Transcript Therapy of Type 2 Diabetes Mellitus, Update, Part 9

Therapy of Type 2 Diabetes
Mellitus: UPDATE
Glycemic Goals in the Care of Patients with Type
2 Diabetes- 2013 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
Approach to management
of hyperglycemia:
more
stringent
Figure 1
Strongly
disagree with
less stringent
less motivated, non-adherent,
Advicepoor self-care capacities
less
stringent
Patient attitude and
expected treatment efforts
highly motivated, adherent,
excellent self-care capacities
Risks potentially associated
with hypoglycemia, other
adverse events
low
Disease duration
newly diagnosed
Life expectancy
long
Important comorbidities
absent
few / mild
severe
Established vascular
complications
absent
few / mild
severe
Resources, support system
readily available
high
long-standing
short
limited
ie: I would
be as
aggressive
in care as
other
Patients,
as
long as don’t
use agents
that cause
weight gain o
hypoglycemia
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)
2
AACE/ACE: Recommendations Based on A1C at
Diagnosis
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
Triple therapy
AACE: American Association of Clinical Endocrinologists
A1C > 9.0%
Triple therapy
If drug
naive
Insulin plus
other
agent(s)*
NO SU, EARLY COMBO,
FIRST/SECOND TIER AGENTS
Rodbard HW, et al. Endocr Pract. 2009;15:540-559.
Pick Right Drug for Right Patient and Vice Versa: next slide
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
Conventional Therapy,
8.6 to 6.1% at 6 mo and remained stable at 6.1% at 24
6.1% 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%
Triple Therapy subjects had a 13.6-fold lower rate of
compared to subjects receiving Conventional Therapy.
Triple Therapy subjects had mean weight
in subjects on Conventional Therapy.
(46 vs 22%, p<0.0001).,
hypoglycemia
loss of 1.2 kg versus 3.6 kg weight gain
(p=0.02)
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.
6
My Own Views
1. 3-4 non-insulin agents before consider insulin
1. Not SU/GLINIDE
2. AACE first Tier/ Second Tier Principle
3. Beta cell- incretin/SGLT-2 Inh/ Pio
4. Resistance- Pio/ metformin
5. 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
Weight Reduction Issues
1. GLP-1’s In Metabolic Syndrome2. 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
SGLT-2 Inhibitor with Incretins
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
10
Alternatives for the Use of Nearly Physiological Insulins
and Non-Insulin Therapy
X
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
Alternatives for the Use of Nearly
Physiological Insulins
Planning Insulin Therapy with the Patient
SOME
MDI
fast analog
basal
or
Pump
MANY
Basal incretin SGLT2+TZDmetformin
x
Practical
x
x
Premixed
Nph/Fast-analog
or
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
David Kendall