1. Therapy of Type 2 Diabetes Mellitus: UPDATE
Glycemic Goals in the Care of Patients with Type 2 Diabetes ADA and AACE Guidelines:
Room For Improvement
(Be HAPPY/ Avoid Burnout, While Caring for Patients with DM)
Stan Schwartz MD, FACP, FACE
Affiliate, Main Line Health System
Clinical Associate Professor of Medicine, Emeritus,
U of Pa.
Part 6 1

2. STRESS (peri-op) DM STORY
1. Intensive in-hosp regimens resource intensive/ inc. hypo
2. Tried incretins- saw ~33% less patients needed insulin
3. steroids/ tacrolimus dec PDX-1 in b-cell, GLP-1 increase PDX-1
4. So incretins treat 2 stress hormones

3. Glp1 in major surgery in DM Benefit in Stress/ Steroid DM

4. IV GLP-1 (3.6 pmol/kg/min =400 pmol/L)
For 12 hrs. after CABG in 20 Insulin Naive Type 2 Diabetic Patients
Insulin rescue if glucose > 140 mg% ( 7.77 mM) >3 hrs
0.005 u kg (GLP-1 group) vs 0.073u/kg (insulin group)
ie: Greater than 10 x less insulin required over 12 hrs
2. Mean glucose mg % (7.89 mM) (GLP-1 group),
146 mg % (8.12 mM) (insulin group)
AUC glucose = both groups
3. No Hypoglycemia or Nausea, even with high dose
4. Less Pressors
Mussig, j.amjcard

5. Sub-cu Exenatide in Severely Burned Pediatric Patients: equal glycemic control, but:
The use of exenatide in severely burned pediatric patients,Critical Care 2010, 14:R153,Gabriel A Mecott et al

6. Insulin Secretagogues: Sulfonylureas and “Glinides”
Safety and Efficacy
-Decreases HbA1c approx 1–2%(sfu, repaglinide)( %,neteglanide)
-Adverse events:
Wt gain,
sulfa allergy (sfu,rare),
-cell apoptosis (sfu)
Main risk = hypoglycemia , inc ischemia risk(~50% less w/repaglinide,75% less with neteglanide)
Increase Cancer vs Metformin
Abnormal ischemia pre-conditioning
SO WHY USE SOMETHING THAT DESTROYS BETA-CELLS THAT YOU’D LIKE TO SAVE
Davies MJ. Curr Med Res Opin. 2002;18(Suppl 1):s22-30. 6

7. Higher Mortality Is Associated With Greater Exposure to Sulfonylurea
There was a greater risk of death associated with higher daily doses and better adherence for patients who used glyburide (HR = 1.3; 95% CI, ), but not metformin (HR = 0.8; 95% CI, )
Glyburide
(n = 4138)
Metformin
(n = 1537)
1.32
1.29
0.92
0.96
0.84
41.5 (37.6)
53.4 (70.2)
Daily Dose
Hazard
ratio
Monotherapy
group
Deaths/1000 person-years
Lower (higher)
Glyburide
(n = 4138)
Metformin
(n = 1537)
1.55
1.34
1.33
1.10
1.09
0.98
49.0 (75.8)
37.7 (41.3)
Poor (good)
Adherence
Hazard
ratio
Monotherapy
group
Deaths/1000 person-years
Unadjusted
Adjusted for age, sex, chronic
disease score (CDS), and nitrate use
Adjusted for age, sex, CDS, nitrate use,
physician visits, and hospital admissions
A retrospective, inception cohort study conducted in 5795 new users of oral glucose-lowering medications
- Insulin or combination therapy were excluded
- Mean age: 66.3 years
- Mean follow-up: 4.6 years
- Main outcomes: all-cause mortality, death from acute
ischemic event
Simpson SH, et al. CMAJ. 2006;174:

8. CV Risk of SU and Insulin
So benefit of both SU/Insulin in
research studies –UKPDS, DCCT/EDIC
But adverse risk in ‘real world’ use
Pharmacoepidemiology and Drug Safety. 2008;(17):

9. Sulfonylureas and Ischemic Pre-conditioning

10. MUST CONSIDER TOTAL COST- Incretin vs Sulfonylureas- not per/pill
ER Visits
Hospitalizations
Mortality
Under-recognized- hypoglycemic unawareness
Lifestyle Restrictions, diminished quality of life
Worry for Spouse, Friends, Co-workers
Fear of Hypoglycemic leads to inadequate Control
Severe Hypoglycemia Raises the Risk of Dementia
Increased cost of increased number SMBG testing
And 2 Part-D insurers
now ask for prior auth
for GLYBURIDE, ? SUs
And Given Apoptosis, death of beta-cells with SU,
you’ll need expensive drugs anyway in 1-3 years- but now at disadvantage of having lost b-cell mass

11. Decrease b-cell demand- - dec CV outcomes, STOP- NIDDM
Decrease HbA1c 0.5–1%
Decrease PPG,TG
Delay DM
Adverse events: flatulence,treat hypoglycemia with glucose 11