1. Lifestyle Modifications
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%
A1C > 9.0%
If under
treatment
If drug
naive
Symptoms
No symptoms
Monotherapy
Dual therapy
Triple therapy
Dual therapy
Insulin plus
other
agent(s)*
Insulin plus
other
agent(s)*
Triple therapy
Triple therapy
Use Sulfonylureas/Glinides LAST, IF AT ALL
Therapeutic Choice, based on Safety/ Efficacy,
Should Match The Drug Characteristics With Patient Characteristics
Rodbard HW, et al. Endocr Pract. 2009;15: 1

2. 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

3. There is No perfect Exogenous Insulin: All result in HyperInsulinemia and Potential Hypoglycemia
CONCLUSION:
DELAY INSULIN THERAPY;
AVOID BOLUS RX if possible
NORMAL:
Insulin into portal system
and B-cell=
Perfect glucose sensor-
Insulin secretion modulator
Exogenous Insulin

4. 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 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%)

5. 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