Insulin glargine: the first clinically useful extended-acting insulin in half a century?

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Abstract
Insulin glargine (HOE 901) appears to be the first clinically useful extended-acting insulin preparation for 50 years. A combination of a di-arginine addition to the C-terminal of the insulin B-chain, and a glycine substitution in the A-chain, produce an insulin which is soluble at acid pH, but precipitates in sc. tissue at neutral pH after injection. This new insulin analogue has slightly lower receptor binding affinity compared to human insulin, but equal potency in vivo. Prolonged receptor binding is not found, and IGF-1 binding is not significantly different from human insulin. Glucose clamp and sc. disappearance studies confirm that insulin glargine has a much slower onset of effect than NPH (Neutral Protamine Hagedorn) insulin, and a much more protracted profile of action. Variability of absorption is difficult to assess from published studies, but is not dissimilar to NPH insulin. Patient studies in Type 1 and Type 2 diabetes published to date are inconclusive, but appear to confirm differences in pharmacokinetics between insulin glargine and NPH, with significantly lower fasting plasma glucose levels or reduction in night hypoglycaemia. No safety concerns have emerged. It thus appears that insulin glargine is a genuinely new addition to the insulin family, and with further clinical experience it may well be possible to achieve better basal blood glucose control (without enhanced risk of hypoglycaemia), particularly at night or in conjunction with rapid-acting insulin analogues.