Dpp – 4 inhibitors
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DPP-4 inhibitors work by inhibiting the breakdown of the incretin hormones GLP-1 and GIP, prolonging their effects and enhancing insulin secretion. They reduce blood glucose levels with a low risk of hypoglycemia and are weight neutral. Several DPP-4 inhibitors are available or in development for treating type 2 diabetes, including sitagliptin, saxagliptin, and linagliptin. DPP-4 inhibitors offer an effective treatment either alone or in combination with other drugs, with advantages like fewer side effects, safety in hepatic or renal impairment, and possible cardiovascular benefits. More research is still needed to fully evaluate their long-term safety profile.
Dpp – 4 inhibitors
- 1. DPP – 4 Inhibitors : Mechanism of Action& Role in DM - 2 Management Dr. Arun Sharma
- 2. BRIEF INTRODUCTION : T2DM Prevalent chronic healthcare disease with a significant global disease burden. Achieving specific glycemic goals substantially reduces morbidity & have made the effective treatment of hyperglycemia a top priority. Intensive glycemic control has a powerful beneficial effect on diabetes-specific complications. Development of new classes of blood glucose- lowering medications has increased the number of treatment options.
- 3. DPP-4 Inhibitors : A Novel approach in T2DM Management DPP 4 inhibitors inhibit the breakdown of Incretin peptide hormones and increase the Incretin effect in patients with type 2 DM. Their development was based on observations that factors secreted from gut participated in regulation of pancreatic endocrine secretion.These gut factors were termed “Incretins”. Two Incretin peptide hormones have been identified in humans,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. Incretins and glycemic control Adapted from 7. Drucker DJ. Cell Metab. 2006;3:153–165. 8. Miller S, St Onge EL. Ann Pharmacother 2006;40:1336-1343. Active GLP-1 and GIP Release of incretin gut hormones Pancreas Blood glucose control GI tract Glucagon from alpha cells (GLP-1) Glucose dependent Alpha cells Increased insulin and decreased glucagon reduce hepatic glucose output Glucose dependent Insulin from beta cells (GLP-1 and GIP) Beta cells Insulin increases peripheral glucose uptake Ingestion of food DPP-4 enzyme rapidly degrad es incretins
- 6. DPP – 4 Inhibitors in Clinical Practice A 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 used either as monotherapy or in combination with Metformin, Sulphonylureas or a combination of both. They are also associated with lower rates of hypoglycemia and have also been shown to be weight neutral.
- 8. Advantages of Using DPP – 4 Inhibitors As Monotherapy : Shown to be equally efficacious as compared to other antidiabetic agents with added advantage of lesser incidence of hypoglycemia and being weight neutral. As Initiation Therapy : Can be safely coupled with Metformin as an Inititaion therapy 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 given safely with anti-hypertensives,anti-hyperlipidemics & antibiotics. Cardiac friendly profile :Studies suggest that DPP-4 inhibitors have a cardiovascular friendly profile. Preclinical studies have suggested endothelial benefit, anti-atherosclerotic effects and blood pressure lowering effects.
- 9. Advantages of Using DPP – 4 Inhibitors : Continued Safe in Hepatic Inefficiency : For patients with hepatic insufficiency, except for vildagliptin, no dose adjustment is necessary for gliptins. Safe in Renal Insufficiency :Linagliptin is safe in renal insufficiency.Other gliptins can be used safely with dose adjustments. Well Tolerated in most people with not much significant adverse event profile.
- 10. Conclusion Need for newer medications in T2DM Management. DPP - 4 Inhibitors offer a promising treatment modality in T2DM. Need for continued research to evaluate long term safety and adverse event profile in patients.
- 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. THANK YOU Dr. Arun Sharma M.B.B.S.
Editor's Notes
- #5: 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.