SUMMARIZED FROM AUSTRALIAN DOCTOR DIABETES SUPPLEMENT NOV 2009
8 different classes of medications are now available for treatment of diabetes:

1. GLP-1 and DPP-IV
2. insulin 1921
3. Sulfonylureas:stimulate insulin release 1946
4. Metformin:reduced hepatic glucose production and insulin resistance 1957
5. Acarbose: reduces carbohydrate digestion 1995
6. Thiazolidinediones "glitazones": reduce insulin resistance 1997
7. Repaglinide: short term insulin stimulation 1997
8. Exenatide GLP-1 Analogue 2005
9. Sitagliptin DPP-IV inhibitor enhances GLP-1 action 2006

GLP-1 resembles the structure of glucagon but has an OPPOSITE physiological effect:

1. PROMOTES insulin secretion
2. INHIBITS glucagon release
3. REDUCES circulating glucagon levels

GLP-1 is released from the gut wall in response to food. it is degraded very rapidly by enzyme dipeptidyl peptidase-IV (DPP-IV)

New GLP-1 based therapies are: Exenatide an INJECTABLE GLP-1 analogue or mimetic, DPP-IV INHIBITORS such as sitagliptin which slow degradation of GLP-1 and boosts its effects.

LOW RISK HYPOGLYCEMIA FROM TREATMENT AS EFFECT of GLP-1 DECLINES as blood glucose levels fall.

EXENATIDE
developed from exendin-4 compound of Gila monster salivary gland.
In clinical trials: S/c EXENATIDE BID decreased HBA1C by 0.8-0.9% and associated with INCREASED SATIETY, REDUCED APPETITE, WEIGHT LOSS and low rate of hypoglycemia.

side effects"nausea, sweating, vomiting, dizziness,
weight loss 2.5kg at 12 momths using exenatide compared to 2.9kf weight gain with insulin.

PROF DRUCKER from Banting and Best Diabetes Centre in Toronto recommends: EARLY combination therapy with METFORMIN and Sitagliptin.
METFORMIN ALSO STIMULATES GLP-1 SECRETION!
GLP-1 is also CARDIOPROTECTIVE.
Sitagliptin is indicated in Australia for combination therapy woth metformin, sulfonylureas and thiazolinedinediones.

Consensus recommendations from American Diabetes Association and European Association the Study of Diabetes (Diabetes Care 2009;32:193-203):

* Tier 1 medications with well-established safety records and efficacy are diet, eexrcise, metformin, insulin and sulfonylureas.
* Tier-2 less 'well validated" are pioglitazone and GLP-1 agonist exenatide. Useful if recurrent hypoglycemia or for promotion of weight loss.
* Other therapy includes: acarbose, repaglinide, DPP-IV inhibitors such as sitagliptin.