Nateglinide
Regulatory sources consulted
Approved indications
- Adjunct to diet and exercise to improve glycaemic control in adults with type 2 diabetes mellitus.
Contraindications
Absolute
- Hypersensitivity to nateglinide or any excipient.
- Type 1 diabetes mellitus with negative C-peptide.
- Diabetic ketoacidosis, with or without coma.
- Pregnancy and breastfeeding.
- Severe hepatic impairment.
Clinical warnings
- Major warning · It can cause hypoglycaemia and hypersensitivity reactions. — CIMA STARLIX, registro 01174012
- Major warning · Severe renal impairment without haemodialysis increases susceptibility to hypoglycaemia; consider discontinuation if the hypoglycaemic effect is potentiated. — https://cima.aemps.es/cima/dochtml/ft/01174012/FT_01174012.html
Drug interactions
- ModerateMedicines that increase the hypoglycaemic effect
Mechanism: ACE inhibitors, NSAIDs, salicylates, MAO inhibitors, non-selective beta-blockers, anabolic hormones, and strong CYP2C9 inhibitors may increase or prolong the hypoglycaemic effect.
Recommendation: Closely monitor blood glucose when starting or stopping these medicines and adjust nateglinide if needed.
https://cima.aemps.es/cima/dochtml/ft/01174012/FT_01174012.htmlCIMA registro 01174012
- ModerateMedicines that reduce the hypoglycaemic effect
Mechanism: Diuretics, corticosteroids, beta-2 agonists, somatropin, somatostatin analogues, rifampin, phenytoin, and St John's wort may reduce the hypoglycaemic effect.
Recommendation: Closely monitor blood glucose when starting or stopping these medicines and adjust nateglinide if needed.
https://cima.aemps.es/cima/dochtml/ft/01174012/FT_01174012.htmlCIMA registro 01174012
Adverse events
Common (≥1%)
Hypoglycaemia · Abdominal pain · Diarrhoea · Dyspepsia · Nausea
Rare but serious
Severe hypoglycaemia · Hypersensitivity reaction · Elevated liver enzymes · Erythema multiforme
Pregnancy and lactation
Nateglinide is contraindicated during pregnancy and breastfeeding.
Recent literature (PubMed)
Available data on the effects of anti-diabetic drugs on fracture risk are contradictory. Therefore, our study aimed to analyze all available data on the effects of anti-diabetic drugs on fracture risk in type 2 diabetes mellitus (T2DM) patients. Embase, Medline, ClinicalTrials.gov, and Cochrane CENTRAL were searched for relevant trials. All data analyses were performed with STATA (12.0) and R language (3.6.0). Risk ratio (RR) with its 95% confidence interval (CI) was calculated by combining data for the fracture effects of anti-diabetic drugs, including sodium-glucose co-transporter 2 (SGLT2) inhibitors, dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, meglitinides, α-glucosidase inhibitors, thiazolidinediones, biguanides, insulin, and sulfonylureas. One hundred seventeen eligible randomized controlled trials (RCTs) with 221,364 participants were included in this study. Compared with placebo, trelagliptin (RR 3.51; 1.58-13.70) increased the risk of fracture, whereas albiglutide (RR 0.29; 0.04-0.93) and voglibose (RR 0.03; 0-0.11) decreased the risk of fracture. Other medications were comparable in terms of their effects on fracture risk, and no statistical significance was observed. In terms of fractures, voglibose (0.01%) may be the safest option, and trelagliptin (13.64%) may be the worst. Sensitivity analysis results were consistent with those of the main analysis. No statistically significant differences were observed in the regression coefficients of age (1.03; 0.32-2.1), follow-up duration (0.79; 0.27-1.64), and sex distribution (0.63; 0.15-1.56). We found varied results on the association between the use of anti-diabetic drugs and fracture risk. Specifically, trelagliptin raised the risk of fracture, whereas voglibose and albiglutide showed benefit with statistical difference. Other drugs were comparable in terms of their effects on fracture risk. Some drugs (omarigliptin, sitagliptin, vildagliptin, saxagliptin, em
