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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.
3
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.
Faculty DisclosureCurtis Triplitt, PharmD
Texas Diabetes InstituteClinical 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
5
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 amylin- replacement 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
6
Limitations of Intensified Insulin Therapy Added to Oral Therapy: 4-T Trial
Type 2 Diabetes: Metformin + Sulfonylurea Failure
Basal Insulin (n=234)Prandial Insulin (n=239) Biphasic Insulin (n=235)
If A1C levels unacceptable on or after week 24, add second insulin
• 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
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)
Holman RR, et al. N Engl J Med. 2009;361:1736-1747.
7
Distribution of A1C Levels: 4-T TrialAfter 3 Years of Intensified Insulin Therapy Added to Metformin
Adapted from Holman RR, et al. N Engl J Med. 2009;361:1736-1747.
0.0
0.1
0.2
0.3
0.4
0.5
0 4 6 8 10 12
A1C, %
Baseline
Prandial Insulin (n=239)
Basal Insulin (n=234)
Biphasic Insulin (n=235)
Above Normal
De
nsi
ty
Prandial Insulin 32.6%
Basal Insulin 36.8%
Biphasic Insulin 50.6%
Patients (%) with A1C >7.0
Hypoglycemia by Treatment: 4-T TrialAfter 3 Years of Intensified Insulin Therapy Added to Metformin
8
Hyp
og
lyce
mia
(G
rad
e 2
or
3),
%
0
10
20
30
40
50
60
BiphasicInsulin
Prandial Insulin
Basal Insulin
3744
34
Holman RR, et al. N Engl J Med. 2009;361:1736-1747.
P=.03, prandial vs basal; P=.09, biphasic vs prandial; P=.56, biphasic vs basal; P=.09, overall comparison between 3 groups.
9Holman RR, et al. N Engl J Med. 2009;361:1736-1747.
Weight Gain by Treatment: 4-T TrialAfter 3 Years of Intensified Insulin Therapy Added to Metformin
Mea
n R
elat
ive
Ch
ang
ein
W
eig
ht,
kg
P=.21, biphasic vs prandial; P=.005, biphasic vs basal; P<.001, prandial vs basal.
0
2
4
6
8
10
12
BiphasicInsulin
Prandial Insulin
Basal Insulin
5.76.4
3.6
10Holman RR, et al. N Engl J Med. 2009;361:1736-1747.
Daily Insulin Dose Required by Treatment: 4-T Trial
After 3 Years of Intensified Insulin Therapy Added to Metformin M
edia
n D
aily
In
suli
n D
ose
, IU
/kg
a a
P=.05, biphasic vs prandial; P<.001, biphasic vs basal; P=.07, prandial vs basal.
0
0.2
0.4
0.6
0.8
1.0
1.2
BiphasicInsulin
Prandial Insulin
Basal Insulin
.78
.941.03
The median daily insulin dose per kg of body weight increased steadily during the second and third years of the study
11Monnier L, et al. Diabetes Care. 2003;26:881-885.
70
Postprandial Glucose Contribution to Diurnal Hyperglycemia
Co
ntr
ibu
tio
n,
%
A1C Range, %
0
20
40
60
80
100
Postprandial Plasma Glucose
>10.29.3-10.28.5-9.27.3-8.4<7.3
50
Fasting Plasma Glucose
30
55
50
3040
70
45
60
12
Mea
l
Adapted with permission from Müller WA, et al. N Engl J Med. 1970;283:109-115.
Insulin Deficiency and Glucagon Hypersecretion in Type 2 Diabetes
Defects in diabetes
Deficient insulin release
Glucagon not suppressed (postprandially)
Hyperglycemia
120
60
0Insu
lin,
µU
/mL
100
120
140
-60 0 60 120 180 240
Time, min
Glu
cag
on
,p
g/m
L
360
300
24011080
Glu
cose
,m
g/d
L
Control Patients (n=11)
T2DM Patients (n=12)
13
Type 2 Diabetes: Postprandial Glucagon Not Corrected by Exogenous Insulin
Adapted with permission from Unger RH, et al. N Engl J Med. 1971;285:443-449.
