies were phase 1-4 randomized controlled trials evaluating subcutaneously administered concentrated insulins.
• Study quality was assessed, and trial registration data were cross-referenced.

Main Results:

• Thirty-eight trials involving 7900 participants and 34 publications were analyzed, evaluating four marketed concentrated insulins.
• Bioequivalence was established for insulin degludec 200 units/mL and insulin lispro 200 units/mL compared to their 100 units/mL counterparts.
• Efficacy studies demonstrated noninferior glycemic control with low rates of severe hypoglycemia for basal and prandial/basal concentrated insulins.

Conclusions:

• Concentrated insulin products offer efficacious and safe therapeutic options when used in appropriate patient populations.
• Key considerations for clinical practice include patient-specific factors, insulin dosing requirements, and product characteristics such as potency and device features.