1. Pramlintide Therapy Part 1of 2
Pharmacodynamic Review
Type 1 Diabetes
Efficacy
Safety

2. Pramlintide: Absolute and Percent Change in Weight
“Evaluable Population”
Absolute Change in Weight (kg)
Percent Change in Weight
Dose Esc
No Drug Follow-up
Dose Esc
No Drug Follow-up
Maintenance
Maintenance
3.5 kg
3.6% * * * *
Pramlintide: Absolute and Percent Change in Weight
Pramlintide is a related drug for the treatment of type 1 and type 2 diabetes that is being developed as an obesity treatment. In its phase 2 trial, individuals, who were not diabetic patients, experienced a 3.5 kg reduction in body weight using this injectible compound in various doses without behavioral intervention over a 16-week period. Therefore, the compound alone was able to achieve weight loss in this situation. Much more research on pramlintide needs to be completed to assure that these results are repeatable and consistent.
Reference:
Weyer C, Aronne L, Fujioka K, et al. Safety, dose-tolerance, and weight-related effects of pramlintide in obese subjects with or without type 2 diabetes. Obes Rev. 2005;6(Suppl 1):21. Abstract O050. † † * * * *
*P<0.0001
†P<.001
*P<0.0001
†P<.001 * * 2 4 8 12 16 24 2 4 8 12 16 24
Time (wk)
Time (wk)
Placebo (n=48)
Pramlintide (n=97)
Weyer C, et al. Obes Rev. 2005;6(Suppl 1):21. Abstract O050.

3. Summary of Pramlintide Effects Type 1, Recommended Dose
HbA1c
Placebo + Insulin (n=393)*
Pramlintide + Insulin (496)*
-0.1
-0.2
-0.3
Mean (SE) Change in HbA1c
-0.4
-0.5
-0.6
-0.7 13 26 39 52
Time (Weeks)
100
Overall Nausea
Severe Hypoglycemia 90 80 70 5 60
Incidence 4 50
(%)
Event 40
Rate/ 3 30
Subject 2 20
Year 10 1
0-4
4-26
26-52
0-4
4-26
26-52
Time (Weeks)
Time (Weeks)
* Evaluable Population

4. Pramlintide Phase 3 Studies Type 1 Diabetes HbA1c Effect for Total Population (ITT, 6 months)
(US)
(Eur)
(US)
+0.1
Pbo + Insulin
30/60QID + Ins
90BID + Ins
60TID + Ins
90TID + Ins
Pbo + Insulin
60TID + Ins
60QID + Ins
n=147
Pbo + Insulin
n=147
-0.1
n=144
n=154
n=234
-0.2
n=148
n=161
Mean (SE) D HbA1c (%)
-0.3
P=0.007
n=164
-0.4
n=243
P=0.013
-0.5
-0.6
P<0.001
Dosage Recommendation: Initiate at 30 µg 3-4 times/day Maintenance 30 or 60 µg 3-4 times/day

5. Addition of Pramlintide to Insulin Reduces HbA1c in Type 1 Diabetes
ITT
Stable Insulin
Placebo + Insulin n=154
Pram 60 TID + Insulin n=164
Pram 60 QID + Insulin n=161
P=0.011
P=0.001
-1.2 -1
-0.8
-0.6
-0.4
-0.2
0.2 13 26 39 52
Weeks
P=0.012
Mean HbA1c Change from Baseline (%)
Weeks
-1.2 -1
-0.8
-0.6
-0.4
-0.2
0.2
P=0.015
P=0.003
P=0.007
P=0.017
HbA1c Change from Baseline (%) 13 26 39 52
Placebo + Insulin n=36
Pram 60 TID + Insulin n=30
Pram 60 QID + Insulin n=30
Mean (SE)
Placebo + Insulin
Pram 60 TID + Insulin
Pram 60 QID + Insulin

6. Pramlintide Therapy Results in Greater Reduction in HbA1c Than Insulin Alone in Type 1 Diabetes, Recommended Doses (Week 26)
Worse
Improved
100 90 10 80 20 70 30 60 40
Cumulative Percent 
Cumulative Percent  50 50 40 60 30 70 20 80 10 90
100 -2
-1.5 -1
0.5
0.5 1
1.5 2
Change in HbA
(%) From Baseline 1C
Placebo
Pramlintide 30/60 QID
Pramlintide 60 TID
Pramlintide 60 QID

7. Pramlintide Facilitates Achievement of ADA Targets Type 1 Diabetes, Week 26
Placebo + Insulin
Pramlintide
Recommended Doses
Achieved 8% or Less
Achieved 7% or Less
28% 7%
47%
14%
Pooled data

8. Weight Effect Type 1 Diabetes, Week 26
(US)
(Eur)
(US)
Pbo + Insulin
30/60QID + Ins
Pbo + Insulin
90BID + Ins
60TID + Ins
90TID + Ins
Pbo + Insulin
60TID + Ins
60QID + Ins 3 2 1
n=168
n=104
Mean (SE) D Weight (lb)
n=119 -1
n=86
n=174
n=106
n=99 -2
P=0.0035 *
n=113
n=90 -3
P<0.0001 *
P<0.0001 * -4
P<0.0001 *
P<0.0001 *
P<0.0001 * -5

9. Adverse Event Profile for Type 1 Diabetes using Pramlintide Frequent TEAEs (% of Subjects), Overall Incidence > 5%, Excluding Hypoglycemia
Placebo N=538
Pramlintide N=1179
Nausea Anorexia Vomiting Abdominal pain Fatigue Dizziness Dyspepsia
17 (1 severe)
51 (7 severe)