Insulin glargine and its place in the treatment of Types 1 and 2 diabetes mellitus

Abstract

Insulin treatment in Type 1 and Type 2 diabetes has come a long way since its discovery by Banting and Best in 1922. Early insulin therapy was life-saving, but was associated with practical problems and had side effects such as lipoatrophy. Initial modifications of insulin structure produced several classes of insulins with varying pharmacokinetics, but did not sufficiently mimic physiological insulin release. Novel long- and short-acting insulin analogues, the so-called 'designer insulins', developed through genetic engineering in the 1990s, paved the way for more physiological insulin therapy, which was theoretically less problematic in terms of hypoglycaemia and patient satisfaction. Insulin glargine (glargine) was the first DNA-recombinant long-acting insulin analogue. The replacement of asparagine with glycine and the addition of two arginine molecules in the molecular structure results in modified pharmacokinetics. Consequently, glargine has a longer, often 24-h profile, which is described as 'peakless' compared with other insulins such as neutral protamine Hagedorn insulin (NPH) and insulin ultralente. Since its launch, the use of glargine in Type 1 and Type 2 diabetes has been extensively reviewed to determine its place in the current insulin market. A potential advantage of glargine seems to be a lower risk of hypoglycaemia, particularly at night. The UK National Institute of Clinical Excellence has recommended that glargine is a treatment option for people with Type 1 diabetes. In Type 2 diabetes, it has been advised that glargine only be considered for: those who require assistance to administer insulin injections; those whose lifestyle is restricted significantly by recurrent symptomatic hypoglycaemic episodes; or those who would otherwise need twice-daily basal insulin injections in combination with oral glucose-lowering drugs.