Transcript NEW ORAL AGENTS IN DIABETES MANAGEMENT

DR WK SIGILAI
Consultant physician,KNH
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
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
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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
THANK YOU ALL