Patient Site

INDICATIONS

SYMLIN® (pramlintide acetate) is indicated as adjunct treatment in adults with type 1 or type 2 diabetes who use mealtime insulin therapy and who have failed to achieve desired glucose control despite optimal insulin therapy (with or without a concurrent sulfonylurea agent and/or metformin in type 2 diabetes).

IMPORTANT SAFETY INFORMATION

WARNING: SEVERE HYPOGLYCEMIA
SYMLIN is used with insulin and has been associated with an increased risk of insulin induced severe hypoglycemia, particularly in patients with type 1 diabetes. When severe hypoglycemia associated with SYMLIN use occurs, it is seen within 3 hours following a SYMLIN injection. If severe hypoglycemia occurs while operating a motor vehicle, heavy machinery, or while engaging in other high-risk activities, serious injuries may occur. Appropriate patient selection, careful patient instruction, and insulin dose adjustments are critical elements for reducing this risk.
Click here for additional Important Safety Information.

SAFETY PROFILE

IMPORTANT SAFETY INFORMATION

WARNING: SEVERE HYPOGLYCEMIA
SYMLIN is used with insulin and has been associated with an increased risk of insulin induced severe hypoglycemia, particularly in patients with type 1 diabetes. When severe hypoglycemia associated with SYMLIN use occurs, it is seen within 3 hours following a SYMLIN injection. If severe hypoglycemia occurs while operating a motor vehicle, heavy machinery, or while engaging in other high-risk activities, serious injuries may occur. Appropriate patient selection, careful patient instruction, and insulin dose adjustments are critical elements for reducing this risk.
Click here for additional Important Safety Information.

CONTRAINDICATIONS

  • Known hypersensitivity to SYMLIN or any of its components, including metacresol
  • Confirmed diagnosis of gastroparesis
  • Hypoglycemia unawareness

WARNINGS

Proper patient selection is critical to safe and effective use of SYMLIN: Review HbA1c, recent blood glucose monitoring data, history of insulin-induced hypoglycemia, current insulin regimen, and body weight before initiation of therapy. Only consider SYMLIN for 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 insulin-use and supported by a diabetes educator

Do NOT consider SYMLIN for patients meeting any of the following criteria:

  • poor compliance with current insulin regimen
  • poor compliance with prescribed self-blood glucose monitoring
  • HbA1c >9%
  • recurrent severe hypoglycemia requiring assistance during the past 6 months
  • presence of hypoglycemia unawareness
  • confirmed diagnosis of gastroparesis
  • require the use of drugs that stimulate gastrointestinal motility
  • pediatric patients

Hypoglycemia: SYMLIN (pramlintide acetate) alone does not cause hypoglycemia. However, SYMLIN is indicated to be co-administered with insulin therapy and in this setting SYMLIN increases the risk of insulin-induced severe hypoglycemia, particularly in patients with type 1 diabetes. Severe hypoglycemia associated with SYMLIN occurs within the first 3 hours following a SYMLIN injection. Serious injuries may occur if severe hypoglycemia occurs while operating a motor vehicle, heavy machinery, or while engaging in other high-risk activities.
Therefore, when introducing SYMLIN therapy, appropriate precautions need to be taken to avoid increasing the risk for insulin-induced severe hypoglycemia. These precautions include frequent pre- and post-meal glucose monitoring combined with an initial 50% reduction in pre-meal doses of short-acting insulin. The addition of any antihyperglycemic agent such as SYMLIN to an existing regimen of one or more antihyperglycemic agents (e.g., insulin, sulfonylurea), or other agents that can increase the risk of hypoglycemia may necessitate further insulin dose adjustments; closely monitor blood glucose.

PRECAUTIONS

Never mix SYMLIN and insulin: Administer as separate injections. Mixing can alter the pharmacokinetics of both products.

Allergy: Local allergies such as redness, swelling, or itching at the site of injection may occur. The incidence of systemic allergic reactions was 5% for SYMLIN plus insulin vs. 4%-5% for placebo plus insulin.

