NEW ORAL AGENTS IN DIABETES MANAGEMENT DR WK SIGILAI Consultant physician,KNH

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Outline Introduction Classification of oral agents Newer agents New Type 2 DM care guidelines

Introduction Type 2 DM Chronic disease defined by hyperglycemia Is a syndrome of insulin resistance, insulin deficiency and ,↑hepatic glucose output It’s a ‘moving target’ Medications designed to correct one or more disorders Difficult to achieve Rx targets

Classification of oral agents There are 7 agents available: Sulphonylureas(SU) Biguanides Meglitinides Thiazolidinediones(TZD) Alpha-Glucosidase inhibitors Dipeptidyl peptidase -4 inhibitors(DPP4) Glucagon -like peptide-1 analogues(GLP-1), Gastric inhibitory polypeptide(GIP)

SULPHONYLUREAS In use since the 1950s Very widely used to date Insulin secretagogues Progressive failure as DM advances

SU Classes; 1st generation: Tolbutamide & chlorpropamide Both have fallen out of favour due to an excess of hypo complication 2nd Generation: Glibenclamide, Gliclazide, Glipizide and Glimepiride

MEGLITINIDES These are insulin secretagogues. Bind to SU receptors but at a different site Repaglinide and Nateglinide Need β-cell function Faster onset and shorter duration of action Reduce HbA1C by 0.5 - 2% Can be used in renal failure

THIAZOLIDINEDIONES Act as insulin sensitizers at peripheral sites Only Pioglitazone licensed for use Act through intracellular enzyme systems Very slow onset , optimal action takes 2-3 months, Used in combination therapy with SU, metformin Emerging reports of Ca bladder with pioglitazone

Incretins Gut hormones secreted in response to oral glucose There are 2, GLP-1 and GIP Regulate glucose disposal They have common pancreatic effects Deactivation by DPP4 enzymes GLP1 is insulinotropic in T2DM GIP is ineffective in T2DM which is detrimental

GLP-1 agonists Available since 2005, Glucagon-like mimetic Exenatide Given by subcut injection . Potent long acting agonist of GLP-1 receptor In combination with SUs/Metformin

Exenatide Good alternative to insulin Risk of hypoglycemia GI side effects are common Long term safety unknown

Dipeptidyl peptidase -4 inhibitors Sitagliptin and Vildagliptin are examples Increase insulin secretion and reduce glucagon levels Used in combination with SU, Metformin or TZD Only Sitagliptin is licensed for use with insulin GI side effects

New IDF Guidelines ADA issued in April 2012 newT2DM guidelines tailoring treatment to individual patient Due to many agents there is confusion on optimal Rx There is uncertainty over micro-, Macrovascular dx vs intensive Rx

Recommendations Reduce HbA1C to <7.0% Target A1C 6-6.5% in ; - new onset diabetes, - longer life expectancy & no CVD Target A1C 7.5-8% in - @ risk of hypoglycemia - shorter life expectancy

Recommendation New cases with A1C< 7.5% and motivated give 3-6/12 of intensive lifestyle Rx first

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