1 the role of dpp-iv inhibitors in the management of type 2 diabetes
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The Role of DPP-IV Inhibitors in the
Management of Type 2 Diabetes
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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 ↓ 0.5-0.8%
• FPG ↓ 15-30 mg/dl
• PPG ↓ 34-50 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
DPP-4 Inhibitors (dipeptidyl peptidase-4 )DPP-4 Inhibitors (dipeptidyl peptidase-4 )
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The Role of GLP-1The Role of GLP-1
DPP-4 Inhibitors Increase ½ Life of GLP-1
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DPP-IV ACTIONDPP-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
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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).
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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 - superseded by synthetic analogues insulin glargine and insulin detemir, which provide a relative peakless profile , yield better reproducibility and consistency,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.
Major features of AACE 2009 Guidelines
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*Adapted from Nathan DM. N Engl J Med. 2007;356(5):437-440.
Approved Antidiabetic Medications in the United States
MedicationRoute of
AdministrationYear of Introduction
or FDA ApprovalEfficacy as Monotherapy
(% Reduction in A1C)
Insulin Subcutaneously 1921 2.5
Sulfonylureas Oral 1946 1.5
Metformin* Oral 1995 1.5
Alpha-glycosidase Inhibitors
Oral 1995 0.5-0.8
Thiazolidinediones Oral 1997 0.8-1.0
Glinides Oral 1997 1.0-1.5
GLP-1 Analogs Subcutaneously 2005 0.6
Amylin Analogs Subcutaneously 2005 0.6- 2.1
DPP-IV Inhibitors Oral 2006 0.5-0.9
Typical A1C Reduction
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Properties/Effect DPP-4 InhibitorsGLP-1 Receptor
Agonists
Glucose-dependent stimulation of insulin secretion Yes Yes
Glucose-dependent reduction of increased glucagon
Yes Yes
Slows gastric emptying No Yes
Effect on body weight Weight neutral Weight loss
Side effects Well tolerated Nausea,vomiting
Hypoglycemia No No
AdministrationOral
Once dailySubcutaneous
Once or twice daily
Major Differences in Incretin Therapies
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Short-Version AACE Guidelines, 2009