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What is the Difference Between Sulfonylureas and Meglitinides

September 24, 2023 Posted by Dr Neelaka M

The key difference between Sulfonylureas and Meglitinides is that Sulfonylureas have a slower onset and longer duration of action, making them more effective for controlling blood sugar levels throughout the day, while Meglitinides have a faster onset and shorter duration of action, making them particularly well-suited when blood sugar levels are typically rising.

Sulfonylureas and meglitinides are two classes of oral medications used to treat type 2 diabetes. They work by stimulating the pancreas to release insulin, lowering blood sugar levels. Sulfonylureas are older medications that have been used for many years to treat type 2 diabetes. They are generally safe and effective but can cause side effects such as hypoglycemia, weight gain, and gastrointestinal problems. Meglitinides are newer medications similar in action to sulfonylureas, but they have a faster onset with a shorter duration of action. This makes them particularly well-suited to use before meals. Meglitinides are also less likely to cause hypoglycemia and weight gain than sulfonylureas. Altogether, meglitinides may be a better choice for people with a high risk of hypoglycemia or weight gain, while sulfonylureas may be a better choice for people who need to control their blood sugar levels throughout the day.

CONTENTS

1. Overview and Key Difference
2. What are Sulfonylureas 
3. What are Meglitinides
4. Similarities – Sulfonylureas and Meglitinides
5. Sulfonylureas vs. Meglitinides in Tabular Form
6. Summary – Sulfonylureas vs Meglitinides

What are Sulfonylureas?

Sulfonylureas are hypoglycemic drugs that contain phenyl sulfonyl urea and are considered the oldest oral anti-diabetic medications. It is widely used to treat patients with type 2 diabetes mellitus as a monotherapy or combined treatment with other oral or injectable anti-diabetic drugs. Sulfonylureas is widely used as an add-on to metformin. First-generation Sulfonylureas include tolbutamide, and second-generation Sulfonylureas include glipizide and glimepiride. Sulfonylureas inhibit the ATP-sensitive K channels of the pancreatic beta cells to stimulate insulin secretion. The increased insulin secretion is independent of the blood glucose level. Therefore, hypoglycemia is the most common side effect associated with Sulfonylureas. Patients with hypoglycemia may experience sweating, irritability, confusion, shakiness, and hunger.

Sulfonylureas and Meglitinides - Side by Side Comparison

Figure 01: Chemical Structure of Sulfonylureas

In addition, the reduced glucose level is also related to decreased glucose metabolism in the liver, decreased glucagon secretion, and increased glucose sensitivity to insulin. Sulfonylureas are typically initiated at a low oral dose and gradually increased based on glycemic control. It is the least suitable anti-diabetic drug for patients with lower glomerular filtration rates. It is circulated through the body by binding with high-affinity plasma proteins. The most common side effects of Sulfonylureas include weight gain; therefore, it is not recommended for obese patients. In addition, Sulfonylureas is also not recommended for pregnant and lactating patients.

What are Meglitinides?

Meglitinides are a class of anti-diabetic medications used to treat type 2 diabetes with a similar action to Sulfonylureas. They bind to ATP-sensitive potassium channels of pancreatic beta cells with a high affinity and stimulate insulin secretion. Meglitinides do not internalize during the action, offering a rapid onset of action. According to studies, Meglitinides do not stimulate insulin secretion in vitro or fasted animal models. This suggests that Meglitinides-stimulated insulin secretion depends on the plasma glucose concentration. There are two Meglitinides, Repaglinide and Nateglinide, available in the market.

Sulfonylureas vs Meglitinides in Tabular Form

Figure 02: Chemical Structure of Meglitinides

Repaglinide is a carbamoylmethyl benzoic acid derivative, while Nateglinide is a phenylalanine derivative. Both these act more quickly than Sulfonylureas. Meglitinides are rapidly absorbed and metabolized in the liver before excreting in feces with an elimination half-life of 30 minutes. The most frequent side effect of Meglitinides is hypoglycemia. However, serious incidents of hypoglycemia are not common; the overall incidents are similar to the Sulfonylureas.

