1
Accreditation and
Designation of Credit
The Network for Continuing Medical Education (NCME)
is accredited by the Accreditation Council for
Continuing Medical Education to provide continuing
medical education for physicians.
NCME designates this educational activity for a
maximum of 1 AMA PRA Category 1 Credit™.
Physicians should only claim credit commensurate
with the extent of their participation in the activity.
2
Disclosure Statement
The Network for Continuing Medical Education requires
that CME faculty disclose, during the planning of an
activity, the existence of any personal financial or other
relationships they or their spouses/partners have with
the commercial supporter of the activity or with the
manufacturer of any commercial product or service
discussed in the activity.
3
Faculty Disclosure
Curtis Triplitt, PharmD
Texas Diabetes Institute
Clinical Asst. Professor, Dept.
of Medicine/ Div. of Diabetes,
University of Texas Health Science Center at San Antonio
• Speaker’s Bureau- Amylin/Lilly for Byetta
• Consulting-Consulting Fees- Roche/Johnson &
Johnson/ Novonordisk/ Takeda
4
Learning Objectives
After taking part in this activity, participants should be
able to:
 Recognize that postprandial glucose control involves multiple
glucoregulatory hormones, including the beta-cell hormone
amylin
 Describe the physiologic and clinical benefits of amylinreplacement therapy in insulin-requiring patients
with diabetes
 Identify patients who are candidates for amylin-replacement
therapy, and develop individualized treatment strategies using
this therapy as an adjunct to insulin
5
Limitations of Intensified Insulin Therapy
Added to Oral Therapy: 4-T Trial
Type 2 Diabetes: Metformin + Sulfonylurea Failure
Prandial Insulin (n=239)
Basal Insulin (n=234)
Biphasic Insulin (n=235)
If A1C levels unacceptable on or
after week 24, add second insulin
Add 10 units of long
acting at bedtime
(73.6% of patients)
Add 4-6 units of
preprandial tid
(81.6% of patients)
Add 4-6 units of
preprandial mid-day
(67.7% of patients)
• Target glucose: 72-99 mg/dL preprandial; 90-126 mg/dL at 2 hours postprandial
• Investigators and patients were encouraged to vary suggested insulin doses, as
clinically necessary, and amend the doses between visits
Holman RR, et al. N Engl J Med. 2009;361:1736-1747.
6
Distribution of A1C Levels: 4-T Trial
After 3 Years of Intensified Insulin Therapy Added to Metformin
Baseline
Prandial Insulin (n=239)
Basal Insulin (n=234)
0.5
Biphasic Insulin (n=235)
Patients (%) with A1C >7.0
0.4
Above Normal
Density
Prandial Insulin 32.6%
Basal Insulin 36.8%
0.3
Biphasic Insulin 50.6%
0.2
0.1
0.0
0
4
8
6
10
12
A1C, %
Adapted from Holman RR, et al. N Engl J Med. 2009;361:1736-1747.
7
Hypoglycemia by Treatment: 4-T Trial
Hypoglycemia (Grade 2 or 3), %
After 3 Years of Intensified Insulin Therapy Added to Metformin
60
50
44
37
40
34
30
20
10
0
Biphasic
Insulin
Prandial
Insulin
Basal
Insulin
P=.03, prandial vs basal; P=.09, biphasic vs prandial; P=.56, biphasic vs basal; P=.09, overall
comparison between 3 groups.
Holman RR, et al. N Engl J Med. 2009;361:1736-1747.
8
Weight Gain by Treatment: 4-T Trial
After 3 Years of Intensified Insulin Therapy Added to Metformin
Mean Relative Change
in Weight, kg
12
10
8
6
5.7
6.4
3.6
4
2
0
Biphasic
Insulin
Prandial
Insulin
Basal
Insulin
P=.21, biphasic vs prandial; P=.005, biphasic vs basal; P<.001, prandial vs basal.
Holman RR, et al. N Engl J Med. 2009;361:1736-1747.