The progression of carotid intima-media thickness (cIMT) can partially predict the occurrence of future cardiovascular events. This network meta-analysis compared the effects of 14 antidiabetic drugs (acarbose, alogliptin, exenatide, glibenclamide, glimepiride, ipragliflozin, metformin, nateglinide, pioglitazone, rosiglitazone, sitagliptin, tofoglifozin, troglitazone, voglibose) on the progression of cIMT. PubMed, EMBASE, Cochrane Library, and Web of Science were searched to screen all clinical trials of treatment of cIMT with hypoglycemic agents before March 1, 2024. The differences in the changes in cIMT between the treatment group and control group were evaluated. After screening 8395 citations, 25 studies (6675 patients) were included. The results indicated that exenatide had the best efficacy in slowing down cIMT progress, and exenatide [MD=-0.13,95%CI (-0.25, -0.01)], alogliptin [MD=-0.08,95%CI (-0.13, -0.02)] and metformin [MD=-0.05, 95%CI (-0.09, -0.02)] are more effective than placebo. Long-term treatment of exenatide, alogliptin, and metformin may be more effective than other hypoglycemic drugs in slowing the progression of cIMT. https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42024519474.
Nateglinide belongs to the meglitinide class of insulin secretagogues. It is used as an oral hypoglycemic agent for the treatment of type 2 diabetes mellitus. Nateglinide is an amino acid derivative of D-phenylalanine that binds to the ATP-sensitive potassium channels in pancreatic beta cells and stimulates the secretion of insulin. In this chapter, various aspects of Nateglinide are discussed. This includes methods used for its synthesis, physicochemical properties, and different techniques employed to determine its structure, such as elemental analysis, IR, UV, (1H and 13C) NMR, MS, and XRD. Additionally, the chapter covers a literature review of various methods of analysis of Nateglinide, such as X-ray powder diffraction pattern analysis, differential scanning calorimetry, spectrophotometric, chromatographic, capillary electrophoresis and immunoassay methods. Moreover, the pharmacology of the title drug including pharmacokinetics, pharmacodynamics, mechanism of action, drug-drug and drug-food interactions are also reviewed.
To elucidate the long-term cardiovascular benefit of lowering postprandial hyperglycemia (PPG) in early-stage T2DM patients. This 10-year post-trial follow-up study included 243 patients from the DIANA (DIAbetes and diffuse coronary Narrowing) study, a multi-center randomized controlled trial which compared the efficacy of one-year life-style and pharmacological (voglibose/nateglinide) intervention lowering PPG on coronary atherosclerosis in 302 early-stage T2DM subjects [impaired glucose tolerance (IGT) or newly-diagnosed T2DM] (UMIN-CTRID#0000107). MACE (all-cause death, non-fatal MI or unplanned coronary revascularization) were compared in (1) three assigned therapies (life-style intervention/vogliose/nateglinide) and (2) patients with and without improvement of PPG (reversion from IGT to NGT or from DM to IGT/NGT on 75 g oral glucose tolerance test). During the 10-year post-trial observational period, voglibose (HR = 1.07, 95%CI: 0.69-1.66, p = 0.74) or nateglinide (HR = 0.99, 95%CI: 0.64-1.55, p = 0.99) did not reduce MACE. Similarly, achieving the improvement of PPG was not associated with a reduction of MACE (HR = 0.78, 95%CI: 0.51-1.18, p = 0.25). However, in IGT subjects (n = 143), this glycemic management significantly reduced the occurrence of MACE (HR = 0.44, 95%CI: 0.23-0.86, p = 0.01), especially unplanned coronary revascularization (HR = 0.46, 95%CI: 0.22-0.94, p = 0.03). The early improvement of PPG significantly reduced MACE and unplanned coronary revascularization in IGT subjects during the post-trial 10-year period.