Glinate

Uses

Glinate is used for an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.

Glinate is also used to associated treatment for these conditions: Type 2 Diabetes Mellitus

How Glinate works

Glinate activity is dependent on the presence functioning β cells and glucose. In contrast to sulfonylurea insulin secretatogogues, nateglinide has no effect on insulin release in the absence of glucose. Rather, it potentiates the effect of extracellular glucose on ATP-sensitive potassium channel and has little effect on insulin levels between meals and overnight. As such, nateglinide is more effective at reducing postprandial blood glucose levels than fasting blood glucose levels and requires a longer duration of therapy (approximately one month) before decreases in fasting blood glucose are observed. The insulinotropic effects of nateglinide are highest at intermediate glucose levels (3 to 10 mmol/L) and it does not increase insulin release already stimulated by high glucose concentrations (greater than 15 mmol/L). Glinate appears to be selective for pancreatic β cells and does not appear to affect skeletal or cardiac muscle or thyroid tissue.

Dosage

Glinate dosage

Initial dose: 120 mg orally 3 times a day before meals

Maintenance dose: 60 to 120 mg orally 3 times a day before meals

For patients who are near goal HbA1c when therapy is initiated, therapy should be initiated at 60 mg orally 3 times. May be used as monotherapy, or in combination with metformin or a thiazolidinedione. As an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.

Take orally 1 to 30 minutes before a meal. Patients who skip a meal should be instructed to skip the dose for that meal

Side Effects

Hypoglycaemia, upper respiratory tract infection, back pain, flu-like symptoms, dizziness, arthropathy, diarrhoea, accidental trauma, bronchitis, cough.

Toxicity

An overdose may result in an exaggerated glucose-lowering effect with the development of hypoglycemic symptoms.

Precaution

Patient with adrenal and/or pituitary impairment. Severe renal and moderate to severe hepatic impairment. Pregnancy and lactation.

Interaction

CYP2C9 and CYP3A4 inhibitors or inducers may alter metabolism of nateglinide. Increased hypoglycaemic effects with MAOIs, nonselective β-adrenergic blockers, NSAIDs, salicylates. Decreased hypoglycaemic effects with corticosteroids, sympathomimetic agents, thiazide diuretics, thyroid hormones.

Food Interaction

• Take with food. Take up to 30 minutes before meals.

[Moderate] GENERALLY AVOID: Alcohol may cause hypoglycemia or hyperglycemia in patients with diabetes.

Hypoglycemia most frequently occurs during acute consumption of alcohol.

Even modest amounts can lower blood sugar significantly, especially when the alcohol is ingested on an empty stomach or following exercise.

The mechanism involves inhibition of both gluconeogenesis as well as the counter-regulatory response to hypoglycemia.

Episodes of hypoglycemia may last for 8 to 12 hours after ethanol ingestion.

By contrast, chronic alcohol abuse can cause impaired glucose tolerance and hyperglycemia.

Moderate alcohol consumption generally does not affect blood glucose levels in patients with well controlled diabetes.

A disulfiram-like reaction (e.g., flushing, headache, and nausea) to alcohol has been reported frequently with the use of chlorpropamide and very rarely with other sulfonylureas.

MANAGEMENT: Patients with diabetes should avoid consuming alcohol if their blood glucose is not well controlled, or if they have hypertriglyceridemia, neuropathy, or pancreatitis.

Patients with well controlled diabetes should limit their alcohol intake to one drink daily for women and two drinks daily for men (1 drink = 5 oz wine, 12 oz beer, or 1.5 oz distilled spirits) in conjunction with their normal meal plan.

Alcohol should not be consumed on an empty stomach or following exercise.

Glinate Drug Interaction

Moderate: aspirin, aspirin, sitagliptin, metoprolol, metoprolol, levothyroxine, linagliptin, liraglutideUnknown: rosuvastatin, omega-3 polyunsaturated fatty acids, insulin glargine, insulin glargine, atorvastatin, pregabalin, esomeprazole, clopidogrel, cyanocobalamin, ascorbic acid, ergocalciferol, cholecalciferol

Glinate Disease Interaction

Major: type I diabetes, cardiovascular riskModerate: hypoglycemia, liver disease

Volume of Distribution

10 liters in healthy subjects

Elimination Route

Rapidly absorbed following oral administration prior to a meal, absolute bioavailability is estimated to be approximately 73%. Peak plasma concentrations generally occur within 1 hour of oral administration. Onset of action is <20 minutes and the duration of action is approximately 4 hours.

Half Life

1.5 hours

Elimination Route

Urine (83%) and feces (10%)

Pregnancy & Breastfeeding use

Pregnancy Category C. Either studies in animals have revealed adverse effects on the foetus (teratogenic or embryocidal or other) and there are no controlled studies in women or studies in women and animals are not available. Drugs should be given only if the potential benefit justifies the potential risk to the foetus.

Contraindication

IDDM, diabetic ketoacidosis.

Special Warning

Renal Dose Adjustments: No adjustment recommended

Mild hepatic impairment: No adjustment recommended

Moderate to severe hepatic impairment: Use caution

Elderly: No adjustment recommended; however, some individuals may have a greater sensitivity to therapy. Insulin therapy may be temporarily needed in times of fever, infection, trauma, or surgery.

Younger than 18 years: Safety and efficacy have not been established in patients younger than 18 years.

Acute Overdose

Symptoms: Hypoglycaemia.

Management: Use IV glucose in severe reaction.

Storage Condition

Store at 25° C.

Innovators Monograph

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