9
Daily Insulin Dose Required by
Treatment: 4-T Trial
Median Daily Insulin Dose, IU/kg
After 3 Years of Intensified Insulin Therapy Added to Metformin
1.2
1.03
.94
1.0
.78
a
a
Biphasic
Insulin
Prandial
Insulin
Basal
Insulin
0.8
0.6
0.4
The median daily
insulin dose per kg
of body weight
increased steadily
during the second
and third years of
the study
0.2
0
P=.05, biphasic vs prandial; P<.001, biphasic vs basal; P=.07, prandial vs basal.
Holman RR, et al. N Engl J Med. 2009;361:1736-1747.
10
Postprandial Glucose Contribution
to Diurnal Hyperglycemia
100
30
40
Contribution, %
80
45
50
60
70
70
40
50
20
55
60
30
0
<7.3
7.3-8.4
8.5-9.2
9.3-10.2
>10.2
A1C Range, %
Fasting Plasma Glucose
Postprandial Plasma Glucose
Monnier L, et al. Diabetes Care. 2003;26:881-885.
11
120
Defects in diabetes
60
 Deficient insulin release
0
140
 Glucagon not suppressed
(postprandially)
120
360
Glucose,
mg/dL
 Hyperglycemia
100
Meal
Glucagon,
pg/mL
Insulin,
µU/mL
Insulin Deficiency and Glucagon
Hypersecretion in Type 2 Diabetes
300
240
110
80
-60
0
60
120
180
240
T2DM Patients (n=12)
Control Patients (n=11)
Time, min
Adapted with permission from Müller WA, et al. N Engl J Med. 1970;283:109-115.
12
Type 2 Diabetes: Postprandial Glucagon
Not Corrected by Exogenous Insulin
Carbohydrate Meal
Insulin
U/mL
300
100
60
Insulin
pg/mL
20
120
100
Glucagon
Values After
Insulin Infusion
80
Values Before
Insulin Infusion
60
-60
0
60
120
180
240
Time, min
Adapted with permission from Unger RH, et al. N Engl J Med. 1971;285:443-449.
13
Amylin1,2





A neuroendocrine hormone deficient in diabetes
37-amino acid peptide first reported in 1987
Co-localized and co-secreted with insulin from pancreatic b-cells
Deficient in diabetes
Not an incretin-mimetic
Amylin
Insulin
Human amylin
1. Unger RH, Foster DW. In: Wilson J, Foster D, eds. Williams Textbook of Endocrinology.
8th ed. Philadelphia: WB Saunders Co.; 1992:1273-1275.
2. O'Brien TD, et al. Vet Pathol. 1993;30:317-332.
14
Amylin Is Co-Secreted With Insulin
and Deficient in Diabetes
25
Meal
Meal
Amylin
Insulin
Healthy male adults (n=6)
20
600
400
15
200
10
5
7 AM 12 Noon
5 PM
Time, 24-h
Midnight
0
Plasma Amylin, pmol/L
30
Meal
Plasma Insulin, pmol/L
Plasma Amylin, pmol/L
Meal
20
Without diabetes (n=27)
15
10
Insulin-using T2DM (n=27)
5
T1DM (n=190)
0
-30
0
30
60 90 120 150 180
Time After Sustacal® Meal, min
Adapted with permission from Kruger DF, et al. Diabetes Educ. 1999;25:389-397.
15
Amylin Helps Regulate Postprandial
Gycemia By Multiple Mechanisms
• Enhances feeling of fullness at meals
• Slows inappropriately accelerated
gastric emptying
• Decreases hepatic glucose output
via suppression of postprandial
pancreatic glucagon secretion
Young A. Adv Pharmacol. 2005;52:67-77.
16
Effect of Pramlintide on Postprandial Glucagon
Type 2 Diabetes, Late Stage1
30
N=12
Insulin
Meal
 Plasma Glucagon, pg/mL
Plasma Glucagon, pg/mL
60
Type 1 Diabetes2
50
40
Infusion of 100 µg/h pramlintide or placebo
30
Insulin
Meal
N=9
20
10
0
-10
Infusion of 25 µg/h pramlintide or placebo
-20
0
1
2
3
4
0
Time, h
T2DM: AUC1–4 h: P=.005.
T1DM: AUC1–5 h: P<.001.
