1. 2 accreditation and designation of credit the network for continuing medical education ( ncme) is...

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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.

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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

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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



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


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




28

aP<.01 vs rapid-acting insulin; bP<.001 vs rapid-acting insulin.


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


a


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


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


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


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


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


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


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




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


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


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


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


56

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


57

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

58

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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Documents

insulin slide

biphasic insulin n

baseline prandial insulin

insulin target glucose

suggested insulin doses

biphasic vs prandial

prandial vs basal p

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