Transcript The Present and Future of Insulin Therapy in the Era of

Current Therapy for
Type II Diabetes
New ADA Guidelines- 4/20/12
SU most
prominentFirst,
reading L to R
Added back
glyburide
Inzucchi,
Diabetologia
4/20/12
Non-Insulin Therapy for Hyperglycemia in Type 2 Diabetes,
Treating Defronzo’s Octet:
Match Patient Characteristics to Drug Characteristics
5.Gut CHO
Absorption:
8.Kidney-
SGLT2
-
Incretin,
Pramlintide,
Glucosidase inh.
1.Pancreatic
insulin
Secretion:
Incretin, ranolazine
2.Pancreatic
glucagon
Secretion- Incretin
7.BrainTZD,INCRETI
bromocryptine
HYPERGLYCEMIA
De
-
-
3.Muscle-
TZD, Incretin
4.Liver
Hepatic glucose
production:
Metformin, incretin
Peripheral
glucose
uptake
6.Fat- TZD, metformin
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
Lifestyle Modifications
A1C 6.5%-7.5%
A1C 7.6%-9.0%
If under
treatment
Monotherapy
Dual therapy
Insulin plus
other
agent(s)*
Dual therapy
Triple therapy
A1C > 9.0%
Triple therapy
If drug
naive
Insulin plus
other
agent(s)*
Use Sulfonylureas/Glinides LAST, IF AT ALL
Triple therapy
Therapeutic Choice, based on Safety/ Efficacy,
Should Match The Drug Characteristics With Patient Characteristics
Rodbard HW, et al. Endocr Pract. 2009;15:540-559.
Issues
1. Tells you CONSIDER stopping SU- MUST
2. Doesn’t tell you what to do with other non-insulin therapies-CONTINUE
3. 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
Hypoglycemia
CONCLUSION:
DELAY INSULIN
THERAPY;
AVOID BOLUS
RX if possible
NORMAL:
Insulin into portal
system
B-cell=
Perfectand
glucose
sensorExogenous Insulin
Insulin secretion modulato
Philosophy for Reduced Insulin
Need
in
T2DM
1. No Perfect Insulin
Exogenous insulin not put in portal system; no fine-tuning a la Beta Cell
2. Leads to Hyperinsulinismleads 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
Colsevalam, ranolazine, AGI
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