1
2
3
4
5
Time, h
Placebo
Pramlintide
1. Adapted with permission from Fineman M, et al. Horm Metab Res. 2002;34:504-508.
2. Adapted with permission from Fineman M, et al. Metabolism. 2002;51:636-641.
17
Type 2 Diabetes1
Type 1 Diabetes2
Placebo + Insulin Lispro
Pramlintide 120 µg +
Insulin Lispro
Placebo + Insulin Lispro
Pramlintide 60 µg +
Insulin Lispro
260
Plasma Glucose, mg/dL
Mean (SE)
Plasma Glucose, mg/dL
Mean (SE)
Effect of Pramlintide on Postprandial Glucose
N=19
220
180
140
100
0
1
2
3
Time Relative to Meal and
Pramlintide, h
4
260
N=21
220
180
140
100
0
1
2
3
Time Relative to Meal and
Pramlintide, h
4
SE, standard error.
1. Adapted with permission from Maggs DG, et al. Diabetes Metab Res Rev. 2004;20:55-60.
2. Adapted with permission from Weyer C, et al. Diabetes Care. 2003;26:3074-3079.
18
Effect of Pramlintide on
Gastric Emptying
Gastric Contents
Emptied Per Hour, %
30
 Type 1 diabetes patients
(N=11) with usual insulin doses
25
a
20
a
 Administered placebo or
indicated pramlintide doses
15 minutes before ingestion of
99mTc- labeled pancake
15
10
5
 Gastric emptying monitored
by imaging
0
Placebo
aP<.004
 Crossover study
30 µg
60 µg
Pramlintide Pramlintide
versus placebo.
Kong MF, et al. Diabetologia. 1998;41:577-583.
19
Effect of Pramlintide on Caloric Intake
Obese Patients Without
Diabetes (N=15)
Patients With
Type 2 Diabetes (N=11)
-170 kcal
(-16%) P<.02
1000
Carb
750
500
-202 kcal
(-23%)
P<.01
1250
Carb
Fat
Fat
250
Protein
Protein
0
Mean Total Caloric Intake, kcal
Mean Total Caloric Intake, kcal
1250
1000
750
Carb
Carb
500
Fat
Fat
250
Protein
Protein
0
Placebo
120 µg
Pramlintide
Placebo
Adapted with permission from Chapman I, et al. Diabetologia. 2005;48:838-848.
120 µg
Pramlintide
20
Effects of Pramlintide at 26 Weeks in
Patients With Type 1 Diabetes1-3
Pooled Analysis of 3 Phase 3 Clinical Trials
 A1C, %
 Weight, kg
 Insulin Doses, %
Rapid/Short-Acting
Long-Acting
1.0
-0.0
-0.2
-0.8
+2.5%
+1.9%
+0.6 kg
0.5
3.0
0
-0.1%
2.0
-0.4
-0.6
+1.7%
-0.5
1.0
-1.0
0.0
a
-0.43%
-1.5
a
-1.0
-1.1 kg
-2.0
Placebo + Insulin (n=538)
30 or 60 µg Pramlintide + Insulin (n=716)
-3.0
-4.0
aP<.05.
1. Symlin [package insert]. Amylin Pharmaceuticals, Inc; San Diego, CA; 2008.
2. Whitehouse FW, et al. Diabetes Care. 2002;25:724-730.
3. Ratner R, et al. Diabet Med. 2004;21:1204-1212.
-3.6%
21
Effects of Pramlintide at 26 Weeks in
Patients with Type 2 Diabetes1,2
Pooled Analysis of 2 Phase 3 Clinical Trials
 Weight, kg
 A1C, %
 Insulin Doses, %
Rapid/Short-Acting
1.0
-0.0
0.5
-0.2
-0.4
+0.2 kg
-0.17%
Long-Acting
8.0
0
+5.2%
6.0
-0.5
4.0
-1.0
-0.6
-0.8
+6.5%
a
-1.5
-0.57%
–2.0
2.0
a
-1.5 kg
Placebo + Insulin (n=284)
120 µg Pramlintide + Insulin (n=292)
0.0
-2.0
a
-0.2%
-4.0
a
-3.0%
aP<.05.
