Transcript The Pyramid of Recent Trials

Pramlintide Therapy
Part 2 of 2
 Pharmacodynamic Review
 Type 1 Diabetes
Efficacy
Safety
Severe Hypoglycemia Annual Event
Rate by Dose
Type 1 Diabetes
Weeks 0-4
5
4
Mean (SE)
3
Event
Rate Per
Subject
2
Year
1
0
Placebo
+ Ins
Pram 30 QID
+ Ins
Pram 60 TID
+ Ins
Pram 60 QID
+ Ins
Pram 90 BID
+ Ins
Pram 90 TID
+ Ins
Risk for Severe Hypoglycemia
Decreases over Time
Type 1 Diabetes, All Patients
0.06
Placebo + Insulin
Pramlintide + Insulin
0.05
Risk
0.04
0.03
0.02
0.01
0.00
2
4
6
8
10
12
14
16
RT O’Neill Drug Information Journal; 21: 9-20, 1987.
18
20
22
24
26
28
30
Weeks
32
34
36
38
40
42
44
46
48
50
52
Pramlintide Benefits are Seen in Patients with
Type 1 Diabetes Targeting Optimal Glycemic Control
8
Mean
HbA1C
(%)
7.8
7.6
7.4
7.2
4
6
8
Time (Weeks)
4.5
Weight
Insulin Use
6
4
2
0
10 12 14 16 18 20 22 24 26
1
0
-1
-2
-3
Event Rate Per Subject Year
2
Change in Weight (lb)
Change in Insulin Use (%)
0
4.0
3.5
3.0
2.5
2.0
1.5
1.0
0.5
0
Pramlintide (n=243)
Placebo (n=173)
Severe Hypoglycemia
Weeks
0-4
Weeks
4-26
Other Safety Observations
Type 1 Diabetes
 No evidence of:
– Serious events that are unusual in the absence
of drug therapy
– Cardiac toxicity
– Hepatic toxicity
– Renal toxicity
 No increase in frequency of clinically significant:
– Lipid abnormalities
– ECG changes
– Changes in vital signs
Systolic blood pressure
 Diastolic blood pressure
– Laboratory abnormalities

Pramlintide is Efficacious and Safe
in Type 1 Diabetes
 Improves glycemic control
 Weight loss
 Increased insulin-induced hypoglycemia only
during initiation of therapy
– No increase in insulin-induced hypoglycemia after
initiation of therapy
 No other safety issues
 Dosage recommendation:
– Initiate at 30 µg 3-4 times/day before meals
– Maintenance 30 or 60 µg 3-4 times/day before meals
Guidelines for Initiation of
Therapy
 Initial Dose
– Type 2: 120 µg
– Type 1: 30 µg or lower
 Dose Frequency
– Determined by meal pattern
– Administered within 15 minutes before a
meal
 Insulin Reduction
– 10%-20% of preprandial, short-acting insulin
dose
For use with meal time insulin
Pramlintide
Approved for those using insulin and not at goal

Used only with insulin to lower BG after meals

Only given at mealtimes

Increases risk for Hypoglycemia

Patient must check before/after meals and bedtime

Rapid insulin dose reduced 50%

Will help lose weight

Most common side effect is Nausea-dose related

Cannot mix with insulin

Must be titrated to lessen nausea

Starting dose 15micrograms increasing gradually to a max of
120ug

Must not use if eating less then 250 calories or 30gm carbs

No driving until regulated

Reduces caloric intake, delays food adsorbtion lowering PPBG
and reduces Glucagon secretion.