Dpp4 inhibitors

3,824 views
3,615 views

Published on

DPP4 inhibitors

Published in: Health & Medicine
0 Comments
2 Likes
Statistics
Notes
  • Be the first to comment

No Downloads
Views
Total views
3,824
On SlideShare
0
From Embeds
0
Number of Embeds
13
Actions
Shares
0
Downloads
385
Comments
0
Likes
2
Embeds 0
No embeds

No notes for slide
  • The incretin effect is the increased magnitude of insulin secretion in response to an oral glucose load compared to the insulin secretion in response to intravenous glucose administration. The incretin effect is now known to be a direct result of gut hormones secreted in response to oral intake which have a salutary effect on nutrient handling. These hormones are collectively known as incretin hormones and the two main human incretin hormones are glucagon-like peptide-1 (GLP-1) and gastric inhibitory peptide (GIP). Exendin 4 has 50% homology with GLP-1.
    The incretin effect is blunted in individuals with Type 2 DM.
  • Quickly after it’s release GLP-1 is converted to it’s inactive form by an enzyme dipeptidyl peptidase 4.
  • Quickly after it’s release GLP-1 is converted to it’s inactive form by an enzyme dipeptidyl peptidase 4.
  • Comparative Effectiveness of Treatment Options: Intermediate Outcomes
    Intermediate clinical outcomes were the most frequently evaluated outcomes. There were 121 relevant articles with data from only randomized controlled trials that addressed either HbA1c, body weight, or lipids. Fifty-one of the studies had also been included in the 2007 CER.
    References:
    Bennett WL, Wilson LM, Bolen S, et al. Oral Diabetes Medications for Adults With Type 2 Diabetes: An Update. Comparative Effectiveness Review No. 27. (Prepared by Johns Hopkins University Evidence-based Practice Center under Contract No. 290-02-0018.) AHRQ Publication No. 11-EHC038-EF. Rockville, MD: Agency for Healthcare Research and Quality. March 2011. Available at: http://effectivehealthcare.ahrq.gov/index.cfm/search-for-guides-reviews-and-reports/?pageaction=displayproduct&productID=644.
    Bolen S, Wilson L, Vassy J, et al. Comparative Effectiveness and Safety of Oral Diabetes Medications for Adults With Type 2 Diabetes. Comparative Effectiveness Review No. 8. (Prepared by Johns Hopkins Evidence-based Practice Center under Contract No. 290-02-0018.) Rockville, MD: Agency for Healthcare Research and Quality. July 2007. Available at: www.effectivehealthcare.ahrq.gov/index.cfm/search-for-guides-reviews-and-reports/?pageaction=displayproduct&productid=40.
  • Dpp4 inhibitors

