Transcript Hyperglycemia and acute coronary syndromes

Practical
Considerations in
Clinical Management
Guideline-recommended glycemic targets
in diabetes
A1C
(%)
FPG
(mg/dL)
Postprandial
glucose
(mg/dL)
ADA
<7
90-130
<180*
ACE
≤6.5
<110
<140†
*Plasma; †Blood
ADA = American Diabetes Association
ACE = American College of Endocrinology
ADA. Diabetes Care. 2007;30(suppl 1):S4-41.
ACE. Endocr Pract. 2002;8(suppl 1):5-11.
Glucose dynamics: Basal and prandial
250
Postprandial hyperglycemia
200
Plasma
glucose
(mg/dL)
Type 2
diabetes
150
Basal hyperglycemia
100
50
Normal
0
0600
1200
1800
2400
0600
Time of day
Riddle MC. Am J Med.
2004;116(suppl):3S-9.
Relative contributions of postprandial glucose
and FPG to A1C
100
80
Contribution
(%)
60
40
20
0
<7.3
7.3–8.4
8.5–9.2
9.3–10.2
>10.2
A1C quintiles (%)
Fasting plasma glucose
Postprandial plasma glucose
Monnier L et al. Diabetes Care. 2003;26:881-5.
Glycemic control deteriorates with standard
therapies
N = 2220 with T2DM treated with SU + MET
Pre-SU A1C levels (%)
≥10
9.0-9.9
8.0-8.9
4.0-7.9
100
80
Patients 60
with
A1C ≥8%
40
(%)
~85% of patients
had A1C ≥8%
after 4 years
20
0
0
1
2
3
4
Time from sulfonylurea initiation (years)
SU = sulfonylurea, MET = metformin
Cook MN et al. Diabetes Care. 2005;28:995-1000.
A1C reduction with glucose-lowering
medications
Oral agents
Sulfonylureas
Biguanides (metformin)
Glinides
Thiazolidinediones
DPP-IV inhibitors
α-Glucosidase inhibitors
A1C (%)*
1.5
1.5
1.0–1.5
0.8–1.0
0.5–0.9
0.5–0.8
Parenteral/inhaled agents
Insulin
Inhaled insulin
GLP analogues
Amylin analogues
≥2.5
1.5
0.6
0.6
*Monotherapy
DPP = dipeptidyl peptidase; GLP = glucagon-like peptide
Nathan DM. N Engl J Med. 2007;356:437-40.
Oral diabetes agents
Drug class
Agent(s)
Mechanism(s) of action
α-Glucosidase
inhibitors
Acarbose, miglitol
Delay carbohydrate absorption
Biguanides
Metformin
Hepatic glucose production
Insulin sensitivity in liver + muscle
Sulfonylureas
Glimepiride,
glipizide, glyburide
Insulin secretion from pancreatic  cells
Meglitinides
Nateglinide,
repaglinide
Insulin secretion from pancreatic  cells
Thiazolidinediones
Pioglitazone,
rosiglitazone
Insulin sensitivity in fat cells + muscle
DPP-IV inhibitors
Sitagliptin, vildagliptin
(Phase III)
GLP-1 degradation; Glucosedependent insulin secretion
Trujillo J. Formulary. 2006.
Luna B, Feinglos MN. Am Fam Physician. 2001.
Smyth S, Heron A. Nat Med. 2006.
Incretin agents in glucose control
DPP-IV inhibitors
Incretin mimetics
• Significant A1C
•
• Weight neutral
• Weight loss
• Oral administration
• Injection
• Almost no GI side effects
• Higher rate of GI side effects
• Very low rate of hypoglycemia
• Low rate of hypoglycemia
• Multiple targets (GLP-1 and GIP)
• Single target (GLP-1)
GIP = gastric inhibitory peptide
Significant A1C
Trujillo J. Formulary. 2006;41:130-41.