Carbohydrate Meal
300
60U/m
Lp
g/m
L Glucagon
Insulin100
2020
120120
100100
8080
6060
Time, min
--60 0 60 120 180 240
Insulin
Values Before Insulin Infusion
Values After Insulin Infusion
14
Amylin Insulin
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 -cells Deficient in diabetes Not an incretin-mimetic
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.
Human amylin
15
Time After Sustacal® Meal, min
0
5
10
15
20
-30 0 30 60 90 120 150 180P
lasm
a A
myl
in, p
mo
l/L
Meal
T1DM (n=190)
Insulin-using T2DM (n=27)
Without diabetes (n=27)Without diabetes (n=27)
Amylin Is Co-Secreted With Insulinand Deficient in Diabetes
Pla
sma
Insu
lin, p
mo
l/L
30
25
20
15
10
5
Time, 24-h
600
400
200
0
Meal Meal Meal
AmylinInsulin
Pla
sma
Am
ylin
, pm
ol/L
Healthy male adults (n=6)
Adapted with permission from Kruger DF, et al. Diabetes Educ. 1999;25:389-397.
7 AM Midnight5 PM12 Noon
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
16
Young A. Adv Pharmacol. 2005;52:67-77.
17
Effect of Pramlintide on Postprandial Glucagon
Type 1 Diabetes2
Time, h
PlaceboPramlintide
Infusion of 25 µg/h pramlintide or placebo
-20
0
10
20
30
-10
InsulinMeal
0 2 3 4 51
Type 2 Diabetes, Late Stage1
Time, h
Pla
sma
Glu
cag
on
, p
g/m
L
InsulinMeal
60
40
30
50
Infusion of 100 µg/h pramlintide or placebo
0 1 2 3 4
Pla
sma
Glu
cag
on
, p
g/m
L
T2DM: AUC1–4 h: P=.005.T1DM: AUC1–5 h: P<.001.
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.
N=12 N=9
18
Effect of Pramlintide on Postprandial Glucose
Type 2 Diabetes1 Type 1 Diabetes2
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.
0 1 2 3 4100
140
180
220
260
Time Relative to Meal and Pramlintide, h
Pla
sma
Glu
cose
, mg
/dL
Mea
n (
SE
)
0 1 2 3 4Time Relative to Meal and
Pramlintide, h
Pla
sma
Glu
cose
, mg
/dL
Mea
n (
SE
)100
140
180
220
260
Placebo + Insulin Lispro
Pramlintide 120 µg + Insulin Lispro
Placebo + Insulin Lispro
Pramlintide 60 µg + Insulin Lispro
N=19 N=21
SE, standard error.
19
Type 1 diabetes patients (N=11) with usual insulin doses
Crossover study
Administered placebo or indicated pramlintide doses 15 minutes before ingestion of 99mTc- labeled pancake
Gastric emptying monitored by imaging
Kong MF, et al. Diabetologia. 1998;41:577-583.
Effect of Pramlintide on Gastric Emptying
Gas
tric
Co
nte
nts
E
mp
tied
Per
Ho
ur,
%
a a
aP<.004 versus placebo.
0
5
10
15
20
25
30
Placebo 30 µgPramlintide
60 µgPramlintide
20
0
250
500
750
1000
1250
Mea
n T
ota
l C
alo
ric
Inta
ke,
kcal
0
250
500
750
1000
1250
Fat
Carb
Carb
Fat
Protein Protein
Effect of Pramlintide on Caloric Intake
-170 kcal(-16%) P<.02
Carb
Carb
FatFat
Protein
-202 kcal(-23%)P<.01
Patients With Type 2 Diabetes (N=11)
Mea
n T
ota
l C
alo
ric
Inta
ke,
kcal
Obese Patients Without Diabetes (N=15)
Protein
Placebo 120 µgPramlintide
Placebo 120 µgPramlintide
Adapted with permission from Chapman I, et al. Diabetologia. 2005;48:838-848.
21
Effects of Pramlintide at 26 Weeks in Patients With Type 1 Diabetes1-3
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.