1. Symlin [package insert]. Amylin Pharmaceuticals, Inc; San Diego, CA; 2008.
2. Hollander PA, et al. Diabetes Care. 2003;26:784-790.
22
Effect of Pramlintide on Diurnal Glucose
Excursions in Patients With Type 2 Diabetes
Mean (SE) Plasma Glucose, mg/dL
Clinical Practice Trial
220
Baseline
(insulin alone)
200
180
160
140
a
a
a
a
a
a
a
6 Months
(insulin + pramlintide)
120
N=166 at baseline; aP<.05; SE, standard error.
Reproduced with permission from Karl D, et al. Diabetes Technol Ther. 2007;9:191-199.
23
Effects of Pramlintide at 6 Months
in Patients With Type 2 Diabetes
Clinical Practice Trial
 A1C, %
 Weight, kg
 Insulin Use, %
-0.0
0
0
-0.2
-1
-4
-0.4
-8
-2
-4.2%
a
-12
-0.6
-0.8
Mealtime Basal Total
-6.4%
-3
a
a
-0.56%
-4
-2.8 kg
-16
a
-10.3%
120 µg Pramlintide + Insulin (N=166)
aP<.05
compared with baseline levels.
Karl D, et al. Diabetes Technol Ther. 2007;9:191-199.
24
Pramlintide vs Rapid-Acting Insulin:
Primary End Point
Patients Achieving
Composite End Point, %
In Combination With Basal Insulin in Patients With Type 2 Diabetes
35
P<.018
30
25
30
20
Composite end point = A1C ≤7.0%,
no weight gain, and no severe hypoglycemia
15
10
11
5
0
Pramlintide
n=56
Riddle M, et al. Diabetes Care. 2009;32:1577-1582.
Rapid-Acting Insulin
n=56
25
Pramlintide vs Rapid-Acting Insulin: A1C
In Combination With Basal Insulin in Patients With Type 2 Diabetes
Mean (SE) A1C, %
9.0
Pramlintide
Rapid-Acting Insulin
8.5
8.0
LS mean ∆ from baseline (LOCF)
7.5
-1.1 ± 0.2%
7.0
-1.3 ± 0.2%
6.5
6.0
0
4
8
12
16
20
24
Week
LOCF, last observation carried forward; LS, least squares; SE, standard error.
Reproduced with permission from Riddle M, et al. Diabetes Care. 2009;32:1577-1582.
26
Pramlintide vs Rapid-Acting Insulin: FPG
In Combination With Basal Insulin in Patients With Type 2 Diabetes
Mean (SE) FPG, mg/dL
175
165
Pramlintide
Rapid-Acting Insulin
155
145
LS mean ∆ from baseline (LOCF)
135
-31 ± 6 mg/dL
125
-34 ± 6 mg/dL
115
105
0
4
8
12
16
20
24
Week
LOCF, last observation carried forward; LS, least squares; SE, standard error.
Reproduced with permission from Riddle M, et al. Diabetes Care. 2009;32:1577-1582.
27
Pramlintide vs Rapid-Acting Insulin: Body Weight
Mean (SE) ∆ Body Weight, kg
In Combination With Basal Insulin in Patients With Type 2 Diabetes
Pramlintide
Rapid-Acting Insulin
5
4
LS mean ∆ from baseline (LOCF)
3
+4.7 ± 0.7 kg
2
1
0
a
a
-0.0 ± 0.7 kg
b
b
-1
b
0
4
8
12
16
20
24
Week
aP<.01
vs rapid-acting insulin; bP<.001 vs rapid-acting insulin.
LOCF, last observation carried forward; LS, least squares; SE, standard error.
Reproduced with permission from Riddle M, et al. Diabetes Care. 2009;32:1577-1582.
28
Pramlintide + Premixed Insulin in
Patients With Type 2 Diabetes
 PPG, mg/dL
 Weight, kg
 Daily Insulin
Doses, %
-0.0
-0
0
0
-0.2
-10
-1
-4
-0.4
-20
-2
-8
-0.6
-30
 A1C, %
-0.8
-0.66
-40
-12
-3
-9.1
-21.4
-16
-4
N=28; Mean (standard error [SE])
change from baseline.
-5
-4.1
Pramlintide 120 µg + Premixed Insulin (70/30 or 75/25)
Lorenzi G, et al. Presented at: 68th Scientific Sessions of the American Diabetes
Association; June 6-10, 2008; San Francisco, CA. Abstract 2119-PO.
