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 9 1

2. weight gain or hypoglycemia
Strongly
disagree with
less stringent
Advice-
ie: I would
be as
aggressive
in care as
other
Patients, as
long as don’t
use agents
that cause
weight gain or hypoglycemia
Depiction of the elements of decision-making used to determine appropriate efforts to achieve glycaemic targets. Greater concerns about a particular domain are represented by increasing height of the ramp. Thus, characteristics/predicaments towards the left justify more stringent efforts to lower HbA1c, whereas those towards the right are compatible with less stringent efforts. Where possible, such decisions should be made in conjunction with the patient, reflecting his or her preferences, needs and values. This ‘scale’ is not designed to be applied rigidly but to be used as a broad construct to help guide clinical decisions. Adapted with permission from Ismail-Beigi et al [ref 20]
Figure 1
Diabetes Care, Diabetologia. 19 April 2012 [Epub ahead of print]
(Adapted with permission from: Ismail-Beigi F, et al. Ann Intern Med 2011;154:554)

3. AACE/ACE: Recommendations Based on A1C at Diagnosis
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
NO SU, EARLY COMBO,
FIRST/SECOND TIER AGENTS
AACE: American Association of Clinical Endocrinologists
Rodbard HW, et al. Endocr Pract. 2009;15: 3

4. Pick Right Drug for Right Patient and Vice Versa: next slide

6. Initial Triple Combination Therapy is Superior to Stepwise Add-On ConventionalTherapy in Newly Diagnosed T2DM; RALPH A. DEFRONZO,
147 newly diagnosed T2DM (age = 45±1; BMI=36±0.5; A1c = 8.6±0.1%; diabetes duration = 5.6±0.5mo) were randomized to receive initial combination therapy with metformin + pioglitazone + exenatide (Triple Therapy, n=71) or escalating dose of metformin followed by sequential addition of glipizide (5→20 mg/d) and then basal insulin to maintain A1c < 6.5% (Conventional Therapy, n= 76). Results: Triple Therapy, A1c to 6.1% at 6 mo and remained stable at 6.1% at 24 Conventional Therapy, % at 6 mo and then increased to 6.6% at 24 mo (p < 0.01). More subjects in Conventional Arm failed to achieve the treatment A1c goal <6.5% (46 vs 22%, p<0.0001)., Triple Therapy subjects had a 13.6-fold lower rate of hypoglycemia compared to subjects receiving Conventional Therapy. Triple Therapy subjects had mean weight loss of 1.2 kg versus 3.6 kg weight gain (p=0.02) in subjects on Conventional Therapy. Conclusion: Antidiabetic therapy targeting the core metabolic defects (insulin resistance and beta cell dysfunction) responsible for hyperglycemia is more effective and safer than therapy simply aimed at lowering the plasma glucose conc without correcting the underlying pathophysiologic disturbances present in T2DM.

7. My Own Views 3-4 non-insulin agents before consider insulin
Not SU/GLINIDE
AACE first Tier/ Second Tier Principle
Beta cell- incretin/SGLT-2 Inh/ Pio
Resistance- Pio/ metformin
Other- bromocriptine-QR, colsevalam
2. Insulin only if following NCS diet (otherwise a set up for wt. gain/ hypoglycemia
3. Keep Non-Insulin treatments as start basal- if do so only ~10% need bolus
4. If on insulin, can decrease 25% if not following diet; dec 25% if getting low
dec. 25 % if start canagloflozin, dec 20% if starting GLP-1 RA

8. Weight Reduction Issues
1. GLP-1’s In Metabolic Syndrome-
2. Incretins Before Pioglitazone
3. GLP-1 RA’s preferred over DPP-4 in ‘right patient’
4. GLP-1 RA’s/ SGLT-2 Inhibitors may have additive wt. reduction
5. GLP-1 RA’s/ SGLT-2 Inhibitor always before go to Insulin, even a short trial
6. Unless ‘sick’, avoid insulin if not following NCS diet
7. Keep on Incretin/ SGLT-2 Inhibitor when add insulin.
8. If on insulin, decrease 25% as start NCS diet
decrease 25% if was having hypoglycemia
add pioglitazone, metformin, if possible
add incretin , GLP-1 preferred; add SGLT-2 inhibitor
May be able to stop insulin, lose weight
Schwartz, Fabricatore, Diamond, Weight Reduction in Diabetes, Book Chapter “Diabetes: An Old Disease, a New Insight,” edited by Dr. Ahmad., Landes Bioscience, 2011

9. SGLT-2 Inhibitor with Incretins

10. 1.NO NEED FOR EARLY INSULIN THERAPY ANYMORE TO DECREASE LIPO/GLUCOTOXICITY – CAN DO WITH INCRETIN INCRETIN
2. DON’T START IF EATING WRONG DIET- AVOID WT. GAIN/ HYPO/ REBOUND STORY- VICIOUS CYCLE
3. DELAY UNTIL 3-4 DRUG FAILURE, on DIET

11. Alternatives for the Use of Nearly Physiological Insulins and Non-Insulin TherapyX
RARE
Type 2- ~80% need basal; if on dpp-4=50%,on GLP-1 RA=30%, SGLT-2 inh= 30%
on Incretin/ SGLT-2 only~ 10%
Type 1- Pumps in many- eg: with variability/hypo’s, dawn effect
now pump need rare: if on incretin or SGLT-2 Inh. Or Both
Main Pump indication now is gastroparesis where need dual square waves

12. Alternatives for the Use of Nearly Physiological Insulins
Planning Insulin Therapy with the Patient x
SOME
MANY
Practical x
MDI fast analog basal
Basal incretin SGLT-2+TZDmetformin
Premixed Nph/Fast-analog or or x
Pump
Glarginenon-insulin Rx+
1-2 doses fast analog
Self-mixed
NPH
fast analog
incretins with basal insulin obviates need for bolus therapy in many patients

13. David Kendall