Amaryl

Amaryl is an oral hypoglycemic drug which lowers blood glucose level effectively. It works by stimulating insulin release from the beta cells of the pancreas and may slightly improve insulin resistance in peripheral target tissues like muscle and fat. 

It is a third-generation sulfonylurea that reduces fasting plasma glucose (FPG) concentrations by 60 to 70 mg per dL (3.3-3.9 mmol/L). Hypoglycemia is the most worrisome side-effect of sulfonylureas. But newer drugs like glimepiride are associated with a lower incidence of hypoglycemia. 

This drug is well absorbed orally, and is 90% or more bound to plasma proteins. Glimepiride is primarily metabolized in the liver and the metabolites (active/inactive) are excreted in urine. As such, it should be used cautiously in patients with liver or kidney dysfunction. 

Its significant action is to lower blood glucose level in normal subjects, and in type 2 diabetics, but not in type 1 diabetics. Being more potent and clinically superior, only the second or third generation sulfonylureas (e.g. glimepiride) are employed now.

Amaryl is the drug which is commonly prescribed by the doctors in those who are diabetic but not obese.

It acts in the following ways in order to maintain the blood sugar levels:

• It increases pancreatic beta-cell sensitivity  to glucose and thus promotes enhanced insulin release 
• Improves tissue sensitivity to insulin
• Reduces peripheral resistance to insulin action

It provokes a brisk release of insulin from pancreas. The rate of insulin secretion at any glucose concentration is increased, i.e. insulin release is provoked even at low-glucose concentration risking production of severe and unpredictable hypoglycemia. 

In type 2 DM, the kinetics of insulin release in response to glucose or meals is delayed and subdued. Glimepiride primarily augments the 2nd phase insulin secretion with little effect on the 1st phase. 

After few months of administration, the insulinaemic action of glimepiride declines, probably due to down regulation of sulfonylurea receptors on beta cells, but improvement in glucose tolerance is maintained. 

In this phase, they sensitize the target tissues (especially liver) to the action of insulin. This is due to increase in number of insulin receptors and/or a post-receptor action improving translation of receptor activation. 

It is hypothesized that long-term improvement in carbohydrate tolerance leads to overall lowering of circulating insulin concentration which reverses the down regulation of insulin receptors. An apparent increase in their number occurs. Moreover, it increases insulin receptors on target cells and inhibits gluconeogenesis in the liver.

As well as stimulating insulin production, glimepiride may cause a mild reduction in insulin resistance and may be less likely to cause low blood sugars than other sulfonylureas. 

Some important matters you should know before starting this drug therapy are: 

• Once daily dose as monotherapy or in combination with insulin.
• Glimepiride dose is lowest dose of any sulfonylurea compound.
• It has a long duration of action with a half-life of four hours.
• Glimepiride is associated with a lower incidence of hypoglycemia.
• Safe for people who have advanced kidney disease indicated by an elevated creatinine level. Other sulfonylureas are  usually not recommended when the creatinine level is elevated.
• Glimepiride also does not block the normal relaxation of blood vessels and does not affect coronary arteries. These unwanted side effects may occur infrequently with other sulfonylureas.

Amaryl is preferably indicated in Type 2 diabetes mellitus except in overweight diabetics. The drug should be started with 1-2 mg daily. 

It may be increased in increments of 1-2 mg at intervals of 1-2 weeks. Maintenance dose should not exceed 4 mg daily.

Safety of glimepiride during pregnancy is not established. Change over to insulin is advised. Glimepiride is secreted in milk, that’s why it should not be given to nursing mothers.

Use of glimepiride is restriced in certain medical conditions such as Type 1 diabetes mellitus, pregnancy, postoperative patient, severe renal insufficiency and hepatic failure, elderly patient with impaired renal function, young ketotic patients etc.

All sulfonylureas including Amaryl have been associated with weight gain and thus, may not be the optimal first choice for obese patients. 

Hypoglycemia is the most alarming side-effect which may occur in those diabetics who are receiving glimepiride. In order to avoid hypoglycemia, you should start this drug at low dose and titrate upwards slowly. Additionally, meals should not be missed.

There are some limitations of glimepiride as hypoglycemic agent:

• The drug is ineffective in diabetic patients who have no endogenous insulin.
• At least 30% of beta-cells must be in active condition for the action of Sulfonylureas.
• Continued dietary restrictions are essential to maximize the efficacy of the Sulfonylureas.
• Cannot be used in diabetic complications.
• Contraindicated in patient with hepatic and renal failure, Type-1 diabetes, pregnancy and lactation.

There are also some drug interactions when glimepiride is used with some other drugs simultaneously. Drugs that enhance glimepiride action (may precipitate hypoglycaemia) are given below:

• Phenylbutazone, sulfinpyrazone, salicylates and sulfonamides displace glimepiride from protein binding sites.
• Cimetidine, ketoconazole, sulfonamides and warfarin inhibit its metabolism or excretion.
• Chloramphenicol and acute alcohol intake synergise by causing hypoglycaemia.
• Salicylates, propranolol (cardioselective beta-1 blockers are less liable), sympatholytic antihypertensives, lithium and theophylline synergise with or prolong pharmacodynamic action.

On the contrary, drugs that decrease glimepiride action (vitiate diabetes control) are:

• Phenobarbitone, phenytoin, rifampicin and chronic alcoholism induce glimepiride metabolism.
• Corticosteroids, thiazides, furosemide, and oral contraceptives antagonize its action or suppress insulin release.

If you notice any side effects of Amaryl, immediately make an appointment with your doctor.Incidence of adverse effects is quite low (3-7%).

• Hypoglycemia: It is the commonest problem, may occasionally be severe and rarely fatal. It is more common in elderly, liver and kidney disease patients and when potentiating drugs are added. Treatment of hypoglycemic episode is to give glucose, may be for a few days because hypoglycemia may occur.

• Hypersensitivity: Rashes, photosensitivity, purpura, transient leukopenia, rarely agranulocytosis. Flushing and a disulfiram-like reaction after alcohol are reported to occur in some individuals taking glimepiride.

• Nonspecific side effects: Majority of diabetics started on SUs tend to gain 1-3 kg weight. This may be a consequence of their insulinaemic action. Nausea, vomiting, flatulence, diarrhea or constipation, headache and paresthesias are generally mild and infrequent.