29
Pramlintide Safety and Tolerability
 Insulin-induced severe hypoglycemia
– More common in type 1 diabetes than in type 2 diabetes
– Risk reduced by appropriate patient selection, careful patient
instruction, and insulin dose adjustments
 Nausea
– Mostly mild to moderate; occurred more frequently during
initiation and then decreased with time in most patients
– More common in type 1 diabetes than in type 2 diabetes
– Reduced by dose titration of pramlintide
Symlin [package insert]. Amylin Pharmaceuticals, Inc; San Diego, CA; 2008.
30
Pramlintide Indications
Pramlintide is given at mealtimes and is indicated for:
 Type 2 diabetes, as an adjunct treatment in patients who
use mealtime insulin therapy and have failed to achieve
desired glucose control despite optimal insulin therapy,
with or without a concurrent sulfonylurea agent and/or
metformin
 Type 1 diabetes, as an adjunct treatment in patients who
use mealtime insulin therapy and who have failed to
achieve desired glucose control despite optimal insulin
therapy
Symlin [package insert]. Amylin Pharmaceuticals, Inc; San Diego, CA; 2008.
31
Pramlintide Patient Selection:
Appropriate
Pramlintide therapy should be considered only in patients
with insulin-using type 2 or type 1 diabetes who fulfill the
following criteria:
 Have failed to achieve adequate glycemic control
despite individualized insulin management
 Are receiving ongoing care under the guidance of a
healthcare professional skilled in the use of insulin and
supported by services of diabetes educators
Symlin [package insert]. Amylin Pharmaceuticals, Inc; San Diego, CA; 2008.
32
Pramlintide Patient Selection:
Inappropriate
Exclude patients who meet any of the following criteria:
 Poor compliance with current insulin regimen
 Poor compliance with prescribed self-monitoring of blood
glucose
 A1C >9.0%
 Recurrent severe hypoglycemia requiring assistance during
past 6 months
 Hypoglycemia unawareness
 Confirmed diagnosis of gastroparesis
 Require the use of drugs that stimulate gastrointestinal motility
 Pediatric patients
Symlin [package insert]. Amylin Pharmaceuticals, Inc; San Diego, CA; 2008.
33
Initiating Pramlintide in Type 2 Diabetes
120 µg
 Start at 60 µg
– Immediately before major meal/snack
– Reduce mealtime insulin by 50%
– Frequent self-monitoring of blood glucose
60 µg
Initiation
– If no significant nausea for 3-7 days, increase pramlintide dose
 Increase pramlintide dose to 120 µg (maintenance dose)
– If nausea occurs and persists, reduce to 60 µg
– Once target dose achieved and nausea subsides, adjust
insulin doses to optimize glycemic control
Symlin [package insert]. Amylin Pharmaceuticals, Inc; San Diego, CA; 2008.
34
Initiating Pramlintide in Type 1 Diabetes
 Start 15 µg
– Immediately before major meal/snack
15 µg
– Reduce mealtime insulin by 50%
– Frequent self-monitoring of
Initiation
blood glucose
– If no significant nausea for at least 3 days,
increase pramlintide dose
60 µg
45 µg
30 µg
 Increase dose in 15-µg increments every 3 days as tolerated to
maximum of 60 µg (maintenance dose)
– If nausea occurs and persists, reduce to previous dose
– Once target dose achieved and nausea subsides, adjust
insulin doses to optimize glycemic control
Symlin [package insert]. Amylin Pharmaceuticals, Inc; San Diego, CA; 2008.
35
Administration Considerations
 Subcutaneous injection into abdomen or thigh
– Arm not recommended because of variable absorption
 Do not mix with insulin
– Can alter peak and action times of both
 Pramlintide and insulin should always be given as separate
injections and at separate sites at least 2 inches apart
– 2 inches prevents inadvertent mixing at site
 Inject before each major meal or snack containing
≥250 kcal or ≥30 g of carbohydrate
– Less carbohydrate may increase risk of hypoglycemia
Symlin [package insert]. Amylin Pharmaceuticals, Inc; San Diego, CA; 2008.
36
Discussion Question
What do you perceive are the primary reasons
for patients discontinuing pramlintide?