ADA: Managing hyperglycemia in T2DM
Lifestyle intervention + metformin
If A1C > goal
Add basal insulin
(most effective)
Add sulfonylurea
(least expensive)
Add glitazone
(no hypoglycemia)
If A1C > goal
If A1C > goal
If A1C > goal
Intensify insulin
Add glitazone
Add basal insulin
If A1C > goal
Add sulfonylurea
If A1C > goal
Add basal or intensify insulin
Intensive insulin + metformin +/- glitazone
ADA goal: A1C <7%
Adapted from ADA. Diabetes Care. 2007;30(Suppl 1):S4-41.
ACE road map to glycemic goals in T2DM:
Treated patients
A1C
(%)
6.5–8.5
6.0–6.5
Continue lifestyle modification
>8.5
Current therapy
Intervention
Mono- or
Initiate insulin therapy
combination therapy (basal-bolus)
Combination
therapy
Maximize OAD combinations
Maximize insulin therapy
Monotherapy
Initiate combination therapy*
Mono- or
combination
therapy
Continue therapy or
adjust as needed to meet
ACE glycemic targets
*Add rapid-acting insulin analogs at any time to
address persistent postprandial hyperglycemia
• Monitor every
2–3 months
• Adjust treatment
to meet ACE
glycemic goals
ACE/AACE. www.aace.com.
Treat-to-Target study: Basal insulin lowers
FPG and A1C
N = 756 previously treated with 1–2 OADs; Mean A1C 8.6%
9
200
FPG,
mean 150
(mg/dL)
A1C,
mean
(%)
8
7
6
100
0
4
8
12
16
20
24
0
4
8
12
16
20
24
Weeks of treatment
~60% reached A1C ≤7%
Insulin glargine
NPH = neutral protamine Hagedorn insulin
NPH
Riddle MC et al. Diabetes Care. 2003;26:3080−6.
Treat-to-Target: Nocturnal hypoglycemia
vs glycemic control
A1C ≤7% (%)
Without nocturnal hypoglycemia (%)
FPG ≤100 mg/dL (%)
Without nocturnal hypoglycemia (%)
Dose, mean (units/day)
Insulin
glargine
(n = 367)
NPH
(n = 389)
58
57
33
27
36
34
22
16
<0.03
47.2
41.8
<0.005
P
<0.05
Riddle MC et al. Diabetes Care.
2003;26:3080―6.
Fewer hypoglycemic episodes with
insulin analogue
N = 371 with poorly controlled T2DM on SU + MET
12
P < 0.0001
10
8
Hypoglycemic
events, mean
(per patient-years)
P = 0.0009
6
4
P = 0.0449
2
0
Total
Symptomatic
Insulin glargine + OAD
*30% regular/70% NPH insulin
Nocturnal
Premixed insulin*
Janka HU et al. Diabetes Care. 2005;28:254-9.
Insulin glargine + OAD effect on weight, A1C
N = 12,216 with poorly controlled T2DM on OAD; 9-month outcomes
1.0
BMI subgroup analysis
0.9
0.0
 BMI
(kg/m2)
-0.3
-0.5
-1.0
-1.3
-2.0
-2.1
-3.0
BMI (kg/m2)
<25
25 to <30
30 to <35
≥35
All
 A1C (%)
-1.6
-1.6
-1.7
-1.8
-1.6
 = change from baseline at 9 months
Schrieber SA, Haak T. Diabetes Obes Metab. 2007;9:31-8.
Glycemic control and weight change with
detemir vs NPH insulin
N = 475 with poorly controlled T2DM on OAD; add-on detemir or NPH
A1C
(%)
10
189
9
187
185
Body
weight 182
(lbs)
180
8
7
6
178
0
0
-2 0
4
8 12 16 20 24
Study week
>70% achieved A1C ≤7%
Detemir
NPH
-2 0
4
8 12 16 20 24
Study week
Mean weight gain (lbs)
Detemir: 2.6; NPH: 6.2
(P < 0.001)
Hermansen K et al. Diabetes Care. 2006;29:1269-74.
