What is the general mechanism of action of Metformin?
Metformin Inhibits Excessive Glucose Output from the Liver in Type 2 Diabetes - Metformin does not have this effect on a non-diabetic because it works on glucose excess.
What is the net result of Metformin use?
Decrease in plasma glucose
In what way is Metformin "better" than insulin?
Metformin is less likely to cause weight gain and little potential to cause hypoglycemia
What side effects are associated with Metformin?
- Nausea, vomiting, diarrhea
- In a small percentage of cases, Metformin can cause lactic acidosis.
Due to the potential for lactic acidosis in Metformin, in what patients should Metformin be cautiously used?
The possibility of lactic acidosis should be considered in patients with impaired hepatic or renal function and in alcoholics, since lactic acid clearance might be decreased. This possibility should also be considered in patients with diseases associated with hypoxia (e.g., cardiac insufficiency), as there might be an increased tendency for lactic acid accumulation.
In what conditions does the risk of lactic acidosis increase?
- sepsis, dehydration, excess alcohol intake, hepatic impairment, renal impairment, and acute congestive heart failure.
What is the difference in response to insulin between type 1 and 2 diabetics?
Type 2 diabetics respond less briskly to insulin (due to insulin resistance)
What is the overall effect of sulfonylureas?
Sulfonylureas enhance insulin secretion from the pancreas
What is the mechanism of action of sulfonylureas?
Sulfonylureas stimulate pancreatic beta cells to release preformed insulin.
- This is accomplished by binding to a cell surface sulfonylurea receptor, which regulates the potassium channels in the beta-cell membrane.
- Inhibition of the K+ channels by sulfonylureas results in depolarization of the pancreatic beta cell, which results in Ca++- triggered exocytosis of insulin.
Why do sulfonylureas work in type 2 diabetics but NOT in type 1 patients?
These agents can be used in Type 2 diabetic patients in whom the pancreas maintains the capacity to produce, store, and release insulin. - Type 1 diabetics cannot produce insulin and so sulfonylureas are ineffective.
Which drug complements the actions of sulfonylureas?
Metformin works in a synergistic and additive way with sulfonylureas
What side effects are associated with sulfonylureas?
- Hypoglycemia, which may be more difficult to overcome with long acting sulfonylureas
- Difficulty losing weight
- Primary failure (no response to sulfonylureas)
- hematological or hepatic effects, CNS effects (dizziness, confusion), and dermatological effects (rash)
How do various members of the sulfonylurea family differ?
Sulfonylureas Differ in Their Duration of Action
Secretion of what type of proteins is deficient in type 2 diabetics?
Secretion of Incretins such as GLP-1 is Defective in Type 2 Diabetic Patients
What is the general effect of exenatide?
Exenatide is an Analog of the Incretin GLP-1 and Enhances Insulin Secretion
Exenatide causes a further decrease in HbA1c when used in conjunction with which other drugs?
Metformin or Sulfonylureas (both OR separately)
What are the major side effects of exenatide?
- loss of appetite
- diarrhea, heartburn, indigestion, nausea, and vomiting
What is the general effect of thiazolidinediones?
Thiazolidinediones Enhance the Sensitivity of Target Tissues to Insulin
What is the mechanism of action of thiazolidinediones?
Thiazolidinediones (TZD) bind to a transcriptional regulator (PPAR) and change transcriptional response
What side effects are associated with thiazolidinediones?
- liver toxicity
- weight gain
- fluid retention
In which patients should thiazolidinediones be used cautiously?
- patients with increased risk of heart failure
What should be monitored in patients using thiazolidinediones?
- liver function should be monitored
Summary table of diabetes drugs.
What is the best low-cost, low-risk, - high efficacy drug for type 2 diabetes?
Metformin is the best available combination of low-cost, low-risk, high-efficacy oral therapy for type 2 diabetes mellitus.
What is the best add on drug to metformin?
The lowest-cost oral add-on drug to metformin is a sulfonylurea.