Nateglinide - current and future role in the treatment of patients with type 2 diabetes mellitus

Abstract

Therapy for type 2 diabetes mellitus should aim to control not only fasting, but also postprandial glucose levels. Nateglinide, a d-phenylalanine derivative, restores postprandial early phase insulin secretion in a transient and glucose-sensitive manner without affecting basal insulin levels. As nateglinide is administered immediately before meals it provides greater lifestyle flexibility than agents that require patients to eat to avoid hypoglycemic events (e.g. long-acting sulfonylureas). In randomised, double-blind trials in patients with type 2 diabetes, nateglinide monotherapy (mealtime treatment of 120 mg three times daily) significantly improved long-term glycaemic control by significantly reducing glyated haemoglobin (HbA 1c) and preventing mealtime glucose spikes. The combination of nateglinide with insulin-sensitising agents, for example, metformin and thiazolidinediones, addresses the dual defects of loss of insulin secretion and insulin resistance to provide optimal management of type 2 diabetes, and more patients achieve HbA 1c goal with nateglinide combination therapy rather than with monotherapy with other oral agents. Nateglinide also restores early insulin secretion and reduces postprandial hyperglycaemia in prediabetic subjects with impaired glucose tolerance (IGT) and appears similarly effective in elderly and non-elderly populations with type 2 diabetes. It has an excellent safety and tolerability profile, with a low propensity to cause hypoglycaemia due to its transient, selective effect on early phase insulin secretion. Nateglinide as monotherapy or combination therapy is an effective option to reduce mealtime glucose in patients with type 2 diabetes. The results of ongoing research into its potential role in delaying progression to overt diabetes, and protecting against cardiovascular events, in prediabetic patients with IGT are awaited.

Pharmacology and therapeutic implications of current drugs for type 2 diabetes mellitus

“…The class takes its name from the meglitinide moiety of glibenclamide, which exerts an insulin-releasing effect independently of the sulfonyl moiety 26,28,81 .…”

Diabetes mellitus – an overview

“…Adverse effects of Starlix include weight gain, hyperinsulinaemia and hypoglycaemia. These drugs should be used with caution in patients with hepatic or renal insuffi ciency, because delayed excretion of the drug, resulting in its accumulation, may cause hypoglycaemia [96].…”

Early diagnosis and treatment of steroid-induced diabetes mellitus in patients with rheumatoid arthritis and other connective tissue diseases

“…Nateglinide also improves postprandial hyperglycemia [9,10]. In a Darnish retrospective study, repaglinide (a glinide) did not increase the incidence of cardiovascular events compared with the incidence associated with metformin use [16].…”

“…However, aggravated postprandial glycemia increases the risk of event development compared with high fasting glucose levels in DM patients [6][7][8]. Nateglinide, which stimulates the release of insulin from the pancreas, and acarbose, which is an inhibitor of alpha-glucosidase, are used for the treatment of postprandial hyperglycemia and type II DM [9][10][11][12].…”