Add-on treatment with glargine vs rosiglitazone
+ SU/MET: A1C and FPG
N = 217 with T2DM
7
8
9
10
11
0
200
-0.5
180
†
-1.0
A1C,
 from -1.5
baseline -2.0
(%)
-2.5
*
*
*
*
†
FPG, 160
mean
(mg/dL) 140
†
†
120
-3.0
-3.5
100
0
4
8
12
16
20
24
Time (weeks)
Insulin glargine
*P < 0.05, †P = 0.001 between groups
Rosiglitazone
Rosenstock J et al. Diabetes Care. 2006;29:554-9.
Glargine vs rosiglitazone added to SU + MET:
Lipid effects
N = 217 with T2DM
Total-C
LDL-C
20
†
13.1
*
10.1
10
Change
from
baseline
(%)
HDL-C
TG
‡
§
4.6
4.4
0
0
-1.4
-4.4
-10
-20
-19.0
Insulin glargine
*P = 0.0001, †P = 0.0004, ‡P = 0.001,
§P = 0.04 between groups
Rosiglitazone
Rosenstock J et al. Diabetes Care. 2006;29:554-9.
Add-on Rx with glargine vs rosiglitazone
+ SU/MET: Comparative adverse effects
N = 217 with T2DM
Insulin glargine
(n = 105)
Rosiglitazone
(n = 112)
P
Nocturnal hypoglycemia* (%)
27.6
10.7
0.02
Weight gain (lb)
3.7
6.6
0.02
0
12.5
0.001
6.7
28.6
<0.0001
Peripheral edema (%)
Adverse events (%)
*Plasma glucose <70 mg/dL
Rosenstock J et al. Diabetes Care. 2006;29:554-9.
Bolus
Basal
Basal and bolus insulin pharmacodynamics
Formulation
Coverage
Glargine
Basal
24
Once daily
Detemir
Basal
14
Once or twice daily
NPH
Basal
13
Twice daily
Lispro
Prandial
3–4
≤15 min premeal to
immediately postmeal
Aspart
Prandial
3–4
≤15 min premeal to
immediately postmeal
Glulisine
Prandial
3–4
≤15 min premeal to
≤20 min postmeal
RHI
Prandial
6–8
30 min premeal
RHI = regular human insulin
Duration (hr)
Dosing
Flood TM. J Fam Practice. 2007;56(suppl):S1-12.
Dispelling misconceptions about insulin
Traditional thinking
Newer concepts
• Atherogenic
• Anti-atherogenic
• Fear of hypoglycemia
• Less nocturnal hypoglycemia
with steady-state once-daily
basal insulins
• Fear of weight gain
• Weight neutral
• Frequent injections
• Long-acting basal insulins
require fewer injections
Dandona P et al. Am J Cardiol. 2007;99(suppl):15B-26.
Stotland NL. Insulin. 2006;1:38-45.
ACC/AHA secondary prevention guidelines:
Diabetes management
Class and level of evidence
I IIa IIb III
B
Initiate lifestyle and pharmacotherapy to achieve
A1C <7%
B
Aggressively modify other CV risk factors
(physical activity, weight, BP, cholesterol)
C
Coordinate care with endocrinologist or PCP
Smith SC et al. Circulation. 2006;113:2363-72.
Discharge strategies for patients with
hyperglycemia
Lifestyle modification
(nutrition and exercise)
Insulin vs OAD
for long-term management
Patient education
eg, self-monitoring of glucose
Continuity of care
PCP ± Endocrinologist
ACE/ADA. Diabetes Care. 2006;29:1955-62.
Managing glucose in T2DM
• Diabetes is a progressive disease
• Most patients will require multiple therapies to achieve
A1C goals
• Utilize lifestyle intervention and metformin as initial
treatment
• Add medications rapidly and transition to new agents
when A1C target is not achieved/sustained
• Add insulin early in patients who do not meet A1C
targets
Nathan DM et al. Diabetologia. 2006;49:1711-21.
Continuity of care for diabetes:
It takes a health care team
Patient
Physician
Diabetes
educator
Eye doctor
Dietician
Exercise
physiologist
Podiatrist
Social worker or
psychologist
ADA. www.diabetes.org.