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 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 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) Biphasic Insulin (n=235) 0.5

0.4

0.3

Patients (%) with A1C >7.0

Prandial Insulin 32.6% Basal Insulin 36.8% Biphasic Insulin 50.6% 0.2

Above Normal 0.1

0.0

0 4 6 A1C, % 8

Adapted from Holman RR, et al.

N Engl J Med

. 2009;361:1736-1747.

10 12

7

Hypoglycemia by Treatment: 4-T Trial

After 3 Years of Intensified Insulin Therapy Added to Metformin 60 50 40 30 20 10 0 37 44 34 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 12 10 8 6 4 2 0 5.7

6.4

Biphasic Insulin Prandial Insulin 3.6

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

After 3 Years of Intensified Insulin Therapy Added to Metformin 1.2

1.0

0.8

0.6

0.4

0.2

0 .78

Biphasic Insulin .94

a Prandial Insulin 1.03

a Basal Insulin

The median daily insulin dose per kg of body weight increased steadily during the second and third years of the study

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 80 60 40 70 20 0 30 <7.3

50 50 45 55 40 60 30 70 7.3-8.4

8.5-9.2

9.3-10.2

A1C Range, % >10.2

Fasting Plasma Glucose Postprandial Plasma Glucose

Monnier L, et al.

Diabetes Care.

2003;26:881-885.

11

Insulin Deficiency and Glucagon Hypersecretion in Type 2 Diabetes

360 300 240 110 80 120 60 0 140 120 100 -60 0 60 120 Time, min 180 240 Defects in diabetes

 Deficient insulin release  Glucagon not suppressed (postprandially)  Hyperglycemia

T2DM Patients (n=12) Control Patients (n=11)

Adapted with permission from M üller 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 300 100 60 20 120 100 80 60 Insulin Glucagon Values After Insulin Infusion Values Before Insulin Infusion -60 0 60 120 Time, min 180 240

Adapted with permission from Unger RH, et al.

N Engl J Med.

1971;285:443-449.

13

Amylin

1,2      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

30 25 20 15 Meal Meal Meal Amylin Insulin Healthy male adults (n=6) 10 5 7 AM 12 Noon 5 PM Time, 24-h Midnight 600 400 200 0 Meal 20 15 Without diabetes (n=27) 10 5 Insulin-using T2DM (n=27) 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 16 Young A.

Adv Pharmacol.

2005;52:67-77.

Effect of Pramlintide on Postprandial Glucagon

60 50 Type 2 Diabetes, Late Stage 1 Insulin Meal N=12 30 Type 1 Diabetes 2 Insulin Meal 20 10 N=9 0 40 -10 Infusion of 100 µg/h pramlintide or placebo 30 0 1 2 Time, h

T2DM: AUC 1 –4 h :

P

=.005.

T1DM: AUC 1 –5 h :

P

<.001.

3 4 -20 0 Placebo Pramlintide Infusion of 25 µg/h pramlintide or placebo 1 2 Time, h 3 4 5

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

Effect of Pramlintide on Postprandial Glucose

260 Type 2 Diabetes 1 Placebo + Insulin Lispro Pramlintide 120 µg + Insulin Lispro N=19 260 Type 1 Diabetes 2 Placebo + Insulin Lispro Pramlintide 60 µg + Insulin Lispro N=21 220 220 180 140 180 140 100 0 1 2 3 Time Relative to Meal and Pramlintide, h 4 100 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

30 25 20 15 10 5 0 a a Placebo 30 µg Pramlintide 60 µg Pramlintide

   Type 1 diabetes patients (N=11) with usual insulin doses Crossover study Administered placebo or indicated pramlintide doses 15 minutes before ingestion of 99m Tc- labeled pancake  Gastric emptying monitored by imaging a

P

<.004 versus placebo.

Kong MF, et al.

Diabetologia.

1998;41:577-583.

19

Effect of Pramlintide on Caloric Intake

1250 Obese Patients Without Diabetes (N=15) -170 kcal (-16%) P<.02

1000 750 500 250 0 Carb Carb Fat Fat Protein Protein Placebo 120 µg Pramlintide 1250 1000 750 500 250 0 Patients With Type 2 Diabetes (N=11) -202 kcal (-23%) P<.01

Carb Carb Fat Fat Protein Placebo Protein 120 µg Pramlintide

Adapted with permission from Chapman I, et al.

Diabetologia.

2005;48:838-848.

