Nateglinide, alone or in combination with metformin, is effective and well tolerated in treatment-nave elderly patients with type 2 diabetes
Diabetes and Glandular Disease Clinic, San Antonio, TX, USA. Diabetes Obesity and Metabolism
(Impact Factor: 6.36).
11/2007; 10(8):652-60. DOI: 10.1111/j.1463-1326.2007.00792.x
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.
Figures in this publication
Available from: Michelle A Baron
[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.
Vascular Health and Risk Management 02/2008; 4(6):1167-78.
[Show abstract] [Hide abstract]
ABSTRACT: To compare the effect of adding nateglinide or placebo on postprandial glucose excursions (PPGEs), glycated haemoglobin (HbA(1c)), diurnal glucose profiles and hypoglycaemia in patients with Type 2 diabetes treated with the combination of basal insulin and metformin.
This was an investigator-initiated, double-blind, randomized, parallel-group, study in five centres. Patients with Type 2 diabetes (n = 88, age 56.0 +/- 0.9 years, duration of diabetes 9.4 +/- 0.5 years, HbA(1c) 7.8 +/- 0.1%, body mass index 32.4 +/- 0.5 kg/m(2)) treated with basal insulin and metformin entered a 24-week period, during which basal insulin was titrated to optimize glucose control. Thereafter, the patients were randomized to receive either nateglinide (120 mg three times daily) or placebo before their main meals for 24 weeks.
During the optimization period, HbA(1c) decreased by -0.3 +/- 0.1 and -0.4 +/- 0.2% (NS) and insulin doses increased by 10.0 IU (2.0-32.0) [0.09 IU/kg (0.02-0.34)] and 10.0 IU (0.0-19.0) [0.11 IU/kg (0.0-0.25)] (NS) in the nateglinide and placebo groups. Mean postprandial glucose during weeks 20-24 averaged 9.0 +/- 0.3 and 10.0 +/- 0.3 mmol/l in the nateglinide and placebo groups (P = 0.025) and mean PPGE averaged 2.4 +/- 0.2 and 3.1 +/- 0.2 mmol/l, respectively (P = 0.019). At 24 weeks as compared with 0 weeks, mean HbA(1c) had decreased by 0.41 +/- 0.12% in the nateglinide group and by 0.04 +/- 0.12% in the placebo group (P = 0.023). The frequency of confirmed, symptomatic hypoglycaemia was 7.7 episodes/patient-year vs. 4.7 episodes/patient-year in the nateglinide and placebo groups (P = 0.031).
Addition of a short-acting insulin secretagogue at main meals improves postprandial hyperglycaemia during combination therapy with basal insulin and metformin, but increases the frequency of hypolycaemia.
Diabetic Medicine 05/2009; 26(4):409-15. DOI:10.1111/j.1464-5491.2009.02691.x · 3.12 Impact Factor
[Show abstract] [Hide abstract]
ABSTRACT: Insulin sensitivity and insulin secretion are reciprocally related such that insulin resistance is adapted by increased insulin secretion to maintain normal glucose and lipid homeostasis. Treatment of Type 2 diabetes should aim to restore and sustain the normal relationship between insulin sensitivity and secretion. Nateglinide is a rapid-onset, short-acting insulin-secretion enhancer that restores early-phase insulin secretion, reduces postprandial glucose excursions and prevents long-term hyperinsulinemia. Given its mechanism of action, it is evident that nateglinide would be more effective when used in combination with an insulin sensitizer, such as the thiazolidinediones. Thiazolidinediones do not stimulate insulin release and, therefore, are potentially suitable candidates for combination therapy with an insulin-secretion enhancer, such as nateglinide. Combination therapy of thiazolidinediones with nateglinide is effective, carries low risk of hypoglycemia and is suitable for patients with moderate renal impairment, although weight gain and edema are common side effects. Further studies are needed to determine whether nateglinide in combination with thiazolidinediones will help clinicians better achieve their treatment goals in targeting Type 2 diabetes. Moreover, comparative studies between nateglinide and medications targeting postprandial glycemia, such as dipeptidyl peptidase-4 inhibitors and glucagon-like peptide-1 analogues, are necessary. This article summarizes data concerning the mechanism of action, efficacy and safety of therapy with nateglinide and thiazolidinediones as monotherapy and in combination treatment, and aims at a better understanding of the substrate defects their synergy hopes to defy.
Expert Review of Endocrinology & Metabolism 10/2009; 4(6):537-552. DOI:10.1586/eem.09.40
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.