Pharmacology of type 2 diabetes Flashcards
List the drugs available to treat Type 2 diabetes mellitus (NIDDM)
Metformin: Metformin is a biguanide drug that works by decreasing the amount of glucose produced by the liver and improving insulin sensitivity. It is usually taken orally and is often the first-line therapy for type 2 diabetes.
Sulfonylureas: Sulfonylureas are a class of drugs that stimulate the pancreas to produce more insulin. Examples include glyburide, glipizide, and glimepiride.
DPP-4 inhibitors: DPP-4 inhibitors are a class of drugs that increase the levels of incretin hormones, which stimulate the pancreas to produce more insulin and decrease the amount of glucose produced by the liver. Examples include sitagliptin, saxagliptin, and linagliptin.
GLP-1 receptor agonists: GLP-1 receptor agonists are a class of drugs that mimic the action of incretin hormones and stimulate the pancreas to produce more insulin. They also slow down gastric emptying and promote satiety, which can lead to weight loss. Examples include exenatide, liraglutide, and dulaglutide.
SGLT2 inhibitors: SGLT2 inhibitors are a class of drugs that prevent the kidneys from reabsorbing glucose, leading to increased urinary excretion of glucose and lower blood glucose levels. Examples include canagliflozin, dapagliflozin, and empagliflozin.
Insulin: Insulin is a hormone that lowers blood glucose levels by promoting the uptake and storage of glucose in the liver, muscle, and fat cells. Insulin therapy may be required for people with advanced type 2 diabetes who cannot achieve adequate glucose control with oral medications alone.
Describe the mechanisms of action of these drugs
Metformin: Metformin works by reducing the amount of glucose produced by the liver and improving insulin sensitivity. It does this by activating AMP-activated protein kinase (AMPK), which leads to increased glucose uptake and decreased glucose production in the liver.
Sulfonylureas: Sulfonylureas work by stimulating the pancreas to produce more insulin. They bind to the ATP-sensitive potassium channels on the beta cells of the pancreas, causing depolarization and calcium influx, which triggers insulin release.
DPP-4 inhibitors: DPP-4 inhibitors work by blocking the enzyme dipeptidyl peptidase-4 (DPP-4), which breaks down incretin hormones such as GLP-1 and GIP. By increasing the levels of these hormones, DPP-4 inhibitors stimulate insulin secretion and decrease glucagon production, leading to lower blood glucose levels.
GLP-1 receptor agonists: GLP-1 receptor agonists work by mimicking the action of GLP-1, a hormone that is secreted by the gut in response to food intake. GLP-1 receptor agonists stimulate insulin secretion, decrease glucagon production, slow down gastric emptying, and promote satiety, which can lead to weight loss.
SGLT2 inhibitors: SGLT2 inhibitors work by inhibiting the sodium-glucose cotransporter 2 (SGLT2) in the kidneys, which is responsible for reabsorbing glucose from the urine back into the bloodstream. By blocking SGLT2, these drugs increase urinary excretion of glucose, leading to lower blood glucose levels.
Insulin: Insulin lowers blood glucose levels by promoting the uptake and storage of glucose in the liver, muscle, and fat cells. It binds to insulin receptors on the surface of these cells, triggering a signaling cascade that leads to the insertion of glucose transporters (GLUT4) into the cell membrane and glucose uptake into the cell. Insulin also inhibits glucose production in the liver and promotes glycogen synthesis and storage.
Describe the major side-effects associated with each class of drug
Metformin: Metformin is generally well-tolerated, but common side effects include gastrointestinal symptoms such as nausea, vomiting, diarrhea, and abdominal discomfort. These symptoms can usually be minimized by taking the medication with food and starting with a low dose that is gradually increased.
Sulfonylureas: Sulfonylureas can cause hypoglycemia (low blood sugar) as a side effect, especially if the dose is too high or if the person skips a meal or engages in intense physical activity. Other side effects may include weight gain, gastrointestinal symptoms, and skin rash.
DPP-4 inhibitors: DPP-4 inhibitors are generally well-tolerated, but common side effects include headache, nasopharyngitis (common cold), and gastrointestinal symptoms. They may also increase the risk of pancreatitis (inflammation of the pancreas) and joint pain.
GLP-1 receptor agonists: GLP-1 receptor agonists can cause gastrointestinal symptoms such as nausea, vomiting, diarrhea, and constipation. They may also increase the risk of pancreatitis and thyroid cancer, although the absolute risk is low. In some cases, they may also cause injection site reactions and hypersensitivity reactions.
SGLT2 inhibitors: SGLT2 inhibitors can cause genital mycotic infections (fungal infections of the genital area), urinary tract infections, and increased urination. They may also increase the risk of ketoacidosis (a potentially life-threatening condition characterized by high levels of ketones in the blood) and bone fractures. In rare cases, they may cause allergic reactions and kidney injury.
Insulin: Insulin can cause hypoglycemia as a side effect, especially if the dose is too high or if the person skips a meal or engages in intense physical activity. Other side effects may include weight gain, injection site reactions, and allergic reactions. Long-term use of insulin may also increase the risk of retinopathy (eye damage), neuropathy (nerve damage), and cardiovascular disease.
Appreciate the role of the incretin system in enhancing insulin release
The incretin system refers to the hormones and signaling pathways that regulate insulin secretion in response to nutrient ingestion. The two primary incretin hormones are glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP).
GLP-1 and GIP are secreted by the intestine in response to food ingestion, and they stimulate insulin release from the pancreatic beta cells in a glucose-dependent manner. This means that the incretin hormones only enhance insulin secretion when glucose levels are elevated, such as after a meal.
GLP-1 and GIP also have other beneficial effects on glucose metabolism, such as promoting beta cell growth and survival, suppressing glucagon secretion (which raises blood glucose levels), and slowing gastric emptying, which helps to prevent large spikes in blood glucose levels after a meal.
There are drugs called incretin mimetics, which are designed to mimic the actions of GLP-1 in the body, that are used to treat type 2 diabetes. These drugs stimulate insulin secretion and improve glucose control, while also promoting weight loss and reducing the risk of cardiovascular disease.
Appreciate the need to develop new approaches to tackling obesity to prevent the development of diabetes mellitus
Obesity is a major risk factor for the development of type 2 diabetes mellitus. This is because excess body fat can lead to insulin resistance, which means that the body’s cells become less responsive to the effects of insulin, leading to high blood glucose levels.
Current approaches to tackling obesity and preventing diabetes include lifestyle modifications, such as diet and exercise, and medications that can aid in weight loss or improve insulin sensitivity. However, these approaches are often limited in their effectiveness and may not be suitable or sustainable for all individuals.
There is a need to develop new and innovative approaches to tackling obesity and preventing diabetes. One area of research is focused on developing drugs that target the molecular pathways that regulate appetite and metabolism. For example, there are drugs in development that mimic the effects of certain gut hormones, such as GLP-1 and GIP, that can promote weight loss and improve glucose control.
Another area of research is focused on the microbiome, which is the collection of microorganisms that inhabit the human gut. There is growing evidence that the microbiome plays a role in regulating appetite and metabolism, and that alterations in the microbiome may contribute to obesity and diabetes. Developing interventions that target the microbiome, such as probiotics or fecal microbiota transplantation, may be a promising avenue for preventing diabetes in individuals who are overweight or obese.