+0.6 kg
-1.1 kga-1.5
-1.0
-0.5
0
0.5
Placebo + Insulin (n=538)30 or 60 µg Pramlintide + Insulin (n=716)
1.0
-0.1%
a
-0.43%-0.8
-0.6
-0.4
-0.2
-0.0
A1C, % Insulin Doses, % Weight, kg
+1.7%+2.5%
+1.9%
-3.6%
Rapid/Short-ActingLong-Acting
aP<.05.
-4.0
-3.0
-2.0
-1.0
0.0
1.0
2.0
3.0
Pooled Analysis of 3 Phase 3 Clinical Trials
22
Effects of Pramlintide at 26 Weeks in Patients with Type 2 Diabetes1,2
Placebo + Insulin (n=284)120 µg Pramlintide + Insulin (n=292)
1. Symlin [package insert]. Amylin Pharmaceuticals, Inc; San Diego, CA; 2008.2. Hollander PA, et al. Diabetes Care. 2003;26:784-790.
–2.0
-1.5
-1.0
-0.5
0
0.5
A1C, % Insulin Doses, % Weight, kg
-0.17%
+0.2 kg
-0.8
-0.6
-0.4
-0.2
-0.0
a
-1.5 kg
1.0
a-0.57%
+6.5%
+5.2%
a
-0.2%
a
-3.0%
Rapid/Short-Acting
Long-Acting
aP<.05.
-4.0
-2.0
0.0
2.0
4.0
6.0
8.0
Pooled Analysis of 2 Phase 3 Clinical Trials
23
Effect of Pramlintide on Diurnal Glucose Excursions in Patients With Type 2 Diabetes
Reproduced with permission from Karl D, et al. Diabetes Technol Ther. 2007;9:191-199.
a
a
a
a
a
a a
Prebreakfast
Postbreakfast
Prelunch
Postlunch
Predinner
Postdinner
Bedtime
Baseline (insulin alone)
6 Months (insulin + pramlintide)
Mea
n (
SE
) P
lasm
a G
luco
se, m
g/d
L
N=166 at baseline; aP<.05; SE, standard error.
220
200
180
160
140
120
Clinical Practice Trial
24
Effects of Pramlintide at 6 Months in Patients With Type 2 Diabetes
aP<.05 compared with baseline levels.
-0.56%a-0.8
-0.6
-0.4
-0.2
-0.0
A1C, %
-10.3%
-4.2%
-6.4%
a
a
TotalBasalMealtime
-16
-12
-8
-4
0
Insulin Use, %
-2.8 kga
-4
-3
-2
-1
0
Weight, kg
120 µg Pramlintide + Insulin (N=166)
Karl D, et al. Diabetes Technol Ther. 2007;9:191-199.
Clinical Practice Trial
25
Pramlintide vs Rapid-Acting Insulin: Primary End Point
Riddle M, et al. Diabetes Care. 2009;32:1577-1582.
P<.018
Pramlintiden=56
Rapid-Acting Insulinn=56
0
5
10
15
20
25
30
35
30
11Pat
ien
ts A
chie
vin
g
Co
mp
osi
te E
nd
Po
int,
%
Composite end point = A1C ≤7.0%, no weight gain, and no severe hypoglycemia
In Combination With Basal Insulin in Patients With Type 2 Diabetes
26Reproduced with permission from Riddle M, et al. Diabetes Care. 2009;32:1577-1582.
0 4 8 12 16 20 246.0
6.5
7.0
7.5
8.0
8.5
9.0
PramlintideRapid-Acting Insulin
-1.3 ± 0.2%
-1.1 ± 0.2%
LS mean ∆ from baseline (LOCF)
Week
Mea
n (
SE
) A
1C,
%Pramlintide vs Rapid-Acting Insulin: A1C
In Combination With Basal Insulin in Patients With Type 2 Diabetes
LOCF, last observation carried forward; LS, least squares; SE, standard error.
27 Reproduced with permission from Riddle M, et al. Diabetes Care. 2009;32:1577-1582.
0 4 8 12 16 20 24105
115
125
135
145
155
165
175
PramlintideRapid-Acting Insulin
-34 ± 6 mg/dL
-31 ± 6 mg/dL
Week
Mea
n (
SE
) F
PG
, m
g/d
LPramlintide vs Rapid-Acting Insulin: FPG
In Combination With Basal Insulin in Patients With Type 2 Diabetes
LS mean ∆ from baseline (LOCF)
LOCF, last observation carried forward; LS, least squares; SE, standard error.
