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What are Insulin Secretagogues? Types, Benefits and Side Effects

What are Insulin Secretagogues? Types, Benefits and Side Effects

Insulin secretagogues (otherwise known as insulin-releasing drugs) are diabetes medications indicated for the treatment of type II diabetes. In diabetes patients, there is often insufficient insulin production. Synthesized by beta cells of the islets of Langerhans, insulin is a type of hormone that plays an important role in blood glucose regulation. Through the stimulation of insulin synthesis, insulin secretagogues helps reduce the amount of excess sugar in the blood and thereby restores the blood glucose level.  At the same time, insulin secretagogues are able to promote the release of insulin from the pancreas to manage hyperglycemia. Insulin secretagogues are especially useful for patients who are unable to achieve satisfactory glycemic control with lifestyle modification, such as exercise and diet change, alone. They are also ideal for patients who are unresponsive to other diabetes medications.

What types of insulin secretagogues are available?

There are several types of insulin secretagogues, including meglitinides (nateglinide, repaglinide) and sulfonylureas (glyburide, glipizide, glimepiride, and chlorpropamide). In addition, there is a type of insulin secretagogues called D-phenylalanine derivatives. Sulfonylureas are designed for once-daily or twice-daily usage. Depending on the brand, they can be used in the morning or at night. The recommended dose varies greatly among different types of sulfonylureas. For example, the usual dose for glimepiride ranges from 1mg to 4mg, while the recommended dose for glipizide is 5mg to 40mg. The daily dose for chlorpropamide is around 100mg to 500mg, while glyburide is commonly prescribed with a daily dose of 1.25mg to 20mg. The recommended dose range for nateglinide is 60mg to 120mg, while the usual dose of Repaglinide ranges from 0.5mg to 4mg. Also, meglitinides are intended to be used 15 to 30 minutes prior to meals.

While sharing the same mechanism of action, insulin secretagogues vary substantially in terms of their pharmacologic actions. Some insulin secretagogues have a rapid onset of action but a shorter duration of effect, while others have a slow onset of action but a longer duration of action. Sulfonylureas are specially formulated to promote the pancreatic release of insulin over several hours, while meglitinides are able to provide a short-term insulin burst after a meal.

What benefits do insulin secretagogues have?

Having insulin-releasing properties, insulin secretagogues effectively reduce elevated blood sugar level for better glycemic control. Sulfonylureas are especially effective in blood sugar control.

Affordable yet effective, insulin secretagogues have a good side effect profile and are mostly well tolerated. They are not likely to cause severe adverse effects if used correctly. Most insulin secretagogues have been approved by the FDA and have been clinically proven as safe and effective. Formulated as oral tablets, insulin secretagogues are ideal for patients who are averse to injections.

What side effects can insulin secretagogues cause?

As with most anti-hyperglycemic agents, insulin secretagogues could cause hypoglycemia, a condition characterized by excessively low blood glucose. Elderly patients and patients with cardiovascular diseases are particularly susceptible to the effects of hypoglycemia. However, there are ways to reverse the effects of hypoglycemia. When hypoglycemic symptoms occur, patients should take 15g to 20g of simple carbohydrates or glucose.

Apart from hypoglycemia, the use of insulin secretagogues may also result in weight gain. This may subsequently lead to other complications such as circulatory problems. Plus, some insulin secretagogues, such as sulfonylureas, may lose their efficacy over time. Due to their unique mode of action, sulfonylureas work best when diabetes is first diagnosed, which is when beta cell function is at its greatest. This is why sulfonylureas should be used cautiously and judiciously. In most cases, sulfonylureas will lose their efficacy in one or two years. To prevent sulfonylureas from losing their effectiveness, it is recommended to use them in combination with other hypoglycemic agents that have a different mode of action.

Choosing the right diabetes medication 

Patients should consult their doctor in order to select the most appropriate diabetes drug. While generally safe and effective, insulin secretagogues may not be suitable for everyone. For example, patients who have worsening kidney functions should avoid using insulin secretagogues (or have the dosage reduced). With the exception of glyburide, most insulin secretagogues are categorized as Category C drugs, which should not be used during pregnancy. Being a Category B drug, the effects of glyburide in pregnant women are not well studied, although findings from animal studies suggest that it is safe for use. As a rule of thumb, insulin secretagogues should be used cautiously in pregnant patients. In particular, insulin secretagogues that belong to Category C should be avoided entirely during pregnancy, unless the potential benefits outweigh the harm.

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