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 7 1

2. Renal Threshold
SGLT-2 Inh.
SGLT-2
Inhibitors DM
NML 80
SGLT2-I

3. 40-50% efficient as hepatic glucose production increased;
Obviate with incretin Rx-
yielding up to 1% drops
Durable up to 1 year

4. Canagliflozin Efficacy

5. Side Effects SGLT-2 Inhibition
cana
cana
cana
Minimize by- push PO intake, fastidious bathroom habits; urinate after intercourse
before sleep
If baseline BP low- cut back or d/c diuretic or antihyperetensive
Watch K+, if older, eGFR 45-60, on ACE / spironolactone

6. Other Meds with Glycemic Benefit
Fast-acting Bromocryptine- drop 0.5-1%
central dopaminergic effect on
decreasing peripheral sympathetic tone
decreasing insulin resistance
Decreases CV outcomes 50% in 1 year
Colsevelam- drop 0.5%
lipid benefit
(Ranolazine) drop %
Decrease angina ( or equivalent)
Decreases arrhythmia
Improves diastolic dysfunction, thus-decreases edema of Pio-,
Decreases HgA1c, FBS in glucose dependent fashion , no hypoglycemia

7. SCN Uses DOPAMINE The Biologic Clock Integrator of Signals ADAPTIVE IR
Summer/ AM
Winter/ overnight
High Dopa Set
Low IR
Low
Sym-
pathetic
tone
Low Dopa Set
High IR
High Sympathetic tone
Persistent
Maladaptive IR
Hyperglycemia,
high fat/sugar diets,
altered sleep/wake cycles,
no exercise, stress
patients with genetically
susceptible b-cell
Diabetes Mellitus

8. Bromocriptine QR: Proposed mechanism of action
Morning administration
(within 2 hours
of waking) of AGENT
Corrects
Low dopaminergic tone in hypothalamus in early morning in diabetes
Restoration of morning peak in dopaminergic activity (via D2 receptor-mediated activity)
Sympathetic tone
HPA axis tone
 Hepatic gluconeogenesis
 FFA and TG
 Insulin resistance
 Inflammation/hypercoagulation
Sympathetic tone
HPA axis tone
 Hepatic gluconeogenesis
 FFA and TG
 Insulin resistance
 Inflammation/hypercoagulation
The central and peripheral dopaminergic system is involved in the regulation of energy homeostasis
Dopaminergic neurotransmission is thought to affect both glucose and lipid metabolism, and in patients with diabetes there is an early morning dip in hypothalamic dopaminergic tone which leads to an increase in sympathetic tone, activation of the hypothalamic-pituitary-adrenal axis, and potentiates systemic low-grade inflammation. These actions precipitate abnormalities in glucose metabolism, insulin resistance and cardiovascular pathology.
When administered within 2 hours of waking, CYCLOSET is thought to restore the dopaminergic activity via its D2-mediated action, improving postprandial glucose (at each of the three standard meals of the day) without increasing insulin secretion. It also reduces triglycerides and free fatty acids.
Decreased postprandial glucose levels
Reduction in insulin resistance
Day-long reduction in plasma glucose, TGs and FFAs
Impaired glucose metabolism, hyperglycemia and insulin resistance
Adverse cardiovascular pathology
Fonseca. Use of Dopamine agonists in Type-2-Diabetes. Oxford American Pocket Cards. OUP, 2010
Cincotta. Hypothalamic role in Insulin Resistance and insulin Resistance Syndrome. Frontiers in Animal Diabetes Research Series. Taylor and Francis, Eds Hansen, B Shafrir, E London, pp , 2002
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9. Therapy for Type II Diabetes9

10. Targets for Glycemic Control
A1C (%)
Normal: 4-6%
Fasting/Preprandial (mg/dL) (plasma equivalent)
Postprandial (mg/dL) (2-hour)
ACE
<6.5
<110
<140
ADA
<7.0
90-130
<180*
* Peak
MANDATORY
Presenter reviews targets for glycemic control as established by the American Diabetes Association and the American College of Endocrinology.
Goals for individual patients may vary.
Aim for the Lowest A1C Possible without Hypoglycemia.
American Diabetes Association. Clinical Practice Recommendations. Diabetes Care. 2004,27:S15-S35
The American Association of Clinical Endocrinologists. Medical Guidelines for the Management of Diabetes Mellitus. Endocr Pract. 2002; 8(Suppl. 1): 40-82 10

11. Inc PPG increases Micro- and macro- vascular disease
Thus , to get to glycemic goals, one must control PPG as well as FBS.
(incretins, alpha-glucosidase inhibitors, TZDs)

12. Reduce Variability and Prevent Build-up of Metabolic Memory
Augers for Avoiding Step-Care Therapy; use Early CombinationTherapy