1. 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

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. 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

4. 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

5. Pramlintide (n=243) Placebo (n=173) Time (Weeks) Insulin Use Weight
Pramlintide Benefits are Seen in Patients with Type 1 Diabetes Targeting Optimal Glycemic Control 8
7.8
Mean HbA1C (%)
7.6
7.4
7.2
Pramlintide (n=243)
Placebo (n=173) 2 4 6 8 10 12 14 16 18 20 22 24 26
Time (Weeks) 2 4 6
Change in Insulin Use (%)
Insulin Use
Change in Weight (lb) -3 -2 -1 1
Weight
Severe Hypoglycemia
4.5
4.0
3.5
3.0
Event Rate Per Subject Year
2.5
2.0
1.5
1.0
0.5
Weeks 0-4
Weeks 4-26

6. 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

7. 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

8. SYMLIN Boxed Warning DISCUSSION POINTS: SLIDE BACKGROUND:
Symlin_PI_and_Med_Guide2005_p1.pdf