Drug Interactions: SYMLIN slows gastric emptying. Do not administer with drugs that alter gastrointestinal motility (e.g., anticholinergic agents such as atropine) or that slow the intestinal absorption of nutrients (e.g., α–glucosidase inhibitors). SYMLIN has the potential to delay the absorption of concomitantly administered oral medications; if rapid onset is a critical determinant of effectiveness (such as analgesics), the agent should be administered at least 1 hour prior to or 2 hours after SYMLIN injection.

Pregnant and Nursing Women: No adequate and well controlled studies have been conducted in pregnant women. It is unknown whether SYMLIN is excreted in human milk. SYMLIN should only be used in pregnancy or while nursing if the potential benefit justifies the potential risk.

ADVERSE REACTIONS

Most common adverse events reported in ≥ 5% of patients treated with SYMLIN plus insulin and with greater incidence than in patients treated with placebo plus insulin were:

  • Type 2 Diabetes: nausea (28% vs. 12%), headache (13% vs. 7%), anorexia (9% vs. 2%), vomiting (8% vs. 4%), abdominal pain (8% vs. 7%), fatigue (7% vs. 4%), dizziness (6% vs. 4%), coughing (6% vs. 4%), pharyngitis (5% vs. 2%).
  • Type 1 Diabetes: nausea (48% vs. 17%), anorexia (17% vs. 2%), inflicted injury (14% vs. 10%), vomiting (11% vs. 7%), arthralgia (7% vs. 5%), fatigue (7% vs. 4%), allergic reaction (6% vs. 5%), dizziness (5% vs. 4%).

The incidence for severe hypoglycemic adverse events in placebo-controlled trials with SYMLIN plus insulin vs. placebo plus insulin and with greater incidence than in patients treated with placebo plus insulin were:

  • Type 2 Diabetes: Patient-ascertained severe hypoglycemia at 0-3 months (8.2% vs. 2.1%) and at >3-6 months (4.7% vs. 2.4%). Medically assisted severe hypoglycemia at 0-3 months (1.7% vs. 0.7%).
  • Type 1 Diabetes: Patient-ascertained severe hypoglycemia at 0-3 months (16.8% vs. 10.8%) and at >3-6 months (11.1% vs. 8.7%). Medically assisted severe hypoglycemia at 0-3 months (7.3% vs. 3.3%) and at >3-6 months (5.2% vs. 4.3%).

SYMLIN DESCRIPTION

SYMLIN (pramlintide acetate) injection is an anti-diabetic medication for use in patients with diabetes treated with insulin. SYMLIN is a synthetic analog of human amylin, a naturally occurring neuroendocrine hormone synthesized by pancreatic beta cells that contributes to glucose control during the postprandial period.

THE HORMONE AMYLIN

Insulin and amylin are partner hormones1,2

  • Both hormones are produced by pancreatic beta cells
  • Both are secreted in response to food intake
  • Both impact PPG

Mean 24-hour secretion profile of amylin and insulin in healthy adults (n = 6)1,2

In patients with diabetes, amylin secretion is deficient

  • Damaged or dysfunctional pancreatic beta cells can lead to reductions in secretion of both insulin and amylin in response to food
  • Insulin and amylin may need to be replaced
  • Insulin increases glucose uptake in cells
  • Amylin decreases glucose appearance in the bloodstream after a meal(3)

CONTRAINDICATIONS

  • Known hypersensitivity to SYMLIN or any of its components, including metacresol
  • Confirmed diagnosis of gastroparesis
  • Hypoglycemia unawareness

PHARMACODYNAMICS

SYMLIN reduced postprandial plasma glucose (PPG) concentrations when administered prior to a meal with mealtime insulin1,4,5

Regular insulin: type 1 patients

Lispro insulin: type 1 patients

Lispro insulin: type 2 patients

A randomized, single-blind, placebo-controlled, five-way crossover pharmacodynamic study evaluated postprandial glucose concentrations of pramlintide in combination with insulin lispro or regular insulin in adult patients with type 1 or type 2 diabetes who underwent a standardized mixed meal test for 5 consecutive days.