    1. 1. DPP4- inhibitors Amman-Sheraton Hotel Dr.Ibrahim Tuffaha 16-feb2014
    2. 2. Introduction Each of us—every human adult—is composed of roughly 100 trillion individual cells. Our health depends on effective communication between those cells. Over time, it has become clear that the systems that coordinate cellular activity are far more complex than we originally believed.
    3. 3. One example is the incretin hormones, such as GLP-1. These are rapidly secreted from the gut following food intake. Research continues to shed light on their role in health and disease, causing many physicians to rethink the processes underlying glucose metabolism and type 2 diabetes.
    4. 4. Prevalence of Diabetes in United States 25 20 23.6 15 10 16.1 19.3 1988-94 1999-2002 5 0 2008
    5. 5. Treatment of diabetes
    6. 6. Therapeutic Options for Type 2 DM 2008 1995 Sulfonylurea INSULIN – – – NPH Regular Ultralente Sulfonylurea INSULIN – – – – NPH Regular Insulin analogues Inhaled Metformin TZDs Alpha glucosidase inhibitors Meglitinides Endocannabinoid receptor Incretin mimetics Amylin analogues DPP IV inhibitors
    7. 7. Reduced Incretin Effect in Type 2 Diabetic Patients Control Subjects Incretin effect 40 * * * * * * * 20 0 30 60 90 120 150 180 TIME (min) INSULIN ( mU/L ) INSULIN (mU/L ) 60 0 Type 2 Diabetic Patients 80 Intravenous Glucose Oral Glucose 60 80 40 * * 20 0 0 30 * 60 90 120 150 180 TIME (min) Nauck M, et al. Diabetologia. 1986;29:46-52.
    8. 8. GLP-1 Modes of Action in Man Upon ingestion of food… GLP-1 is secreted from the L-cells in the jejunum and ileum • Slows gastric emptying • Reduces food intake • Suppresses glucagon secretion • Stimulates insulin secretion Long term effects demonstrated in animals… • Increases beta-cell cell mass and maintains beta-cell efficiency Drucker DJ. Curr Pharm Des 2001; 7:1399-1412 Drucker DJ. Mol Endocrinol 2003; 17:161-171
    9. 9. GLP-1 Secretion and Inactivation Mixed meal Intestinal GLP-1 release T1/2 = 1 to 2 min GLP-1 (7-36) active DPP-4 GLP-1 (9-36) inactive (>80% of pool) Adapted from Deacon CF, et al. Diabetes. 1995;44:1126-1131 .
    10. 10. GLP-1 Functions
    11. 11. GLP-1 Secretion and Inactivation Mixed meal Intestinal GLP-1 release T1/2 = 1 to 2 min GLP-1 (7-36) active DPP-4 GLP-1 (9-36) inactive (>80% of pool) Adapted from Deacon CF, et al. Diabetes. 1995;44:1126-1131 .
    12. 12. N.B 1-2 minutes only ;80%Glp-1 active ------to GLP-1 inactive This happened by DPP4 TO GET MORE BENEFITS OF INTERNAL GLP-1 we have to : 1)Prolong the half life 2)Decrease the amount of inacttivity
    13. 13. THIS LEADS US TO INHIBIT THE DPP4
    14. 14. DPP4 inhibitors (gliptins) is hypoglycemic class that inhibiting the action of DPP4 (which degrade the action of GLP-1 to convert it to inactive form )
    15. 15. Inhibition of DPP-4 Increases Active GLP-1 Mixed meal Intestinal GLP-1 release GLP-1 (7-36) GLP-1 (7-36) active active DPP-4 DPP-4 inhibitor GLP-1 (9-36) inactive Adapted from Rothenberg P, et al. Diabetes. 2000;49(suppl 1):A39.
    16. 16. DPP 4 Inhibitors ♦ Once daily ingestion ♦ Reduce fasting and postprandial glucose, reduce HbA1c ♦ Decrease glucagon response to ingested meal ♦ Initial studies in combination with metformin
    17. 17. DPP4 inhibitors drugs Drugs belonging to this class are : Sitagliptin[5] (FDA approved 2006, marketed by Merck & Co. as Januvia), Vildagliptin[6] (EU approved 2007, marketed in the EU by Novartis as Galvus), Saxagliptin (FDA approved in 2009, marketed as Onglyza), Linagliptin (FDA approved in 2011, marketed as Tradjenta by Eli Lilly Co and Boehringer Ingelheim),[7] Anagliptin (approved in Japan in 2012, marketed by Sanwa Kagaku Kenkyusho Co., Ltd. and Kowa Company, Ltd.)[8] Teneligliptin (approved in Japan in 2012[9]) Alogliptin (FDA approved 2013, marketed by Takeda Pharmaceutical Company) Gemigliptin (being developed by LG Life Sciences)
    18. 18. DPP-4 inhibitors (eg, sitagliptin, saxagliptin, linagliptin) are a class of drugs that prolong the action of incretin hormones. DPP-4 degrades numerous biologically active peptides, including the endogenous incretins GLP-1 and glucosedependent insulinotropic polypeptide (GIP).
    19. 19. Comparative Effectiveness of Treatment Options: Intermediate Outcomes Glycemic control (HbA1c) Weight Lipids Low-density lipoprotein (LDL) High-density lipoprotein (HDL) Triglyceride (TG)
    20. 20. Summary of DPP-4 Inhibition Increases fasting and postprandial GLP-1 levels Reduces fasting and postprandial glycemia Improves ß-cell function – Increases insulin secretion, reduces proinsulin/insulin ratio – Increases beta-cell mass Inhibits glucagon secretion – Reduces hepatic glucose production Increases insulin sensitivity Reduces postprandial lipemia No effect on gastric emptying or body weight Reduces HbA1c by ~1% Is safe and tolerable in short term In renal impairment, dose decreased by 50%
    21. 21. DPP-4 inhibitors can be used as a monotherapy or in combination with Metformin or a TZD. They are given once daily and are weight neutral.
    22. 22. A study shows that added to insulin (with or without Metformin ) decrease FBS by 15 mg/dl And decrease 2h PPBS by 36 mg /dl
    23. 23. In nephropathy it is safe to use DPP4 inhibitor as GFR >30 ml /min with halving the dose In ESRD linagliptin and sitagliptin only used
    24. 24. The clinical observations that DPP4inhibitors associated with pancreatitis or pancreatic cancer is refused by ADA because no proofs. But they suggesting not to use in patient who has pancreatitis
    25. 25. Clinically observed that upper respiratory infection is related to the use of DPP4 inhibitors . On the other hand, a meta-analysis suggested that treatment with DPP-4 inhibitors could reduce the risk of bone fractures.

    ×