Transcript Diabetes Mellitus 101 for Cardiologists, Part 16

Diabetes Mellitus 101 for
Cardiologists (and Alike): 2015
An Aggressive Pathophysiologic Approach to Therapy of Type 2 Diabetes
in Cardiometabolic Patients:
Looking at Diabetes Medications with a Cardiologists Eye
Part 16
Stan Schwartz MD,FACP
Affiliate, Main Line Health System
Emeritus, Clinical Associate Professor of Medicine,
U of Pa.
6105472000
New ADA Guidelines- 4/20/12
SU
Still
Prominent
But Incretins
including
DPP-4s
on list
Inzucchi, Diabetes Care
2012;35:1364
Inzucchi,
Diabetologia
4/20/12
Approach to management
of hyperglycemia:
more
less
stringent
stringent
Figure 1
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
less motivated, non-adherent,
poor self-care capacities
high
long-standing
short
limited
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 o
hypoglycemi
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)
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%
If under
treatment
Monotherapy
Dual therapy
Insulin plus
other
agent(s)*
Dual therapy
A1C > 9.0%
If drug
naive
Triple therapy
Triple therapy
Insulin plus
other
agent(s)*
Use Sulfonylureas/Glinides LAST, IF AT ALL
Triple therapy
Therapeutic Choice, based on Safety/ Efficacy,
Should Match The Drug Characteristics With Patient Characteristics
Rodbard HW, et al. Endocr Pract. 2009;15:540-559.
Follow current AACE GUIDELINE
PRINCIPLES
 Treat as many of the Ominous Octet Targets as needed, with least # of
agents, to get lowest sugars/HgA1c as possible without undue weight
gain or hypoglycemia
 Early Combination Therapy
First Tier- Efficacy, (my add- CV event reduction, Weight Loss)
 Treat with agents that address FBS AND PPG
 Ideally agents will stabilize, preserve beta-cells , the CORE DEFECT (
NO SU/GLINIDES)
 Ideally agents will have potential to synergistically decrease in CV risk
factors/ outcomes
Initial Triple Combination Therapy
is Superior to ADA Guide
147 newly diagnosed T2DM
(age = 45±1; BMI=36±0.5; A1c = 8.6±0.1%; diabetes duration = 5.6±0.5mo) were randomized
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% (46 vs 22%, p<0
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.
First Tier/ Second Tier AACE Meds
 First Tier- drop HgA1c 1-2%
 Metformin,
pioglitazone , GLP-1 RA
 Second Tier

SGLT-2 inh.
 DPP-4
Inh, ranolazine,
 bromocriptine-QR,
inh.
colsevalam, alpha-glucosidase
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
Concurrent Therapy
Aggressive medical therapy in diabetes
ACE inhibitors
ARBs
β-blockers
CCBs
Diuretics
Hypertension
Statins
Fibric acid derivatives
Colsevalam
Dyslipidemia
Atherosclerosis
Metformin
TZDs
Sulfonylureas/Glinide
RANOLAZINE
colsevalam
Hyperglycemia/
Insulin resistance
Incretins
Insulin
ASA
Clopidogrel
Ticlopidine
Platelet activation
and aggregation
Adapted from Beckman JA et al. JAMA. 2002;287:2570-81.
Treating the ABCs Reduces
Diabetic Complications
Strategy
Blood glucose control
Blood pressure control
Lipid control
1 UKPDS
Complication
▪ Heart attack
 37%1
▪ Cardiovascular disease
 51%2
▪ Heart failure
 56%3
▪ Stroke
 44%3
▪ Diabetes-related deaths
 32%3
▪ Coronary heart disease mortality
35%4
▪ Major coronary heart disease event
55%5
▪ Any atherosclerotic event
37%5
▪ Cerebrovascular disease event
53%4
Study Group (UKPDS 33). Lancet. 1998;352:837-853.
L, et al. Lancet. 1998;351:1755-1762.
3 UKPDS Study Group (UKPDS 38). BMJ. 1998;317:703-713.
4 Grover SA, et al. Circulation. 2000;102:722-727.
5 Pyŏrälä K, et al. Diabetes Care. 1997;20:614-620.
2 Hansson
Reduction of
Complication
Synergies In Therapy for the Cardiometabolic
Syndrome
?√
Summary
 Treat aggressively-benefit on cost and complications
 Treat elements of pathophysiology

Resistance-glycemia,endothelial
dysfunction,lipids,BP,coag.

Secretion-first phase,incretin,importance of PPG

Multi-hormonal issues

Use SIDE-BENEFITS of the various agents
 Treat to new goals using combinations that make
pathophysiologic sense
 Guidelines should help pick right drug(s) for right patients