37
Patients’ Primary Reasons for
Discontinuing Pramlintide
28
Did not lose weight
Education re: expectations
20
Additional injections required
15
Side effects (self-reported)
Education re: expectations
13
Too expensive
9
Dosing regimen too complicated
Education re: expectations
5
Lack of effectiveness (self-reported)
0
Education re: expectations
N=127
20
40
60
80
100
Patients, %
4 of 6 primary reasons for discontinuation can be addressed
with additional education about realistic expectations, potentially
assisting 57% of patients to continue treatment
Reproduced with permission from Lorenzi GM, et al. Clin Diabetes. 2011;29:17-24.
38
Patient Barriers
 Diabetes knowledge
 Knowledge of insulin therapy
 Frequency of blood glucose monitoring
 More frequent injections
 Expectations of medication
 Cost
 Fear of hypoglycemia
 Access to diabetes education
39
Discussion Question
In your opinion, what are clinician barriers
to the use of pramlintide?
40
Healthcare Team Barriers
 Access to diabetes education
 Understanding of mechanisms of insulin
 Time required to teach patients how to use pramlintide
 Perceived benefit, or lack of benefit
 Out-of-pocket cost to patient
 Requirement for prior authorization
 Increased injection frequency
 Belief that patients will not take
 Value of weight loss
41
Discussion Question
How can patient barriers and healthcare
team barriers be overcome?
42
Overcoming Barriers
 Samples
 Starter kits
 Patient support program
 Insurance support
 Start once daily with largest meal
 Add to biphasic insulin
 Basal-bolus use
 Use of continuous glucose monitoring
43
Patient Instructions:
Hypoglycemia Precautions
 No pramlintide if no meal/snack
 No pramlintide before a snack used to treat hypoglycemia
 If quantity of food intake uncertain, consider:
– Altered timing of insulin
– Proactive insulin dose adjustment
 Patient education
– Preventive actions
– Symptom recognition and verification
– Treatment
44
Patient Instructions:
When to Call for Help
 Erratic or wide swings in blood glucose
 More frequent hypoglycemia, even if mild
 Any severe hypoglycemia
 Moderate or severe nausea
 Persistent nausea
 Vomiting
 Injection difficulties
 Any condition that may alter food intake
45
Case:
67-Year-Old African-American Man With
Type 2 Diabetes for 12 Years
Current treatment regimen/history
 The patient is currently taking insulin glargine 80 units at
10:00 PM and rapid-acting insulin 20 units tid before meals
 Lunchtime injection is skipped on most days
 A1C: 8.8%
 Weight: 90 kg; height: 5’10”; BMI: 28.3 kg/m2
 The patient has agreed to try pramlintide at dinner
46
Discussion Questions
When initiating pramlintide . . .
 When should the patient monitor his blood glucose?
 What are the patient’s blood glucose goals?
 How often would you increase the pramlintide dose?
 What would influence the pramlintide dose-titration schedule?
 How frequently would you follow up with the patient?
47
Insulin Adjustment Considerations:
Avoiding Hypoglycemia
 Pramlintide should be taken with meals or snacks that
contain at least 250 calories or 30 g of carbohydrate
 Titrating pramlintide with an appropriate decrease in insulin
will help prevent hypoglycemia
 If hypoglycemia occurs, remember that the insulin dose,
and not pramlintide, is the cause
– Re-evaluate the dose of insulin and decrease it
as needed
 The manufacturer’s directions focus on lowering the bolus
insulin dose only; while most of the blood glucose–lowering
effect involves postprandial blood glucose, it is important to
also evaluate the basal insulin dose
48
Additional Insulin Adjustment
Considerations
 If the basal insulin is greater than 50% of the total daily insulin, it may
be necessary to lower the basal insulin rate as well while patients are
increasing the pramlintide dose
 Patients who lose weight may also need a lower basal insulin rate
 Patients who take insulin are well aware of how their body responds to
their insulin dosing; when pramlintide is added, they must rethink how
their body will respond to their insulin
 Pramlintide works to reduce appetite; if patients are not sure how much
they will consume, they may wish to hold their premeal bolus or, if they
use an insulin pump, square-wave the bolus over several hours
 If the bolus is held, a blood glucose level should be taken 2-4 hours
after the meal; if the blood glucose is elevated, a correction bolus