28
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.
0 4 8 12 16 20 24
-1
0
1
2
3
4
5 PramlintideRapid-Acting Insulin
a-0.0 ± 0.7 kg
+4.7 ± 0.7 kg
Week
Mea
n (
SE
) ∆
Bo
dy
Wei
gh
t, k
g
bb
b
Pramlintide vs Rapid-Acting Insulin: Body Weight
LS mean ∆ from baseline (LOCF)
a
In Combination With Basal Insulin in Patients With Type 2 Diabetes
29
N=28; Mean (standard error [SE]) change from baseline.
Pramlintide + Premixed Insulin in Patients With Type 2 Diabetes
-4
-3
-2
-1
-5
-0.66
-4.1
-9.1
-0.8
-0.6
-0.4
-0.2
-0.0 0
-16
-12
-8
-4
0
A1C, % Daily Insulin
Doses, % Weight, kg
Pramlintide 120 µg + Premixed Insulin (70/30 or 75/25)
-21.4-40
-30
-20
-10
-0
PPG, mg/dL
Lorenzi G, et al. Presented at: 68th Scientific Sessions of the American Diabetes Association; June 6-10, 2008; San Francisco, CA. Abstract 2119-PO.
30
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.
31
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.
32
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.
33
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.
34
Initiating Pramlintide in Type 2 Diabetes
Start at 60 µg
– Immediately before major meal/snack
– Reduce mealtime insulin by 50%
– Frequent self-monitoring of blood glucose
– 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
Initiation
120 µg
60 µg
Symlin [package insert]. Amylin Pharmaceuticals, Inc; San Diego, CA; 2008.
35
Initiating Pramlintide in Type 1 Diabetes
Start 15 µg
– Immediately before major meal/snack
– Reduce mealtime insulin by 50%
– Frequent self-monitoring of blood glucose
– If no significant nausea for at least 3 days, increase pramlintide dose
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
15 µg
30 µg
45 µg
60 µg
Initiation
Symlin [package insert]. Amylin Pharmaceuticals, Inc; San Diego, CA; 2008.
36
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.
37
Discussion Question
What do you perceive are the primary reasons for patients discontinuing pramlintide?
38
Patients’ Primary Reasons for Discontinuing Pramlintide
Did not lose weight
Side effects (self-reported)
Additional injections required
Too expensive
Dosing regimen too complicated
Lack of effectiveness (self-reported)
Education re: expectations
Education re: expectations
Education re: expectations
Education re: expectations
4 of 6 primary reasons for discontinuation can be addressed with additional education about realistic expectations, potentially
assisting 57% of patients to continue treatment
28
20
15
13
9
5
0 20 40 60 80 100
Patients, %
N=127
Reproduced with permission from Lorenzi GM, et al. Clin Diabetes. 2011;29:17-24.
39
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
40
Discussion Question
In your opinion, what are clinician barriers to the use of pramlintide?
41
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
42
Discussion Question
How can patient barriers and healthcare team barriers be overcome?
43
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
44
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
45
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
46
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
Case:67-Year-Old African-American Man With Type 2 Diabetes for 12 Years
47
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?
48
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
49
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
50
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
Case:67-Year-Old African-American Man With Type 2 Diabetes for 12 Years
51
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
52
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
Case:67-Year-Old African-American Man With Type 2 Diabetes for 12 Years
53
The patient asked to use pramlintide at breakfast. How would you proceed with his regimen?
Discussion Question
54
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
Case:67-Year-Old African-American Man With Type 2 Diabetes for 12 Years
55
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
Case:67-Year-Old African-American Man With Type 2 Diabetes for 12 Years
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Patient Outcome
Bolus insulin ↓ by 100% Basal insulin ↓ by 20%
A1C, % Weight, kg BMI, kg/m2
Pre-pramlintide 8.8 90 28.3
3 months 7.6 84.5 26.5
6 months 6.0 80.9 23.7
Case:67-Year-Old African-American Man With Type 2 Diabetes for 12 Years
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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!