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

2. Mission and Vision
Our Vision To be a world class referral hospital in the provision of innovative and specialised healthcare Mission To provide accessible specialised quality healthcare, facilitate medical training, research and to participate in national health planning and policy

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

4. 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

5. 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)

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

7. 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

8. 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 %
Can be used in renal failure

9. 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

10. 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

11. 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

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

13. 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

14. 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

15. 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

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

17. THANK YOU ALL