1. ORALHYPOGLYCEMIC AGENTS

2. INTRODUCTIONDiabetesTypes 1, 2, othersPathogenesisDiagnostic criteria 3. TREATMENT CAREINSULINORAL HYPOGLYCEMICS 4. ORALHYPOGLYCEMICS 5. BIGUANIDESSECRETAGOGUESTHIAZOLIDINEDIONESACARBOSEOTHERS 6. BIGUANIDESPhenformin, MetforminNo hypoglycemiaImprove lipid profileWeight loss 7. Dose- 500 mg once to max 1000 mg bidSMBG, 2-3 weeks (slow action, gi side effects)Monotherapy effectiveOr combine with others 8. Mechanism of actionHepatic gluconeogenesis decreasedInsulin mediated glucose disposalRetard intestinal absorptionInterfere with mitochondrial respiratory chain 9. Adverse effectsNausea, pain abdomen, metallic taste, diarrhoea, anorexiaB12 deficiencyLactic acidosisCareful in alcoholics, renal failure, hepatic disease, hypotensive states, radiographic contrasts, if nil orally 10. SECRETAGOGUES 11. Sulfonylureas - MechanismSUR 1 RECEPTORSDecrease conductance of ATP sensitive K+ channelsDepolarization of beta cellsDecrease glucagon release 12. 1 st generationChlorpropamide, Tolbutamide, TolazamideLonger half-lifeMore hypoglycemiaMore side effects 13. 2 nd generation Type 2 DM of recent onset Reduce both fasting and PP glucose Start at low doses increase after1-2 weeks interval Just before a meal increase insulinacutely(With chronic therapy more sustained release) 14. 2nd generation 15. Adverse effectsHypoglycemia may recurWeight gainAvoid in renal/liver diseaseTolbutamide- reduces iodine uptakeChlorpropamide- cholestatic jaundice, hyponatremia 16. Drug Interactions - positiveProtein binding salicylates, sulfonamidesDecrease metabolism warfarin, acute alcoholSynergise salicylates, lithium, theoph ylline 17. Drug Interactions - negativeInducers Phenobarbitone, Phenytoin,Chronic alcohol, rifampicinOpposers steroids, thiazides, OCPs 18. Same channel in myocardiumAll except glyburide have a low affinity for thisNO INCREASED CARDIAC MORTALITY 19. Non-sulfonylureasMeglitinide RepaglinideD-phenylalanineanalogue Nateglinide 20. Rapid onset, short-lasting insulin releaseBefore every mealOmit if skip mealLow risk of hypoglycemiaSide effects Mild headache, dyspepsia, weight gain, avoid in liver/renal disease, arthralgia 21. THIAZOLIDINEDIONES 22. PPAR-gamma receptors (adipocytes)Insulin SENSITISERSLower insulin resistance & requirementRedistribute fat from central to peripheralOvulation in PCOS 23. Used as supplements with others in type 2Sometimes monotherapy in mild with diet, exerciseDecreased mortality due to MI/StrokeNON-RESPONDERS With low baseline insulin 24. DOSERosiglitazone 2-8 mg/day once or in 2 divided dosesPioglitazone 15-45 mg/day once daily 25. ADVERSE EFFECTS 26. Troglitazone Liver failure(monitor LFT)Effect on lipid profilePeripheral edema, CHF,weight gain, ANEMIA, Fractures, macular edemaRosiglitazone CARDIAC 27. Pioglitazone failure of OCP therapyKetoconazole inhibits metabolism of pioglitazoneLess interactions with rosiglitazone 28. ALPHA-GLUCOSIDASE INHIBITORS 29. ACARBOSEREVERSIBLE inhibitionDecrease post-prandial hyperglycemiaANTI-HYPERGLYCEMIC (NOT HYPOGLYCEMIC)Weight, TG levels decrease with chronic therapy (HbA1c less)Stop-NIDDM trial in pre- diabetics, REDUCED DM 2, HTN, CARDIOVASCULAR 30. Role as adjuvant in obese diabeticsStart at 25 mg evening50-100 mg with each meal max doseMiglitol more potent in inhibiting sucrase 31. Adverse effectsFLATULENCEABDOMINAL DISCOMFORTLOOSE STOOLS( DUE TO FERMENTATION OF UNABSORBED CARBOHYDRATES) 32. NOTE:Gradual upward dose titrationAvoid in IBD, gastroparesisIf hypoglycemia from other treatments occurs while taking these agents, use glucose 33. RECENTADVANCES 34. BROMOCRIPTINEImproves glycemic control in obese DM2Reduces both fasting and PP glucose levels 35. INCRETIN EFFECT 36. GLP-1, GIPDPP 4 37. DPP 4 inhibitorsSITAGLIPTANVILDAGLIPTANSaxagliptanRitagliptanAlogliptan 38. AMYLIN EFFECT 39. COLESEVELAMBile acid sequestrantMechanism not knownAdverse effects Constipation, dyspepsia, intestinalobstruction, nausea, painabdomen 40. RENAL GLUCOSETRANSPORTERINHIBITORSPhlorozinDapagliflozinSergliflozinRemogliflozin 41. RESVERATROLNatural compound found in grape skinFood sensors activated in shortage of food like IGF & TORMimic effect of dietary restrictionIncrease longeivity 42. SALSALATEWall Street Journal Health Blog research on using Salsalate to prevent or treat type II diabetes:Fasting glucose levels of those who took salsalate declined 13% compared with those who took a placebo 43. GLUCOKINASEACTIVATORSPIRAGLIATINHypoglycemia, fatty liver & hyperlipidemia 44. THANK YOU