By: Ruchit Shah
Adjunctive therapy for diabetes mellitus (type 2) and
related diseases. Rosiglitazone (Avandia) Pioglitazone (Actos)
Thiazolidinediones or TZDs act by binding to PPARs
(peroxisome proliferator-activated receptors).
Specifically PPARγ
The normal ligands for these receptors are free fatty
acids (FFAs) and eicosanoids. When these receptors are activated, transcription of several insulin responsive genes is enhanced. Insulin resistance is reversed in reponse by stimulating GLUT4 expressoin and translocation (glucose and fat enters the muscle)
By activating PPARγ:
Insulin resistance is decreased Adipocyte differentiation is modified VEGF-induced angiogenesis is inhibited Leptin levels decrease (leading to an increased appetite) Levels of certain interleukins (e.g. IL-6) fall
Proglitazaone:
lowers serum triglyceride level and raises HDL level
without much change in LDL.
Rosiglitazone: inconsistent effect on lipid profile
Plasma volume exapnsion edema Weight gain, headache, myalgia, and mild anemia. Hepatic dysfunction and cardiovascular events (rare) Monitoring of liver function is advised. CI/DI:
liver disease and CHF Failure of Ocs with pioglitazone therapy. Ketoconazole inhibits metabolism of pioglitazone
New adjunct treatment for both diabetes type 1 and 2. Derived from amylin, a hormone that is released into
the bloodstream in a similar pattern as insulin, after a meal. Like insulin, amylin is deficient in individuals with diabetes. MOA:
Absorption of glucose by slowing gastric emptying, Promotes satiety center,
Inhibits inappropriate secretion of glucagon,
Type 1 and Type 2 Diabetes. Results in weight loss, allows patients to use less
insulin, lowers average blood sugar levels. Symlin is the only drug approved by the FDA to lower blood sugar in type 1 diabetics since insulin's discovery in the early 1920s.
Incretin mimetic Injected twice daily (s.c) using a pre-filled pen device. Use:
Adjunctive therapy to in patients with type 2 diabetes.
(with a combination of metformin and sulfonylurea) Some physicians are using exenatide as primary monotherapy, although this is not currently an FDA approved usage.
Note: Since the major action of this drug is to enhance
the release of endogenous insulin from the pancreas, exenatide is not used in Type 1 diabetes.
Increases insulin secretion in response to eating meals. Suppresses pancreatic release of glucagon in response
to eating helps stop the liver from overproducing sugar when it is unneeded. Helps slow down gastric emptying and thus decreases the rate at which meal-derived glucose appears in the bloodstream. Subtle yet prolonged effect to reduce appetite and thus may prevent weight gain. Exenatide reduces liver fat content.
May increase risk of sulfonylurea-induced
hypoglycemia. Gastrointestinal side effects. (Not fully understood) Patients taking exenatide (Byetta) may be at risk for acute pancreatitis according to.
Is an oral antihyperglycemic. Anti-diabetic drug of the dipeptidyl peptidase-4 (DPP-
4) inhibitor class of drugs. Use:
Type 2 diabetes mellitus.
The benefit of this medicine is its lower side-effects
(e.g., less hypoglycemia, less weight gain) in the control of blood glucose values.
Competitive inhibitor of dipeptidyl peptidase 4 (DPP-4). This enzyme breaks down the incretins GLP-1 and GIP,
gastrointestinal hormone that are released in response to a meal. By preventing GLP-1 and GIP inactivation, GLP-1 and GIP are able to potentiate the secretion of insulin and suppress the release of glucagon by the pancreas. This drives blood glucose levels towards normal. As the blood glucose level approaches normal, the amounts of insulin released and glucagon suppressed diminishes thus tending to prevent an "overshoot" and subsequent low blood sugar (hypoglycemia) which is seen with some other oral hypoglycemic agents.
Nausea and common cold-like symptoms, Hypersensitivity reactions include anaphylaxis,
angioedema, rash, urticaria, and exfoliative skin conditions including Stevens-Johnson syndrome