Type 2 diabetes mellitus (T2DM) is characterized by
hyperglycemia due to a combination of
insulin resistance and impaired insulin secretion. The
hyperglycemia is associated with an increased risk for micro- and macrovascular complications, and lowering fasting and
postprandial hyperglycemia may be protective against these complications.
Repaglinide is an
insulin secretagogue that lowers
blood glucose levels in patients with T2DM. We review the effects of
repaglinide in patients with T2DM, its impact on glycemia and its non-glycemic effects, and its effects when used in special situations or patient populations. Results from randomized controlled trials, observational studies, and safety reports involving humans and published in the English-language through 1 May 2007 identified by a search in PubMed/MEDLINE were evaluated. Present knowledge indicates that
repaglinide reduces fasting and
postprandial hyperglycemia and the level of
glycosylated hemoglobin (HbA1c) in patients with T2DM. It is at least as effective in reducing HbA1c and fasting plasma
glucose as sulphonylureas,
metformin, or the
glitazones and in combination
therapy with other drugs,
repaglinide is as effective as any other combination. Some studies show a better effect of
repaglinide on postprandial glycemia than the comparators. Its propensity to induce
hypoglycemia is similar to or a little less than that of sulphonylureas.
Repaglinide is associated with less
weight gain than sulphonylureas and the
glitazones.
Repaglinide has primarily a role in the treatment of T2DM when
metformin cannot be used due to adverse effects, when
metformin fails to adequately
control blood glucose levels, when there is a need for flexible dosing (i.e. the elderly or during Ramadan fasting), or when there is a specific wish to lower postprandial
glucose.
Repaglinide may also have an advantage when an oral agent is needed in diabetic patients with renal impairment. Because of its short duration of action,
repaglinide should be taken before each meal, usually at least three times a day. Although no study has investigated whether
repaglinide lowers total mortality or cardiovascular endpoints, several studies indicate beneficial effects on cardiovascular
surrogate endpoints, such as carotid intima-media thickening, markers of
inflammation, platelet activation,
lipid parameters, endothelial function,
adiponectin, and oxidative stress. In conclusion,
repaglinide is a compound that can be used in both mono- and combination
therapy for the treatment of both fasting and
postprandial hyperglycemia in patients with T2DM. It can be used in patients at different stages of the disease, from uncomplicated to severe renal impairment. Although the
drug has been tested in a large number of clinical trials and observational studies, its world-wide use is far less than, for example, sulphonylureas.
Repaglinide may offer an additional potential for lowering
blood glucose levels in T2DM that until now has not been fully realized by many clinicians.