20

-0.0

-0.2

-0.4

-0.6

-0.8

Effects of Pramlintide at 26 Weeks in Patients With Type 1 Diabetes

1-3

Pooled Analysis of 3 Phase 3 Clinical Trials



A1C, %



Weight, kg -0.1% a -0.43% 1.0

0.5

0 -0.5

-1.0

-1.5

+0.6 kg a -1.1 kg Placebo + Insulin (n=538) 30 or 60 µg Pramlintide + Insulin (n=716)



Insulin Doses, % Rapid/Short-Acting Long-Acting +1.7% +2.5% +1.9% 3.0

2.0

1.0

0.0

-1.0

-2.0

-3.0

-4.0

a

P

<.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

-0.0

-0.2

-0.4

-0.6

-0.8

Effects of Pramlintide at 26 Weeks in Patients with Type 2 Diabetes

1,2

Pooled Analysis of 2 Phase 3 Clinical Trials



A1C, %



Weight, kg



Insulin Doses, % Rapid/Short-Acting -0.17% a -0.57% 1.0

0.5

0 -0.5

-1.0

-1.5

–2.0

+0.2 kg a -1.5 kg Placebo + Insulin (n=284) 120 µg Pramlintide + Insulin (n=292) 8.0

6.0

4.0

2.0

0.0

-2.0

-4.0

+6.5% a -3.0% Long-Acting +5.2% a -0.2%

a

P

<.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

Clinical Practice Trial 220 200 180 160 140 120 a a a a a a Baseline (insulin alone) a 6 Months (insulin + pramlintide)

N=166 at baseline; a

P

<.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 -0.0

-0.2

-0.4

-0.6

-0.8



A1C, % a -0.56%



0 -1 -2 -3 -4 Weight, kg a -2.8 kg



Insulin Use, % 0 Mealtime Basal Total -4 -8 -12 -16 a -10.3% -4.2% a -6.4% 120 µg Pramlintide + Insulin (N=166)

a

P

<.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

In Combination With Basal Insulin in Patients With Type 2 Diabetes 35 30 25 20 15 10 5 0 P<.018

30

Composite end point = A1C ≤7.0%, no weight gain, and no severe hypoglycemia

Pramlintide n=56 11 Rapid-Acting Insulin n=56

Riddle M, et al.

Diabetes Care.

2009;32:1577-1582.

25

Pramlintide vs Rapid-Acting Insulin: A1C

In Combination With Basal Insulin in Patients With Type 2 Diabetes 9.0

8.5

8.0

7.5

7.0

6.5

6.0

Pramlintide Rapid-Acting Insulin

LS mean ∆ from baseline (LOCF)

-1.1 ± 0.2% -1.3 ± 0.2% 0 4 8 Week 12 16 20 24

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 175 165 155 145 135 125 115 105 Pramlintide Rapid-Acting Insulin

LS mean ∆ from baseline (LOCF)

-31 ± 6 mg/dL -34 ± 6 mg/dL 0 4 8 12 Week 16 20 24

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

In Combination With Basal Insulin in Patients With Type 2 Diabetes 1 0 -1 3 2 5 4 0 Pramlintide Rapid-Acting Insulin

a

4

LS mean ∆ from baseline (LOCF)

+4.7 ± 0.7 kg

a

8

b

12 Week 16

b

20

b

-0.0 ± 0.7 kg 24

a

P

<.01 vs rapid-acting insulin; b

P

<.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

-0.0



A1C, % -0.2

Pramlintide + Premixed Insulin in Patients With Type 2 Diabetes



PPG, mg/dL -0 -10



Weight, kg 0 -1



Daily Insulin Doses, % 0 -4 -20 -0.4

-2 -8 -12 -0.6

-30 -3 -9.1

-0.66

-21.4

-0.8

-40 -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



60 µg 120 µg

Start at 60 µg – Immediately before major meal/snack – – – Reduce mealtime insulin by 50% Frequent self-monitoring of blood glucose

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 Reduce mealtime insulin by 50% Frequent self-monitoring of blood glucose – If no significant nausea for at least 3 days, increase pramlintide dose

15 µg Initiation 30 µg 45 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

60 µg

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

Did not lose weight Additional injections required Side effects (self-reported) Too expensive Dosing regimen too complicated Lack of effectiveness (self-reported) 0 5 15 20 9 13 28 Education re: expectations Education re: expectations Education re: expectations Education re: expectations

N=127

20 40 60 Patients, % 80 100

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/m 2  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 51

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 52

Discussion Question

The patient asked to use pramlintide at breakfast. How would you proceed with his regimen?

53

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 54

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 55

Case:

67-Year-Old African-American Man With Type 2 Diabetes for 12 Years Patient Outcome

  Bolus insulin ↓ by 100% Basal insulin ↓ by 20% Pre-pramlintide 3 months 6 months

A1C, %

8.8

7.6

6.0

Weight, kg

90 84.5

80.9

BMI, kg/m 2

28.3

26.5

23.7

56

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 57

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 58

Question-and-Answer Session

59

Thank you for participating!

60