Transcript No Slide Title

Basal Bolus: The Strategy for
Managing All Diabetes
Fall, 2003
Paul Davidson, MD, FACE
Atlanta Diabetes Associates
Atlanta, Georgia
ACE / AACE Targets for Glycemic Control
HbA1c
< 6.5 %
Fasting/preprandial glucose
< 110 mg/dL
Postprandial glucose
< 140 mg/dL
ACE / AACE Consensus Conference, Washington DC August 2001
Step Therapy
 Diet
 Exercise
 Sulfonylurea or Metformin
 Add Alternate Agent
 Add hs NPH
 Switch to Mixed Insulin bid
 Switch to Multiple Dose Insulin
Utilitarian, Common Sense, Recommended
Prone to Failure from
Misscheduling and Mismanagement
Stumble Therapy
 YAG Diet
 Golf Cart Exercise
 Sample of the Week Medication
– Interupted,
– Not Combined
 Poor Understanding of Goals
 Poor Monitoring
HbA1c >8% (If Seen)
Informed Patient Refers Self Elsewhere
PETS Therapy
Step--Spelled Backwards
All at once, nothing first,
Just like bubbles, when they burst.
 Start with Fast to Glucose <126 mg/dL
– Glargine, Wt x 0.1 units qd
 Feed PSMF Diet
 Add SU, MF, TZD, Repaglanide + prn Lispro for BG
<150
 “Normal” BG from Day 1
 Monitor BG qid
 See Patient Monthly, HFP
 HbA1c Bimonthly
GI Problems: Cut MF
Hypoglycemia: Cut SU
Hypoglycemia Again: Cut Repaglinide
Allow 2 Month to See TZD Effect
MIMICKING NATURE
WITH INSULIN THERAPY
All persons need
both basal and mealtime insulin
to control glucose
(endogenous or exogenous)
6-19
Limitations of NPH, Lente,
and Ultralente
 Do not mimic basal insulin profile
– Variable absorption
– Pronounced peaks
– Less than 24-hour duration of action
 Cause unpredictable hypoglycemia
– Major factor limiting insulin adjustments
– More weight gain
Insulin Glargine
A New Long-Acting Insulin Analog
 Modifications to human insulin chain
– Substitution of glycine at position A21
– Addition of 2 arginines at position B30
 Gradual release from injection site
 Peakless, long-lasting insulin profile
Gly
1
5
10
15
20Asp
1
5
10
15
20
Substitution
25
30
Extension
Arg Arg
Glucose Infusion Rate
SC insulin
n = 20 T1DM
Mean ± SEM
4.0
24
mg/kg/min
3.0
16
Ultralente
12
2.0
8
CSII
1.0
4
Glargine
0
NPH
0
4
8
12
Time (hours)
Lepore M, et al. Diabetes. 2000;49:2142–2148.
16
20
0
24
µmol/kg/min
20
Glargine vs NPH Insulin in Type 1 Diabetes
Action Profiles by Glucose Clamp
Glucose utilization rate
(mg/kg/h)
6
NPH
Glargine
5
4
3
2
1
0
0
10
20
30
Time (h) after SC injection
End of observation period
Lepore, et al. Diabetes. 1999;48(suppl 1):A97.
Treat to Target Study: NPH vs
Glargine in DM2 patients on OHA
 Add 10 units Basal insulin at bedtime
(NPH
or Glargine)
 Continue current oral agents
 Titrate insulin weekly to fasting BG < 100 mg/dL
• Based on average FBG of 6th and 7th day
- if 100-120 mg/dL, increase 2 units
- if 120-140 mg/dL, increase 4 units
- if 140-160 mg/dL, increase 6 units
- if 160-180 mg/dL, increase 8 units
The Treat-to-Target Trial
Randomized addition of glargine or human NPH insulin to oral therapy of type 2 diabetic patients
Riddle, Rosenstock, Gerich
DIABETES CARE 2003 26;3080-2083
The Treat-to-Target Trial
Randomized addition of glargine or human NPH insulin to oral therapy of type 2 diabetic patients
Riddle, Rosenstock, Gerich
DIABETES CARE 2003 26;3080-2083
70
66.2
58
60
48.8
50
40
32.3
30
20
10
2.5
0
Week 0
Week 8
Week 12
Week 18
Week 24
Percentage of Patients in Target (A1C < 7%)
GEMS--Glargine Evening
Mealtime Secretagogue
 Basal Dosing
– (Weight in #`s x 0.1)
• Glargine hs
 Prior to Meals
– Short Acting Secretagogue
• Rapaglinide 2 mg
• Nateglinide 120 mg
– Glimepiride 2 mg
The Treat-to-Target Trial
Randomized addition of glargine or human NPH insulin to oral therapy of type 2 diabetic
patients
Riddle, Rosenstock, Gerich
26;3080-2083
DIABETES CARE 2003
The Treat-to-Target Trial
Randomized addition of glargine or human NPH insulin to oral therapy of type 2 diabetic patients
Riddle, Rosenstock, Gerich
DIABETES CARE 2003 26;3080-2083
The Treat-to-Target Trial
.
Bedtime Glargine vs NPH
With Mealtime Regular
48
4
Glargine
NPH
36
Weight (kg)
**
2
24
1
12
Patients (%)
3
*
0
Weight Gain
*P < .0007
**P < .02 (compared to NPH)
Nocturnal
Hypoglycemia
0
Rosenstock, et al. Diabetes. 1999;48(suppl 1):A100.
6-52
Treatment to Target Study: NPH vs
Glargine in DM2 patients on OHA
 57% had HbA1c <7%
 Nocturnal Hypoglycemia reduced by 42% in
the Glargine group
 33% had HbA1c <7% without any nighttime
hypoglycemia in glargine group
 Results significantly better than with NPH
Establishing Basal Requirement for Glargine
Body Weight in pounds x 0.1
Average am BG x 2 after five days
Add to Glargine (BG-100)/10
Repeat weekly
Example: 200#
20 units glargine q hs
AM BG averages 200 on 6th and 7th day
Add (BG-100)10 to glargine,
i.e. increase to 20 to 30 units q hs
2nd week--average 130
increase glargine from 30 to 33
Overall Summary: Glargine
 Insulin glargine has the following
clinical benefits
– Once-daily dosing because of its prolonged duration of
action and smooth, peakless time-action profile
– Comparable or better glycemic control (FBG)
– Lower risk of nocturnal hypoglycemic events
– Safety profile similar to that of human insulin