Meglitinides or glinides are a class of drugs used to treat

type 2 diabetes Type 2 diabetes (T2D), formerly known as adult-onset diabetes, is a form of diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. Common symptoms include increased thirst, frequent ...

Drugs

Repaglinide (trade name Prandin) gained US

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respo ...

approval in 1997. Other drugs in this class include nateglinide (Starlix) and mitiglinide (Glufast).

Side effects

Side effects include weight gain and

hypoglycemia Hypoglycemia (American English), also spelled hypoglycaemia or hypoglycæmia (British English), sometimes called low blood sugar, is a fall in blood sugar to levels below normal, typically below 70 mg/dL (3.9 mmol/L). Whipple's tria ...

. While the potential for hypoglycemia is less than for those on

sulfonylurea Sulfonylureas or sulphonylureas are a class of organic compounds used in medicine and agriculture. The functional group consists of a sulfonyl group (-S(=O)2) with its sulphur atom bonded to a nitrogen atom of a ureylene group (N,N-dehydrourea ...

s, it is still a serious potential side effect that can be life-threatening. Patients on this medication should know the signs and symptoms of hypoglycemia and appropriate management. Repaglinide caused an increased incidence in male rats of benign adenomas (tumors) of the thyroid and liver.Prandin (repaglinide) prescribing information
fda.gov No such effect was seen with another drug of this class, nateglinide.Starlix (nateglinide) prescribing information
fda.gov A 2020 Cochrane systematic review did not find enough evidence of reduction of all-cause mortality, serious adverse events, cardiovascular mortality, non-fatal

myocardial infarction A myocardial infarction (MI), commonly known as a heart attack, occurs when Ischemia, blood flow decreases or stops in one of the coronary arteries of the heart, causing infarction (tissue death) to the heart muscle. The most common symptom ...

, non-fatal

stroke Stroke is a medical condition in which poor cerebral circulation, blood flow to a part of the brain causes cell death. There are two main types of stroke: brain ischemia, ischemic, due to lack of blood flow, and intracranial hemorrhage, hemor ...

or end-stage renal disease when comparing

metformin Metformin, sold under the brand name Glucophage, among others, is the main first-line medication for the treatment of type2 diabetes, particularly in people who are overweight. It is also used in the treatment of polycystic ovary syndrome, ...

monotherapy to meglitinide for the treatment of type 2 diabetes.

Mechanism of action

They bind to an ATP-dependent K⁺ (K_ATP) channel on the cell membrane of pancreatic

beta cell Beta cells (β-cells) are specialized endocrine cells located within the pancreatic islets of Langerhans responsible for the production and release of insulin and amylin. Constituting ~50–70% of cells in human islets, beta cells play a vi ...

s in a similar manner to

s but have a weaker binding affinity and faster dissociation from the SUR1 binding site. This increases the concentration of intracellular potassium, which causes the electric potential toward the intracellular side of the membrane to become more positive. This

depolarization In biology, depolarization or hypopolarization is a change within a cell (biology), cell, during which the cell undergoes a shift in electric charge distribution, resulting in less negative charge inside the cell compared to the outside. Depolar ...

opens voltage-gated Ca²⁺ channels. The rise in intracellular calcium leads to increased fusion of

insulin Insulin (, from Latin ''insula'', 'island') is a peptide hormone produced by beta cells of the pancreatic islets encoded in humans by the insulin (''INS)'' gene. It is the main Anabolism, anabolic hormone of the body. It regulates the metabol ...

granula in the cell membrane, and therefore increased secretion of (pro) insulin.

References

Methoxy compounds Salicylamide ethers Benzoic acids Chloroarenes {{gastrointestinal-drug-stub