WARNINGS

Proper patient selection is critical to safe and effective use of SYMLIN: Review HbA1c, recent blood glucose monitoring data, history of insulin-induced hypoglycemia, current insulin regimen, and body weight before initiation of therapy.
Only consider SYMLIN for 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 insulin-use and supported by a diabetes educator

Do NOT consider SYMLIN for patients meeting any of the following criteria:

  • poor compliance with current insulin regimen
  • poor compliance with prescribed self-blood glucose monitoring
  • HbA1c >9%
  • recurrent severe hypoglycemia requiring assistance during the past 6 months
  • presence of hypoglycemia unawareness
  • confirmed diagnosis of gastroparesis
  • require the use of drugs that stimulate gastrointestinal motility
  • pediatric patients

PHARMACODYNAMICS

The reduction in PPG limited glucose fluctuations based on 24-hour glucose monitoring when SYMLIN was added to insulin6,7

Type 1: change in self-monitored 7-point glucose profile

Type 2: change in self-monitored 7-point glucose profile

Hypoglycemia: SYMLIN (pramlintide acetate) alone does not cause hypoglycemia. However, SYMLIN is indicated to be co-administered with insulin therapy and in this setting SYMLIN increases the risk of insulin-induced severe hypoglycemia, particularly in patients with type 1 diabetes. Severe hypoglycemia associated with SYMLIN occurs within the first 3 hours following a SYMLIN injection. Serious injuries may occur if severe hypoglycemia occurs while operating a motor vehicle, heavy machinery, or while engaging in other high-risk activities.
Therefore, when introducing SYMLIN therapy, appropriate precautions need to be taken to avoid increasing the risk for insulin-induced severe hypoglycemia. These precautions include frequent pre- and post-meal glucose monitoring combined with an initial 50% reduction in pre-meal doses of short-acting insulin. The addition of any antihyperglycemic agent such as SYMLIN to an existing regimen of one or more antihyperglycemic agents (e.g., insulin, sulfonylurea), or other agents that can increase the risk of hypoglycemia may necessitate further insulin dose adjustments; closely monitor blood glucose.

A 6-month, phase 3, open-label, single-arm multicenter trial evaluated the efficacy and safety of pramlintide in adult patients with type 1 or type 2 diabetes who had inadequate glycemic control (A1C ≥7.0% and ≤11.0%) using insulin therapy.

MECHANISM OF ACTION

SYMLIN has 3 mechanisms to help reduce the rate of PPG appearance1

SYMLIN® (pramlintide acetate) injection is a synthetic analogue of amylin

  • SYMLIN is indicated as adjunct treatment in adults with type 1 or type 2 diabetes who use mealtime insulin therapy and who have failed to achieve desired glucose control despite optimal insulin therapy (with or without a concurrent sulfonylurea agent and/or metformin in type 2 diabetes).

PRECAUTIONS

Never mix SYMLIN and insulin: Administer as separate injections. Mixing can alter the pharmacokinetics of both products.

Allergy: Local allergies such as redness, swelling, or itching at the site of injection may occur. The incidence of systemic allergic reactions was 5% for SYMLIN plus insulin vs. 4%-5% for placebo plus insulin.

Drug Interactions: SYMLIN slows gastric emptying. Do not administer with drugs that alter gastrointestinal motility (e.g., anticholinergic agents such as atropine) or that slow the intestinal absorption of nutrients (e.g., α–glucosidase inhibitors). SYMLIN has the potential to delay the absorption of concomitantly administered oral medications; if rapid onset is a critical determinant of effectiveness (such as analgesics), the agent should be administered at least 1 hour prior to or 2 hours after SYMLIN injection.

Pregnant and Nursing Women: No adequate and well-controlled studies have been conducted in pregnant women. It is unknown whether SYMLIN is excreted in human milk. SYMLIN should only be used in pregnancy or while nursing if the potential benefit justifies the potential risk.

