Dpp – 4 inhibitors

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dpp - 4 inhibitors are a newer class of drugs for management of type 2 diabetes mellitus.

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  • Drucker DJ. The biology of incretin hormones. Cell Metabolism 2006;3:153-165. Miller S, St Onge EL. Sitagliptin: A dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes. Ann Pharmacother 2006;40:1336-1343.
  • Dpp – 4 inhibitors

    1. 1. DPP – 4 Inhibitors :Mechanism of Action& Rolein DM - 2 ManagementDr. Arun Sharma
    2. 2. BRIEF INTRODUCTION : T2DM Prevalent chronic healthcare disease with a significantglobal disease burden. Achieving specific glycemic goals substantiallyreduces morbidity & have made the effective treatmentof hyperglycemia a top priority. Intensive glycemic control has a powerful beneficialeffect on diabetes-specific complications. Development of new classes of blood glucose-lowering medications has increased the number oftreatment options.
    3. 3. DPP-4 Inhibitors : A Novelapproach in T2DM Management DPP 4 inhibitors inhibit the breakdown of Incretin peptide hormonesand increase the Incretin effect in patients with type 2 DM. Their development was based on observations that factorssecreted from gut participated in regulation of pancreatic endocrinesecretion.These gut factors were termed “Incretins”. Two Incretin peptide hormones have been identified inhumans,namely Glucose dependent insulin releasing polypeptide(GIP) and Glucagon like peptide -1 (GLP-1) Incretins are rapidly inactivated by dipeptidyl peptidase-4 (DPP-4).The DPP-4 inhibitors prolong the action of endogenous incretins,enhancing the first-phase insulin response.
    4. 4. Incretins and glycemiccontrolAdapted from 7. Drucker DJ. Cell Metab. 2006;3:153–165. 8. Miller S, St Onge EL. Ann Pharmacother 2006;40:1336-1343.ActiveGLP-1 and GIPRelease ofincretin guthormonesPancreasBloodglucosecontrolGI tract Glucagonfrom alpha cells(GLP-1)GlucosedependentAlpha cellsIncreased insulinand decreasedglucagonreducehepaticglucose outputGlucose dependent Insulinfrom beta cells(GLP-1 and GIP)Beta cellsInsulinincreasesperipheralglucoseuptakeIngestionof foodDPP-4enzymerapidlydegradesincretins
    5. 5. Functions of Incretins
    6. 6. DPP – 4 Inhibitors in ClinicalPracticeA list of available and expected gliptins : Sitagliptin (Merck Sharp and Dohme Corp, approved as Januvia by US FDA in year 2006) Vidagliptin (Novartis, approved as Galvus by EU in year 2007) Saxagliptin (Bristol-Myers Squibb, approved as Onglyza by US FDA in 2010) Linagliptin (Boerhinger Ingelheim, approved as Tradjenta by US FDA in year 2011) Alogliptin (developed by Takeda Pharmaceutical Company Limited, approved for use in Japan) Dutogliptin (being developed by Phenomix Corporation) Gemigliptin (being developed by LG Life Sciences) Linagliptin has recently been approved in India. In clinical trials,most of these drugs have been shown to reduce HbA1c significantly when usedeither as monotherapy or in combination with Metformin, Sulphonylureas or a combination ofboth. They are also associated with lower rates of hypoglycemia and have also been shown to beweight neutral.
    7. 7. Comparative PharmacokineticProfile
    8. 8. Advantages of Using DPP – 4Inhibitors As Monotherapy : Shown to be equally efficacious as compared to otherantidiabetic agents with added advantage of lesser incidence ofhypoglycemia and being weight neutral. As Initiation Therapy : Can be safely coupled with Metformin as an Inititaiontherapy as per the latest guidelines (ADA guideline) Insulin dose can be reduced if given with gliptins as a combination therapy. No significant drug – drug interaction with other drugs so can be givensafely with anti-hypertensives,anti-hyperlipidemics & antibiotics. Cardiac friendly profile :Studies suggest that DPP-4 inhibitors have acardiovascular friendly profile. Preclinical studies have suggestedendothelial benefit, anti-atherosclerotic effects and blood pressure loweringeffects.
    9. 9. Advantages of Using DPP – 4Inhibitors : Continued Safe in Hepatic Inefficiency : For patients with hepaticinsufficiency, except for vildagliptin, no dose adjustmentis necessary for gliptins. Safe in Renal Insufficiency :Linagliptin is safe in renalinsufficiency.Other gliptins can be used safely with doseadjustments. Well Tolerated in most people with not much significantadverse event profile.
    10. 10. Conclusion Need for newer medications in T2DMManagement. DPP - 4 Inhibitors offer a promising treatmentmodality in T2DM. Need for continued research to evaluate longterm safety and adverse event profile inpatients.
    11. 11. References Indian Journal Of Endocrinology &Metabolism 2011 Oct-Dec; 15(4): 298–308. www.Diabetesincontrol.com www.diabetesjournals.org www.qjmed.oxfordjournals.org
    12. 12. THANK YOUDr. Arun SharmaM.B.B.S.

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