Oral repaglinide (GlucoNorm®; NovoNorm®; Prandin®; Surepost®) is a rapid-acting insulin secretagogue that lowers postprandial glucose (PPG) excursions by targeting early-phase insulin release, with reductions in PPG considered to be important in reducing long-term cardiovascular complications of diabetes mellitus. Repaglinide, a carbamoylbenzoic acid derivative, is chemically related to the meglitinide class of insulin secretagogues, but unrelated to the sulfonylurea insulin secretagogues. Meglitinides, including repaglinide, have a distinct binding site at the β-cell membrane, which differs from that of sulfonylureas, and corresponds to greater insulinotropic effects with repaglinide than with glibenclamide and/or glimepiride and a more rapid onset of action in in vitro and in vivo studies. This article reviews the clinical efficacy and tolerability of oral repaglinide in the treatment of patients with type 2 diabetes and provides an overview of its pharmacological properties.
In well designed clinical trials of up to 52 weeks’ duration and in the clinical practice setting, recommended dosages of repaglinide (0.5–4mg three times daily up to 30 minutes prior to a meal) provided effective glycaemic control and were generally well tolerated in treatment-naive or -experienced adult patients with type 2 diabetes, including elderly patients and those with renal impairment. Furthermore, as monotherapy or in combination with other oral antihyperglycaemic drugs, repaglinide was at least as effective as other oral antihyperglycaemic drugs at improving or maintaining glycaemic control, with a tolerability profile that was generally similar to that of sulfonylurea drugs and nateglinide. Thus, repaglinide remains an effective option for the management of patients with type 2 diabetes.
Various sections of the manuscript reviewed by:
G. Bertino, Haematology Unit, Department of Internal Medicine and Systemic Diseases, University of Catania-Italy Policlinic, Catania, Italy; G. Dimitriadis, Attikon University Hospital, Second Department of Internal Medicine, Research Institute and Diabetes Center, University of Athens Medical School, Athens, Greece; J. Ducobu, Universite de Mons-Hainaut, Mons, Belgium; T. Levien, Department of Pharmacotherapy, Washington State University Spokane, Spokane,WA, USA; K. Whalen, Department of Pharmacotherapy and Translational Research, University of Florida College of Pharmacy, Gainesville, FL, USA.
Sources: Medical literature (including published and unpublished data) on ‘repaglinide’ was identified by searching databases since 1996 (including MEDLINE and EMBASE and in-house AdisBase), bibliographies from published literature, clinical trial registries/databases and websites (including those of regional regulatory agencies and the manufacturer). Additional information (including contributory unpublished data) was also requested from the company developing the drug.
Search strategy: MEDLINE, EMBASE and AdisBase search terms were ‘repaglinide’ and (‘diabetes mellitus, type 2’ or ‘non insulin dependent diabetes mellitus’ or ‘type 2 diabetes mellitus’). Searches were last updated 10 Jan 2012.
Selection: Studies in patients with type 2 diabetes mellitus who received repaglinide. Inclusion of studies was based mainly on the methods section of the trials. When available, large, well controlled trials with appropriate statistical methodology were preferred. Relevant pharmacodynamic and pharmacokinetic data were also included.
Index terms: Repaglinide, meglitinide, insulin secretagogues, type 2 diabetes mellitus, pharmacodynamics, pharmacokinetics, therapeutic use, tolerability.