What are the Similarities Between Sulfonylureas and Meglitinides?

  • Sulfonylureas and Meglitinides work by binding to and closing potassium channels in pancreatic beta cells to release insulin.
  • Both medications effectively lower blood sugar levels in people with type 2 diabetes.
  • They can cause side effects such as hypoglycemia (low blood sugar), weight gain, and gastrointestinal problems.
  • They are not recommended for people with type 1 diabetes, severe liver disease, or severe kidney disease.

What is the Difference Between Sulfonylureas and Meglitinides?

Sulfonylureas and meglitinides are prescribed to treat type 2 diabetes by stimulating insulin release and lowering blood sugar. Both work by binding to ATP-dependent K channels of the pancreatic beta cells to secrete insulin. However, there is a distinct difference between Sulfonylureas and Meglitinides. Sulfonylureas have a slower onset and longer duration of action, making them more effective for controlling blood sugar levels throughout the day. In contrast, Meglitinides have a faster onset and shorter duration of action, making them particularly well-suited when blood sugar levels are typically rising. Sulfonylureas-stimulated insulin secretion is independent of the blood glucose level, while Meglitinide-stimulated insulin secretion depends on the plasma glucose concentration. Compared to Meglitinides, Sulfonylureas have a higher risk of causing hypoglycemia and weight gain.

Below is a summary of the difference between Sulfonylureas and Meglitinides in tabular form for side-by-side comparison.

Summary – Sulfonylureas vs. Meglitinides

Sulfonylureas and Meglitinides are two classes of oral medications used to treat type 2 diabetes. They work by stimulating insulin release from pancreatic beta cells with several differences. Sulfonylureas have a slower onset and longer duration of action, making them suitable for all-day blood sugar control, while Meglitinides have a faster onset and shorter duration, ideal for when blood sugar levels typically rise, especially before meals. Sulfonylureas can cause hypoglycemia and weight gain, while Meglitinides carry a lower risk of these side effects. Additionally, Sulfonylureas may not be suitable for obese or pregnant individuals, while Meglitinides, including Repaglinide and Nateglinide, offer quicker metabolism and elimination. Thus, this is the summary of the difference between Sulfonylureas and Meglitinides. Both drug classes should be used cautiously, considering their distinct characteristics, in treating type 2 diabetes.

Reference:

1. Furman, Brian L. “Meglitinide.” xPharm: The Comprehensive Pharmacology Reference, 2007, pp. 1–2.
2. Furman, Brian L. “Sulfonylureas.” xPharm: The Comprehensive Pharmacology Reference, 2007, pp. 1–2.

Image Courtesy:

1. “Sulfonylurea group and radicals” By Fvasconcellos (talk · contribs) – Own work (Public Domain) via Commons Wikimedia
2. “Meglitinide Structure” By JoeyChen – Own work (CC BY-SA 4.0) via Commons Wikimedia

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Filed Under: Nutrients & Drugs

About the Author: Dr Neelaka M

Dr. Neelaka Molagoda is a dedicated Drug Development and Pharmaceutical Biotechnology Lecturer, who earned his PhD in Life Sciences from Jeju National University, focusing on the pharmaceutical potential of the dietary flavonoid fisetin. His exceptional research earned him the Dean's Award for Excellent PhD Research. He has extensive experience in mammalian cell culture, zebrafish handling, bacterial transformation, siRNA-mediated gene silencing, PCR, western blot analysis, flow cytometry, enzyme activity assays, and confocal microscopy. His research delves into the mechanisms of drug action in nutraceuticals, with a focus on anti-inflammatory, anti-oxidative, anti-cancer, anti-melanogenic, and anti-angiogenic activities, as well as their effect on osteoblast differentiation and growth promotion.
Dr. Molagoda is a skilled and passionate researcher committed to advancing innovative treatments for various diseases.

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