Nateglinide, alone or in combination with metformin, is effective and well tolerated in treatment-nave elderly patients with type 2 diabetes

ArticleinDiabetes Obesity and Metabolism 10(8):652-60 · November 2007with4 Reads
DOI: 10.1111/j.1463-1326.2007.00792.x · Source: PubMed
Abstract
The aim of this work was to assess the efficacy and tolerability of nateglinide alone or in combination with metformin in elderly patients with type 2 diabetes (T2DM). Study 1 was a 12-week, multicentre, randomized, double blind and placebo-controlled study of nateglinide monotherapy (120 mg, before meals) in 66 drug-naïve patients with T2DM aged >or=65 years. Study 2 was a 104-week, multicentre, randomized, double blind and active-controlled study of nateglinide (120 mg, before meals) or glyburide (up to 5 mg bid) in combination with metformin (up to 1000 mg bid) in 69 treatment-naïve patients with T2DM aged >or=65 years. HbA(1c), fasting and postprandial glucose levels, and safety assessments were made. In Study 1, nateglinide significantly reduced HbA(1c) from baseline (7.6 +/- 0.1% to 6.9 +/- 0.1%; Delta = -0.7 +/- 0.1%, p < 0.001) and compared with placebo (between-group difference = -0.5%, p = 0.004 vs. nateglinide). No hypoglycaemia was reported. In Study 2, combination therapy with nateglinide/metformin significantly reduced HbA(1c) from baseline (7.8 +/- 0.2% to 6.6 +/- 0.1%; Delta = -1.2 +/- 0.2%, p < 0.001), as did glyburide/metformin (7.7 +/- 0.1% to 6.5 +/- 0.1%; Delta = -1.2 +/- 0.1%, p < 0.001). There was no difference between treatments (p = 0.310). One nateglinide/metformin-treated patient experienced a mild hypoglycaemic episode compared with eight episodes in eight patients on glyburide/metformin; one severe episode led to discontinuation. Target HbA(1c) (<7.0%) was achieved by 60% of patients receiving nateglinide (Study 1) and 70% of nateglinide/metformin-treated patients (Study 2). Initial drug treatment with nateglinide, alone or in combination with metformin, is well tolerated and produces clinically meaningful improvements in glycaemic control in elderly patients with T2DM.
    • "The major goal in the management of diabetes is to maintain blood sugar level as close to normal as possible [14] . Interestingly, insulin secretion was significantly greater when nateglinide was taken before a meal compared to nateglinide given in the fasted state or in response to just the meal [15] Nateglinide is associated with a low risk of hypoglycemic events in placebo-controlled or active-controlled studies [16][17]Nateglinide had more pronounced effects on reducing fasting plasma glucose and glucagon secretion, with no differences in post-prandial glucose and insulin secretion [18] No major hypoglycaemic episodes and no reported minor hypoglycaemic events were found in the nateglinide group in a randomized, multicenter study, where patients were randomized to receive monotherapy with nateglinide [19] . "
    [Show abstract] [Hide abstract] ABSTRACT: Background-Continual hyperglycaemia is a well-known risk factor in type-2 diabetics for the micro-and macrovascular complications. There are a variety of drugs available for the treatment of type-2 diabetes and no fixed regime possible, which fits all. Therefore choosing an appropriate anti-diabetic agent from the available groups is a tricky process for prescribers. To this purpose, we studied the nateglinide versus glimepiride monotherapy in type-2 diabetes patients in a tertiary care hospital. Method-The present prospective study was conducted to compare the effect of glimepiride and nateglinide in all patients with type – 2 diabetes attending general medicine OPD for three months between March 2011 to May 2011 at tertiary care hospital, Puducherry. The total number of patients was 40, equally divided into two groups. Fasting blood sugar with 140 to 220 mg/dl were included, and patients with diabetic complications and hepatic and renal disorders were excluded from the study. Group I consists of 20 newly diagnosed type – 2 DM taking glimepiride 1 mg and group-2 consists of 20 newly diagnosed type – 2 DM taking Nateglinide monotherapy 60mg once daily laboratory parameters like FBS, PPBS, HbA1c and lipid profile and have been measured before and after study. The study continued for three months and every two weeks; FBS and PPBS were measured. Mean, SD, and percentages were used to describe the data. Chi-square and unpaired "t" test were used appropriately as inferential tools. P value <0.0.5 was considered statistically significant. Results-The mean change in FBS was 18.55% with the treatment group taking glimepiride 1mg and the mean change in FBS with nateglinide group was 22.35%.The mean change in PPBS was 16.78% in treatment with glimepiride 1mg group, and the mean change in PPBS in nateglinide was 22%. Mean change in the glycosylated haemoglobin was 10.5% with the group taking glimepiride and was with patient taking nateglinide was 16.49%. Conclusion-It was obvious that both glimepiride and nateglinide are effective, but the decrease in PPBS and HbA1c% was more with nateglinide. A further study in the large population is essential to assess long-term postprandial glucose control and relationship to diabetic complications.