(not a premeal bolus) can be administered
49
Case:
67-Year-Old African-American Man With
Type 2 Diabetes for 12 Years
Initiating pramlintide
 Dinnertime premeal insulin is decreased by 30%
 Pramlintide is started at 60 µg 10-15 minutes before dinner
 2-h postprandial blood glucose ranges from 120-140 mg/dL
 The patient reports mild nausea
50
Considerations for Initiating Pramlintide:
Minimizing Nausea
 There is no specific number of days that patients must stay
on a particular dose of pramlintide; the manufacturer has provided
guidelines, but the dose should be individualized based on the
patient’s response
 In addition to mild premeal nausea that may occur as pramlintide
is being titrated, patients may experience nausea if they eat
beyond the drug-induced satiety
 Gradually titrating the pramlintide dose will minimize nausea;
if nausea occurs, do not increase the pramlintide dose until the
nausea subsides
 Patients must be instructed to pay attention to the feeling
of fullness
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Case:
67-Year-Old African-American Man With
Type 2 Diabetes for 12 Years
At 1 week, he has experienced no nausea for 3 days
• Pramlintide is increased to 120 µg 10-15 minutes before dinner
and insulin is decreased an additional 20%
• No nausea with either dose
• No issues with hypoglycemia
At 4 weeks
• The patient lost 3.2 kg
• 2-hour postprandial (dinner) blood glucose ranges from
100-110 mg/dL
• Fasting blood glucose is 60-80 mg/dL
• Predinner insulin is lowered an additional 20%
• Insulin glargine is decreased to 60 units
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Discussion Question
The patient asked to use pramlintide at breakfast.
How would you proceed with his regimen?
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Case:
67-Year-Old African-American Man With
Type 2 Diabetes for 12 Years
 Breakfast premeal insulin is lowered 50%
 Pramlintide is started 60 µg; after 1 week, it is increased
to 120 µg
 After breakfast, blood glucose is 100-110 mg/dL;
insulin is lowered an additional 20%
 Over the next 8 weeks, insulin glargine is lowered to
56 units
 Prebreakfast and predinner insulin is stopped
 Pramlintide is given 120 µg at breakfast and dinner;
it is used at lunch on weekends
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Case:
67-Year-Old African-American Man With
Type 2 Diabetes for 12 Years
At 3 months




A1C: 7.6%
Weight loss: -5.5 kg
Insulin glargine: 56 units at bedtime
Premeal insulin is stopped
At 6 months





A1C: 6.0%
Weight loss: -9.1 kg
Insulin glargine: 56 units at bedtime
No premeal insulin
Pramlintide 120 µg before meals tid
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Case:
67-Year-Old African-American Man With
Type 2 Diabetes for 12 Years
Patient Outcome
 Bolus insulin ↓ by 100%
 Basal insulin ↓ by 20%
A1C, %
8.8
Weight, kg
90
BMI, kg/m2
28.3
3 months
7.6
84.5
26.5
6 months
6.0
80.9
23.7
Pre-pramlintide
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Additional Considerations for
Pramlintide Use
 Pramlintide dosing does not need to be adjusted for
physical activity
 Unopened pens of pramlintide should be kept in the
refrigerator; opened and unused pens can be kept at
room temperature for up to 28 days
 Patients who start pramlintide therapy need the support of
a diabetes educator
 The time commitment needed to start a patient on
pramlintide is similar to that of starting an insulin pump
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Conclusions- Take home messages
 Pramlintide reduces postprandial hyperglucagonemia and
hyperglycemia in patients with type 1 or type 2 diabetes
 Pramlintide also slows gastric emptying, reduces caloric intake,
and reduces diurnal glucose excursions
 In clinical trials of patients with poorly controlled diabetes on
insulin therapy, the addition of pramlintide was associated with
significant reductions in
– A1C (type 1 and type 2 diabetes)
– Body weight (type 1 and type 2 diabetes)
– Insulin use (type 2 diabetes; nonsignificant reductions in
type 1 diabetes)
 Careful patient selection, patient instruction, and insulin dose
adjustment are necessary for patients being considered for
pramlintide therapy
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Question-and-Answer
Session
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Thank you for participating!
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