Antidiabetics

Antidiabetics: Uses, Side Effects, List, Safety

Antidiabetic Drugs are medications used to treat diabetes mellitus by altering the glucose level in the blood. With the exceptions of insulin, exenatide, liraglutide and pramlintide, all are administered orally and are thus also called oral hypoglycemic agents or oral antihyperglycemic agents. There are different classes of anti-diabetic drugs, and their selection depends on the nature of the diabetes, age and situation of the person, as well as other factors.

Diabetics prevalence worldwide 2019 and 2045. Around 9.3 percent of the global adult population suffered from diabetes in 2019 – by the year 2045 this number is expected to rise to almost 11 percent. Diabetes, or diabetes mellitus, refers to a group of metabolic disorders that result in chronic high blood sugar levels.

How does antidiabetic drugs work?

Currently, six classes of oral antidiabetic drugs (OADs) are available: biguanides (e.g., metformin), sulfonylureas (e.g., glimepiride), meglitinides (e.g., repaglinide), thiazolidinediones (e.g., pioglitazone), dipeptidyl peptidase IV inhibitors (e.g., sitagliptin), and α-glucosidase inhibitors (e.g., acarbose). The sulfonylureas, for example, stimulate the insulin-secreting beta cells of the pancreas to produce more insulin. With long-term use, this effect appears to diminish, but plasma glucose levels remain low. The most serious adverse effect of these drugs, which occurs only rarely, is profound hypoglycemia; in severe cases this can result in coma.

Repaglinide and nateglinide, which belong to a class of chemicals known as meglitinides, are other orally active compounds that stimulate insulin release from the pancreas. These agents work by closing potassium channels on the surface of beta cells, which causes an influx of calcium ions into the cells and a consequent outflow of insulin from cellular storage vesicles. The thiazolidinediones (e.g., pioglitazone, rosiglitazone) decrease insulin resistance. These oral hypoglycemic drugs exert their effects by activating so-called PPARγ (peroxisome proliferator-activated receptor-gamma) receptors, which are found primarily in adipose tissue; when activated, PPARγ prompts the transcription (synthesis of RNA from DNA) of genes that regulate glucose and lipid metabolism. Because hepatotoxicity is a major concern with thiazolidinediones, regular monitoring of liver metabolism is performed in individuals taking these drugs. Metformin, an oral antihyperglycemic drug that belongs to the biguanide class of agents, lowers glucose levels by decreasing liver production of glucose and increasing the action of insulin in fat and muscle. Chemicals in metformin medications, however, have been linked to dangerous side effects, including a possible increase in cancer risk.

Other antidiabetic drugs include pramlintide and exenatide. Pramlintide is an injectable synthetic hormone (based on the human hormone amylin) that regulates blood glucose levels by slowing the absorption of food in the stomach and by inhibiting glucagon, which normally stimulates liver glucose production. Exenatide is an injectable antihyperglycemic drug that works similarly to incretins, or gastrointestinal hormones, such as gastric inhibitory polypeptide, that stimulate insulin release from the pancreas. Exenatide has a longer duration of action than incretins produced by the body because it is less susceptible to degradation by an enzyme called dipeptidyl peptidase-4 (DPP-4). A drug called sitagliptin specifically inhibits DPP-4, thereby increasing levels of naturally produced incretins. Side effects associated with these drugs are often mild, although pramlintide can cause profound hypoglycemia in patients with type I diabetes.

Safety of Antidiabetics

Diabetes medications are not frequently associated with serious adverse events or major drug interactions. But that doesn’t mean there aren’t concerns to be addressed when treating diabetic patients to help ensure safe and effective therapies.

Probably the biggest concern with drug interactions or adverse events in diabetic patients is the potential for loss of glucose control (hypoglycemia/hyperglycemia). Hypoglycemia is a potentially serious concern in diabetic patients, especially those receiving multiple antidiabetic agents. Patients receiving insulin or insulin secretagogues (e.g., sulfonylureas, meglitinides) are at greatest risk.

Close glucose monitoring is essential in preventing loss of glucose control. Dosage adjustments of antidiabetic therapy may be necessary during concurrent use with the following drugs:

Hypoglycemia risk:

  • Insulin or insulin secretagogues (e.g., sulfonylureas, meglitinides)
  • Mecasermin
  • Quinine
  • Sulfamethoxazole/trimethoprim
  • Sunitinib
  • Somatostatin analogues

Hyperglycemia risk:

  • Antipsychotics
  • Corticosteroids
  • Diuretics
  • Estrogens
  • Protease inhibitors
  • Somatostatin analogues

In addition, Sulfonylureas can cause many harmful side effects, such as low blood sugar and heart problems. After years of uncertainty, there is growing evidence that patients taking sulfonylureas are more likely to have a heart attack or die from heart issues than other diabetes patients on metformin alone. Some types of sulfonylureas have more side effects than others, however For example, patients taking Diabeta are more likely to die than patients taking other sulfonylureas. 

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