    Full-text · Article · Jan 2016 · Vascular Health and Risk Management
    • "A double blind, multicenter, randomized study that aimed to assess the efficacy and tolerability of nateglinide alone or in combination with metformin in elderly patients with T2DM demonstrated that nateglinide monotherapy (120 mg) did not cause any serious hypoglycemic episodes. In the nateglinide/metformin arm there was one mild hypoglycemic episode compared with eight episodes in the glyburide/metformin arm [49]. Studies directly comparing repaglinide and nateglinide have been lacking and it is therefore not possible to assess their differences in term of clinical efficacy and safety [37, 67]. "
    [Show abstract] [Hide abstract] ABSTRACT: Type 2 diabetes mellitus (T2DM) is one of the most common chronic diseases worldwide, presenting a great challenge to the public health systems due to high morbidity and mortality, because of frequent micro-/macro-vascular complications. Many treatment options are now available, with different efficacy as well as mechanisms of action to improve deranged glucose metabolism. We review some of the available data on derivatives of meglitinide, namely nateglinide and repaglinide. These two compounds increase insulin secretion by a mechanism similar to the one of sulfonylureas, but with a shorter half-life. Nateglinide and repaglinide, derivatives of meglitinides, have characteristic pharmacodynamic and pharmacokinetic properties that, together with their proposed mechanism of action, make them useful for type 2 diabetes mellitus, especially when used in combination therapy.
    Full-text · Article · Oct 2013
  • [Show abstract] [Hide abstract] ABSTRACT: The increasing prevalence of type 2 diabetes provides impetus for both development of new drugs to improve glycemic control and for reconsideration of treatment strategies with existing agents. Combination therapy with complementary drug classes that act on different aspects of glycemic control has been a particularly effective strategy. This work reviews the published literature reporting efficacy and safety/tolerability of nateglinide, a rapid-onset insulinotropic agent with a predominant effect to reduce postprandial glucose, when combined with metformin, a first-line agent that suppresses hepatic glucose production and thereby reduces fasting plasma glucose. The nateglinide/metformin combination has consistently been found to be both efficacious and well tolerated, whether given as initial combination therapy in drug-naïve patients or when added to metformin monotherapy. Maximum efficacy (Δ glycosylated hemoglobin [HbA1c]= −1.4% to −1.9%, sustained for up to 2 years of treatment) was seen in studies of drug-naïve patients in whom pharmacotherapy was initiated with the combination of nateglinide and metformin, and modest reductions in HbA1c (Δ = −0.5% to −1.2%, sustained for up to 24 weeks) were found when nateglinide was added to ongoing metformin monotherapy. Conclusion: the combination of nateglinide and metformin provides a sustained degree of glycemic control not achievable with either agent given as monotherapy.
    Full-text · Article · Feb 2008
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