EFFICACY - TYPE 1 DIABETES

SYMLIN plus insulin reduced A1C, weight, and mealtime insulin requirements in adults with type 1 diabetes at 6 months compared with placebo plus insulin*7-9

Mean change in A1C (Primary endpoint)

Statistically significant reduction compared with placebo (P <0.05).

Mean change in weight

SYMLIN is not indicated for the management of obesity.

*Pooled analyses of 3 trials.

Mean change in rapid/short-acting insulin doses

ADVERSE EVENTS - TYPE 1 DIABETES

ADVERSE REACTIONS IN PATIENTS WITH TYPE 1 DIABETES1

Most common adverse events reported in ≥ 5% of patients treated with SYMLIN® (pramlintide acetate) injection plus insulin and with greater incidence than in patients treated with placebo plus insulin were:

Incidence of Severe Hypoglycemia in Patients With Type 1 Diabetes

  • Patient-ascertained hypoglycemia
  • Medically assisted hypoglycemia

Patient-ascertained severe hypoglycemia: Requiring the assistance of another individual (including aid in ingestion of oral carbohydrate); and/or requiring the administration of glucagon injection, IV glucose, or other medical intervention.

Medically assisted severe hypoglycemia: Requiring glucagon, IV glucose, hospitalization, paramedic assistance, emergency room visit, and/or assessed as an SAE by the investigator.

Pooled analysis from three (one 26-week, two 52-week) phase 3, double-blind, randomized, placebo-controlled, parallel-group multicenter trials evaluated the efficacy and safety of pramlintide plus insulin compared to insulin alone in patients with type 1 diabetes mellitus and inadequate glycemic control.


EFFICACY - TYPE 2 DIABETES

SYMLIN plus insulin reduced A1C, weight, and mealtime insulin requirements in adults with type 2 diabetes at 6 months compared with placebo plus insulin*1,7,10

Mean change in A1C (Primary endpoint)

Statistically significant reduction compared with placebo (P <0.05).

Mean change in weight

SYMLIN is not indicated for the management of obesity.

*Pooled analyses of 2 trials.

Mean change in rapid/short-acting insulin doses

ADVERSE EVENTS - TYPE 2 DIABETES

ADVERSE REACTIONS IN PATIENTS WITH TYPE 2 DIABETES

Most common adverse events reported in ≥ 5% of patients treated with SYMLIN® (pramlintide acetate) injection plus insulin and with greater incidence than in patients treated with placebo plus insulin were:

Incidence of Severe Hypoglycemia in Patients With Type 2 Diabetes

  • Patient-ascertained hypoglycemia
  • Medically assisted hypoglycemia

Patient-ascertained severe hypoglycemia: Requiring the assistance of another individual (including aid in ingestion of oral carbohydrate); and/or requiring the administration of glucagon injection, IV glucose, or other medical intervention.

Medically assisted severe hypoglycemia: Requiring glucagon, IV glucose, hospitalization, paramedic assistance, emergency room visit, and/or assessed as an SAE by the investigator.

DOSING AND ADMINISTRATION

General Administration Information1

SYMLINPen injector for type 1 or type 2 patients with diabetes using mealtime insulin and inadequately controlled on optimized insulin therapy

  • SYMLIN® (pramlintide acetate) injection dosage differs depending on whether the patient has type 1 or type 2 diabetes
  • SYMLIN should be stored in the refrigerator until it is ready to be used. SYMLIN should be at room temperature before injecting to reduce potential injection site reactions
  • SYMLIN injection should be administered subcutaneously immediately prior to each major meal (≥250 kcal or containing ≥30 g of carbohydrate)
  • Each SYMLIN dose should be administered subcutaneously into the abdomen or thigh (administration into the arm is not recommended because of variable absorption). Injection sites should be rotated and should be distinct from the site chosen for any concomitant insulin injection

