Current Therapy for Type II Diabetes

New ADA Guidelines- 4/20/12

Inzucchi,Diabetologia4/20/12

SU most prominent-First, reading L to R

Added back glyburide

Non-Insulin Therapy for Hyperglycemia in Type 2 Diabetes,Treating Defronzo’s Octet:

Match Patient Characteristics to Drug Characteristics

5.Gut CHOAbsorption:

Incretin,Pramlintide,Glucosidase inh.

Peripheralglucose uptake

--

-

1.Pancreatic insulin

Secretion:Incretin, ranolazine

2.Pancreatic glucagon

Secretion- Incretin

HYPERGLYCEMIA

6.Fat- TZD, metformin

7.Brain-TZD,INCRETIN,bromocryptine

8.Kidney-

SGLT2

3.Muscle- TZD, Incretin

4.Liver

Hepatic glucose production:

Metformin, incretin

De

AACE/ACE: Recommendations Based on A1C at Diagnosis/ or When you see in Office

EMPHASIS on Using Combination Therapy to ADDRESS multiple etiologies of hyperglycemia in Octet

Rodbard HW, et al. Endocr Pract. 2009;15:540-559.

A1C 6.5%-7.5% A1C 7.6%-9.0% A1C > 9.0%If undertreatment

If drugnaive

Insulin plusother

agent(s)*Insulin plus

other agent(s)*

Symptoms

No sy

mpt

oms

Lifestyle Modifications

Use Sulfonylureas/Glinides LAST, IF AT ALL

Monotherapy

Dual therapy

Triple therapy

Dual therapy

Triple therapy

Triple therapy

Therapeutic Choice, based on Safety/ Efficacy, Should Match The Drug Characteristics With Patient Characteristics

Issues1. Tells you CONSIDER stopping SU- MUST2. Doesn’t tell you what to do with other non-insulin therapies-CONTINUE3. Doesn’t tell you use other non insulin agents before use prandial insulin since >80 % (conservative) of type 2 pts won’t require bolus insulin if on GLP-1 RA with

SGLT-2 inhibitor +/- other

There is No perfect Exogenous Insulin:All result in HyperInsulinemia and Potential Hypoglycemia

Exogenous Insulin

Perfect glucose sensor-Insulin secretion modulator

Hypoglycemia

NORMAL:Insulin into portal system

and B-cell=

CONCLUSION:DELAY INSULIN THERAPY;AVOID BOLUS RX if possible

Philosophy for Reduced Insulin Need in T2DM

1. No Perfect InsulinExogenous insulin not put in portal system; no fine-tuning a la Beta Cell

2. Leads to Hyperinsulinism- leads to Insulin Resistance (suppresses dopamine in ‘biologic clock’ of hypothalamus)– leads to Increased Weight, Hypoglycemia Risk

3. So Goal of all Insulin Therapy- Least Hypoglycemia, Least Weight Gain

4. Old Logic- use Early Insulin to reduce Glucotoxicity, Lipotoxicity but GLP-1 RAs and SGLT-2 Inh. do that first day!!, with no weight gain, no hypoglycemia

5. Therefore no need for Early Insulin- use 3-4 Non-Insulin therapy before go to Basal Insulin;

keep Non-Insulin Therapies and 95% of T2DM won’t need Bolus Insulin (by avoiding bolus insulin reduce hypoglycemic risk 85%)

Uses Across Continuum of Care

1. Pre-Diabetes

2. Rest of Continuum of Care

3. AACE Guidelines, Triple RX before Insulin Pick Right Drug for Right Patient

4. Delay Need for Insulin No need for Early Insulin

5. If need Insulin, Continue Non-Insulin RX Avoids need for Meal-Time Insulin Decrease Risk Hypoglycemia 85%

6. Get Patients off insulin Had been given Early Insulin

Colsevalam, ranolazine, AGI