1. The Role of DPP-IV Inhibitors in the Management of Type 2 Diabetes

2. DPP-4 Inhibitors (dipeptidyl peptidase-4 )
Januvia (sitagliptin), Onglyza (saxagliptin), Tradjenta (Linaglipitin)
MOA: dipeptidyl peptidase-4 inhibitor, blocks the breakdown of GLP-1 in small intestine increasing concentration in the bloodstream
A1c ↓ %
FPG ↓ mg/dl
PPG ↓ mg/dl
Dosing: sitagliptin 50 or 100 mg daily, saxagliptin 2.5 or 5 mg daily, linaglipitin 5 mg daily (Taken with or without food)
Side Effects: Possible hypoglycemia when used with insulin or insulin secretagogues
Often added to metformin for maximum effect

3. DPP-4 Inhibitors Increase ½ Life of GLP-1
The Role of GLP-1
DPP-4 Inhibitors Increase ½ Life of GLP-1

4. X DPP-IV ACTION Cleaves GLP-1
Results in decreased signal to the pancreas—limiting insulin response.
That in turn decreases the signal to the liver resulting in increased hepatic glucose production.
HYPERGLYCEMIA X

7. Major features of AACE 2009 Guidelines
1. Most Important Principle : recognition
of the importance of avoiding hypoglycemia (24-28) .
2. It favors the use of GLP-1 agonists and
DPP-4 inhibitors with higher priority-
effectiveness and overall safety profiles.
3. It moves sulfonylureas to a lower priority because of the
associated risks
a. hypoglycemia
b. weight gain
c. glycemic control only for relatively short
period (1 to 2 years in typical patients).

8. Major features of AACE 2009 Guidelines
5. TZDs as “well-validated”, effective durable
6. It considers 3 other classes of agents (AGIs, cole- sevelam, and glinides) only for relatively narrow, well-defined clinical situations in view of their limited efficacy.
7. Rapid-acting insulin analogues are superior to “regular human insulin” - safer alternative.
8. NPH insulin is not recommended. - superseded by
synthetic analogues insulin glargine and insulin detemir, which provide a relative peakless profile , yield better reproducibility and consistency, corresponding reduction in the risk of hypoglycemia.

9. Typical A1C Reduction Key Points
Approved Antidiabetic Medications in the United States
Year of Introduction or FDA Approval
Efficacy as Monotherapy
(% Reduction in A1C)
Medication
Route of Administration
Insulin
Subcutaneously
1921
2.5
Sulfonylureas
Oral
1946
1.5
Metformin*
Oral
1995
1.5
Alpha-glycosidase Inhibitors
Oral
1995
Thiazolidinediones
Oral
1997
Glinides
Key Points
Insulin treatment produces the greatest reduction in A1C as monotherapy
Sulfonylureas (50 years) and biguanides (1995) also produce a significant reduction
Reference
Nathan DM. Finding new treatments for diabetes—how many, how fast … how good? N Engl J Med. 2007;356(5):
Oral
1997
GLP-1 Analogs
Subcutaneously
2005
0.6
Amylin Analogs
Subcutaneously
2005
DPP-IV Inhibitors
Oral
2006
*Adapted from Nathan DM. N Engl J Med. 2007;356(5):

10. Major Differences in Incretin Therapies
Properties/Effect
DPP-4 Inhibitors
GLP-1 Receptor Agonists
Glucose-dependent stimulation of insulin secretion
Yes
Glucose-dependent reduction of increased glucagon
Slows gastric emptying No
Effect on body weight
Weight neutral
Weight loss
Side effects
Well tolerated
Nausea,vomiting
Hypoglycemia
Administration
Oral
Once daily
Subcutaneous
Once or twice daily

11. Short-Version AACE Guidelines, 2009