SYMLIN and insulin

  • SYMLIN and insulin should always be administered as separate injections
  • SYMLIN should not be mixed with any type of insulin
  • If a SYMLIN dose is missed, wait until the next scheduled dose and administer the usual amount. When initiating therapy with SYMLIN, initial insulin dose reduction is required in all patients to reduce the risk of insulin-induced severe hypoglycemia
  • Insulin dose adjustments should be made only as directed by the healthcare professional
  • Patients should be monitored at regular intervals to assess SYMLIN tolerability and its effect on blood glucose, so that individualized insulin adjustments can be initiated

WARNINGS

Proper patient selection is critical to safe and effective use of SYMLIN: Review HbA1c, recent blood glucose monitoring data, history of insulin-induced hypoglycemia, current insulin regimen, and body weight before initiation of therapy. Only consider SYMLIN for 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 insulin-use and supported by a diabetes educator

Do NOT consider SYMLIN for patients meeting any of the following criteria:

  • poor compliance with current insulin regimen
  • poor compliance with prescribed self-blood glucose monitoring
  • HbA1c >9%
  • recurrent severe hypoglycemia requiring assistance during the past 6 months
  • presence of hypoglycemia unawareness
  • confirmed diagnosis of gastroparesis
  • require the use of drugs that stimulate gastrointestinal motility
  • pediatric patients

Initiating and Titrating SYMLIN Dose1

Dosing titration for patients with type 1 diabetes
Administer SYMLIN subcutaneously immediately prior to major meals.

MEALTIME INSULIN*: When starting SYMLIN® (pramlintide acetate) injection, initially decrease insulin dose by 50%. Monitor blood glucose levels frequently (pre- and post-meals and at bedtime) and adjust insulin doses accordingly to optimize glycemic control.

*Mealtime insulin = Preprandial, rapid-acting, short-acting, fixed-mixed insulins (eg, 70/30).

Dosing titration for patients with type 2 diabetes
Administer SYMLIN subcutaneously immediately prior to major meals.

MEALTIME INSULIN*: When starting SYMLIN, initially decrease insulin dose by 50%. Monitor blood glucose levels frequently (pre- and post-meals and at bedtime) and adjust insulin doses accordingly to optimize glycemic control.

*Mealtime insulin = Preprandial, rapid-acting, short-acting, fixed-mixed insulins (eg, 70/30).

Managing insulin dose after SYMLIN initiation

  • After the initial 50% reduction in mealtime insulin dose, individualize insulin dose adjustments based on glycemic control.
  • An increased frequency of mild to moderate hypoglycemia should be viewed as a warning sign of increased risk for severe hypoglycemia.

Discontinuation of therapy

SYMLIN therapy should be discontinued if any of the following occur

  • Recurrent unexplained hypoglycemia that requires medical assistance;
  • Persistent clinically significant nausea;
  • Noncompliance with self-monitoring of blood glucose concentrations;
  • Noncompliance with insulin dose adjustments;
  • Noncompliance with scheduled healthcare professional contacts or recommended clinic visits.

IMPORTANT SAFETY INFORMATION

WARNING: SEVERE HYPOGLYCEMIA
SYMLIN is used with insulin and has been associated with an increased risk of insulin induced severe hypoglycemia, particularly in patients with type 1 diabetes. When severe hypoglycemia associated with SYMLIN use occurs, it is seen within 3 hours following a SYMLIN injection. If severe hypoglycemia occurs while operating a motor vehicle, heavy machinery, or while engaging in other high-risk activities, serious injuries may occur. Appropriate patient selection, careful patient instruction, and insulin dose adjustments are critical elements for reducing this risk.
Click here for additional Important Safety Information.

