1. Pramlintide Synthetic analog of the β-cell hormone amylin
Limits postprandial glucose excursions through at least three mechanisms of action
Slows gastric emptying
Decreases postprandial hypersecretion of glucagon
Increases satiety, leading to decreased food intake and potential weight loss
In long term clinical trials pramlintide, as an adjunct to mealtime insulin in patients with type 2 and type 1 diabetes, significantly reduced postprandial glucose excursions, A1C, weight and insulin dose
DISCUSSION POINTS:
Pramlintide limits postprandial glucose concentrations, A1C, weight, and insulin use by slowing gastric emptying, reducing inappropriate postprandial glucagon secretion, and increasing satiety
Young. Amylin: Physiology and pharmacology 2005; Edelman, et al. Int J Clin Pract 2006; 60:

2. Summary of Pramlintide Effects Type 1, Recommended Dose
HbA1c
-0.1
Placebo + Insulin (n=393)*
-0.2
-0.3
Mean (SE) Change in HbA1c
-0.4
-0.5
Pramlintide + Insulin (496)*
-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

3. 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
P=0.012 *
-0.6
P<0.001 *
Dosage Recommendation: Initiate at 30 µg 3-4 times/day Maintenance 30 or 60 µg 3-4 times/day

4. 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

5. 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

6. 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

7. Adverse Event Profile for Type 1 Diabetes 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)

8. Risk for Severe Hypoglycemia Decreases over Time Type 1 Diabetes, All Patients
0.06
Placebo + Insulin
Pramlintide + Insulin
0.05
0.04
Risk
0.03
0.02
0.01
0.00 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50 52
Weeks
RT O’Neill Drug Information Journal; 21: 9-20, 1987.

9. 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
Placebo
+ Ins
Pram 30 QID
+ Ins
Pram 60 TID
+ Ins
Pram 60 QID
+ Ins
Pram 90 BID
+ Ins
Pram 90 TID
+ Ins