Quo vadis nateglinide? Ten-year perspective.

It has been hypothesized that reducing postprandial glucose spikes would result both in improved overall glycemic control and long-term (especially cardiovascular) outcomes in patients with type 2 diabetes. Nateglinide, a short-acting insulin secretagogue of the meglitinide class of antidiabetic agents, has been marketed for the past decade specifically to address the diminished postprandial insulin secretion. It is thus timely to review our experience with this agent. This review summarizes findings from the key preclinical and pivotal clinical research studies that eventually led to drug approval. The literature search involved both original experimental studies and subsequent comprehensive reviews of the subject. The search included the databases (in English language) in the PubMed (maintained by the US Library of Medicine) domain as well as review of the articles in the author's files spanning the years 1995 - 2011. The author's subjective feelings about our understanding of the importance of controlling postprandial glucose excursions and what, if any, effect nateglinide has had in that respect since its introduction are given. Despite promising animal and human research data, no evidence has accumulated to date to suggest that addressing postprandial hyperglycemia with nateglinide (or any other antidiabetic medication for that matter) leads to improved outcomes in patients with type 2 diabetes mellitus.