Current Pharmaceutical Design - Volume 7, Issue 14, 2001

This review summarizes the results of clinical trials with the currently available insulin analogues (i.e., insulin lispro, insulin aspart, and insulin glargine) and evaluates their clinical benefit applying the standards of evidence-based medicine. All analogues show a more physiological time-action profile with either a shorter onset and shorter duration of action (insulin lispro and insulin aspart) or a more constant effect lastin Read More

For the past 75 years subcutaneous injections have been the only route of delivery of insulin therapy to diabetic patients. During this time, numerous attempts have been made to explore alternative routes for systemic insulin administration. However, thus far, no feasible other way of non-invasive insulin delivery has been developed. Dermal insulin application does not result in a reproducible and sufficient transfer of in Read More

Destruction and dysfunction of pancreatic beta-cells, resulting in absolute and relative insulin deficiency, represent key abnormalities in the pathogenesis of type 1 and type 2 diabetes, respectively. Following the discovery of amylin, a second beta-cell hormone that is co-secreted with insulin in response to nutrient stimuli, it was realized that diabetes represents a state of bihormonal beta cell deficiency and that lack of Read More

The loss of early insulin secretion appears to be a critical event in the deterioration in glucose tolerance during the development of type 2 diabetes. There is therefore a strong rationale for developing new antidiabetic agents aimed at restoring or replacing early prandial insulin secretion and thereby curbing mealtime glucose excursions in patients with type 2 diabetes. Four such new agents are either now available (repaglinid Read More

Glucagon-like peptide-1 (GLP-1) is released from gut endocrine cells following nutrient ingestion and acts to regulate nutrient assimilation via effects on gastrointestinal motility, islet hormone secretion, and islet cell proliferation. Exogenous administration of GLP-1 lowers blood glucose in normal rodents and in multiple experimental models of diabetes mellitus. Similarly, GLP-1 lowers blood glucose in normal subjects and in patient Read More

A variety of compounds containing an imidazoline ring have the ability to stimulate insulin secretion. Many of these also improve glycaemia in experimental models of type 2 diabetes and in man, suggesting that this class may be useful in the development of new orally active anti-diabetic drugs. However, the mechanisms by which imidazolines promote insulin secretion have not been clarified. The response does not appea Read More

In the early 1980s, an atypical beta-adrenergic receptor was discovered and subsequently called the beta3 -adrenoceptor (beta3 -AR). Agonists of the beta3 -AR were observed to simultaneously increase lipolysis, fat oxidation, energy expenditure and insulin action leading to the belief that this receptor might serve as an attractive target for the treatment of diabetes and obesity. In vivo studies lent credence to this postulate wit Read More

The inappropriate overproduction of glucose by the liver is one of the key contributors to the hyperglycaemia of the diabetic state, and thus is a logical site of intervention for novel anti-diabetic approaches. Metformin is the only currently marketed anti-hyperglycaemic drug whose action is attributed largely to its having inhibitory effects on hepatic glucose production, but its molecular site and mechanism(s) of action remain Read More