Oral Antidiabetic Drugs: Classes and Mechanisms

40 Questions

What is the primary advantage of metformin over insulin or sulfonylureas in treating hyperglycemia?

It is an insulin-sparing agent and does not increase weight or provoke hypoglycemia

What is the effect of metformin therapy on macrovascular disease?

It decreases the risk

What is the mechanism of action of thiazolidinediones (Tzds)?

Activation of peroxisome proliferator-activated receptor-gamma (PPAR-γ)

What is the effect of metformin on the absorption of vitamin B12?

It may interfere with the absorption

What is the primary action of thiazolidinediones (Tzds)?

Nuclear regulation of genes involved in glucose and lipid metabolism and adipocyte differentiation

What is the indication of metformin in combination with insulin secretagogues or thiazolidinediones?

Type 2 diabetes in whom oral monotherapy is inadequate

What is the effect of metformin on the prevention of type 2 diabetes?

It is efficacious in preventing the new onset of type 2 diabetes

What is the commonest unwanted effect of metformin?

Dose-related gastrointestinal disturbances

What is the underlying reason for secondary failure to sulfonylurea therapy in type 2 diabetes?

Progressive decrease in B-cell mass

Which of the following drugs can displace sulfonylureas from protein binding sites?

Salicylates

What is the mechanism of action of alpha glucosidase inhibitors like acarbose and miglitol?

Competitive inhibition of intestinal alpha glucosidase

What is the recommended timing of taking alpha glucosidase inhibitors like acarbose and miglitol?

Just prior to ingesting the first portion of a meal

What is a contraindication for the use of alpha glucosidase inhibitors like acarbose and miglitol?

Inflammatory bowel disease

What is a potential adverse effect of alpha glucosidase inhibitors like acarbose and miglitol when used with sulfonylureas?

Hypoglycemia

What is the effects of alpha glucosidase inhibitors like acarbose and miglitol on the absorption of starches and disaccharides?

Reduce the absorption of starches and disaccharides

What is the approved use of alpha glucosidase inhibitors like acarbose and miglitol?

In combination with sulfonylureas for type 2 diabetes

What is the effect of Acarbose on hepatic enzyme levels?

Reversible elevation

What is the primary function of GIP in the body?

Stimulating glucose-dependent insulin release

What is the effect of dipeptidyl peptidase-4 on incretins?

Rapidly degrades active incretins

What is the difference between GLP-1 and GIP in terms of their secretion site?

GLP-1 is secreted by the distal GI tract, while GIP is secreted by the proximal GI tract

What is the effect of Exenatide on insulin release?

Increases insulin release

What is the effect of Sitaglaptin on endogenous incretins?

Increases their activity by inhibiting dipeptidyl peptidase-4

What is the characteristic of GLP-1 in type 2 diabetes?

Levels are decreased

What is the difference between the insulinotropic response to GLP-1 and GIP in type 2 diabetes?

GIP response is diminished but not absent, while GLP-1 response is absent

What is the effect of PPAR-γ activation on insulin sensitivity in adipocytes, hepatocytes, and skeletal muscle?

Increased insulin sensitivity

Which of the following is a characteristic of thiazolidinediones?

Slow onset and offset of activity over weeks or months

What is the effect of pioglitazone on triglyceride levels compared to rosiglitazone?

More significant triglyceride-lowering effect

What is a common adverse effect of thiazolidinediones, especially when used with insulin or insulin secretagogues?

Fluid retention

Which of the following is a contraindication for thiazolidinedione use?

All of the above

What is the average weight gain associated with thiazolidinedione use?

1-3 kg

What is the effect of thiazolidinediones on HDL levels?

Increased HDL levels

What percentage of new users respond to thiazolidinedione therapy?

70%

What is the mechanism of action of metformin in reducing glucose absorption from the GIT?

Increased glucose to lactate conversion by enterocytes

What is the consequence of metformin's blockade of gluconeogenesis?

Impaired hepatic metabolism of lactic acid

Which of the following classes of oral antidiabetic drugs slow the absorption of starches?

Alpha-glucosidase inhibitors

What is the primary mechanism of action of biguanides in reducing hepatic glucose production?

Reduced gluconeogenesis and glycogenolysis

Which of the following drugs is not classified as an insulin secretagogue?

Metformin

What is the primary mechanism of action of thiazolidinediones in reducing glucose levels?

Increased glucose uptake by adipose tissues

What is the characteristic of metformin's excretion?

It is excreted by the kidneys as the active compound

What is the risk associated with metformin use in patients with renal insufficiency?

Increased risk of lactic acidosis

Study Notes

Classes of Oral Antidiabetic Drugs

Drugs that sensitize the body to insulin and/or control hepatic glucose production
- Biguanides (e.g., metformin)
  - Mechanism of action: direct stimulation of glycolysis, reduced hepatic and renal gluconeogenesis, slowing of glucose absorption from the GIT, and reduction of plasma glucagon levels
  - Metabolism and excretion: half-life of 1.5-3 hours, not bound to plasma proteins, not metabolized, and excreted by the kidneys as the active compound
  - Clinical use: first-line drug for the treatment of type II DM, decreases the risk of macrovascular and microvascular disease, and useful in preventing the new onset of type 2 diabetes
- Thiazolidinediones (Tzds) (e.g., pioglitazone and rosiglitazone)
  - Mechanism of action: activates peroxisome proliferator-activated receptor-gamma (PPAR-γ), decreases insulin resistance, and regulates genes involved in glucose and lipid metabolism
  - Clinical use: decreases the risk of macrovascular and microvascular disease, improves hyperglycemia, hypertriglyceridemia, and elevated HbA1c
  - Adverse effects: fluid retention, weight gain, and increased risk of heart failure
Drugs that stimulate the pancreas to make more insulin (Insulin secretagogues)
- Sulfonylureas
  - Mechanism of action: stimulates insulin release from pancreatic beta cells
  - Secondary failure: caused by progressive decrease in B-cell mass, reduction in physical activity, decline in lean body mass, and increase in ectopic fat deposition
  - Important drug interactions: displacement from protein binding sites, interference with hepatic metabolism, and reduction of renal elimination
Drugs that slow the absorption of starches
- Alpha Glucosidase Inhibitors (e.g., acarbose and miglitol)
  - Mechanism of action: competitive inhibitors of intestinal alpha glucosidase, reducing the postprandial digestion and absorption of starch and disaccharides
  - Clinical use: approved for use in individuals with type 2 diabetes as monotherapy and in combination with sulfonylureas
  - Adverse effects: hypoglycemia, gas, and distention, and reversible hepatic enzyme elevation
Incretin Therapy
- Incretins: naturally occurring hormones released by the gut, including GLP-1 and GIP
  - Physiologic activity: stimulates glucose-dependent insulin release, decreases glucagon production, and increases satiety
  - Diminished in type 2 diabetes: levels of GLP-1 are decreased, and insulinotropic response to GIP is diminished
- Exenatide: synthetic analogue of GLP-1, used to increase insulin release
- Sitaglaptin: drug that inhibits dipeptidyl peptidase-4, allowing endogenous incretins to act longer
Sodium Glucose Cotransporter 2 Inhibitors (SGLT-2)
- Canagliflozin, Empagliflozin, and Dapagliflozin: drugs that inhibit SGLT-2, reducing glucose reabsorption in the kidneys and increasing glucose excretion in the urine

Learn about the different classes of oral antidiabetic drugs, their mechanisms of action, and metabolism. This quiz covers biguanides, such as metformin, and their effects on glucose production and absorption.

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