CONTRAINDICATIONS

  • Known hypersensitivity to SYMLIN or any of its components, including metacresol
  • Confirmed diagnosis of gastroparesis
  • Hypoglycemia unawareness

WARNINGS

Proper patient selection is critical to safe and effective use of SYMLIN: Review HbA1c, recent blood glucose monitoring data, history of insulin-induced hypoglycemia, current insulin regimen, and body weight before initiation of therapy. Only consider SYMLIN for 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 insulin-use and supported by a diabetes educator

Do NOT consider SYMLIN for patients meeting any of the following criteria:

  • poor compliance with current insulin regimen
  • poor compliance with prescribed self-blood glucose monitoring
  • HbA1c >9%
  • recurrent severe hypoglycemia requiring assistance during the past 6 months
  • presence of hypoglycemia unawareness
  • confirmed diagnosis of gastroparesis
  • require the use of drugs that stimulate gastrointestinal motility
  • pediatric patients

Hypoglycemia: SYMLIN (pramlintide acetate) alone does not cause hypoglycemia. However, SYMLIN is indicated to be co-administered with insulin therapy and in this setting SYMLIN increases the risk of insulin-induced severe hypoglycemia, particularly in patients with type 1 diabetes. Severe hypoglycemia associated with SYMLIN occurs within the first 3 hours following a SYMLIN injection. Serious injuries may occur if severe hypoglycemia occurs while operating a motor vehicle, heavy machinery, or while engaging in other high-risk activities.
Therefore, when introducing SYMLIN therapy, appropriate precautions need to be taken to avoid increasing the risk for insulin-induced severe hypoglycemia. These precautions include frequent pre- and post-meal glucose monitoring combined with an initial 50% reduction in pre-meal doses of short-acting insulin. The addition of any antihyperglycemic agent such as SYMLIN to an existing regimen of one or more antihyperglycemic agents (e.g., insulin, sulfonylurea), or other agents that can increase the risk of hypoglycemia may necessitate further insulin dose adjustments; closely monitor blood glucose.

PRECAUTIONS

Never mix SYMLIN and insulin: Administer as separate injections. Mixing can alter the pharmacokinetics of both products.

Allergy: Local allergies such as redness, swelling, or itching at the site of injection may occur. The incidence of systemic allergic reactions was 5% for SYMLIN plus insulin vs. 4%-5% for placebo plus insulin.

Drug Interactions: SYMLIN slows gastric emptying. Do not administer with drugs that alter gastrointestinal motility (e.g., anticholinergic agents such as atropine) or that slow the intestinal absorption of nutrients (e.g., α–glucosidase inhibitors). SYMLIN has the potential to delay the absorption of concomitantly administered oral medications; if rapid onset is a critical determinant of effectiveness (such as analgesics), the agent should be administered at least 1 hour prior to or 2 hours after SYMLIN injection.

Pregnant and Nursing Women: No adequate and well controlled studies have been conducted in pregnant women. It is unknown whether SYMLIN is excreted in human milk. SYMLIN should only be used in pregnancy or while nursing if the potential benefit justifies the potential risk.

ADVERSE REACTIONS

Most common adverse events reported in ≥ 5% of patients treated with SYMLIN plus insulin and with greater incidence than in patients treated with placebo plus insulin were:

  • Type 2 Diabetes: nausea (28% vs. 12%), headache (13% vs. 7%), anorexia (9% vs. 2%), vomiting (8% vs. 4%), abdominal pain (8% vs. 7%), fatigue (7% vs. 4%), dizziness (6% vs. 4%), coughing (6% vs. 4%), pharyngitis (5% vs. 2%).
  • Type 1 Diabetes: nausea (48% vs. 17%), anorexia (17% vs. 2%), inflicted injury (14% vs. 10%), vomiting (11% vs. 7%), arthralgia (7% vs. 5%), fatigue (7% vs. 4%), allergic reaction (6% vs. 5%), dizziness (5% vs. 4%).

The incidence for severe hypoglycemic adverse events in placebo-controlled trials with SYMLIN plus insulin vs. placebo plus insulin and with greater incidence than in patients treated with placebo plus insulin were:

  • Type 2 Diabetes: Patient-ascertained severe hypoglycemia at 0-3 months (8.2% vs. 2.1%) and at >3-6 months (4.7% vs. 2.4%). Medically assisted severe hypoglycemia at 0-3 months (1.7% vs. 0.7%).
  • Type 1 Diabetes: Patient-ascertained severe hypoglycemia at 0-3 months (16.8% vs. 10.8%) and at >3-6 months (11.1% vs. 8.7%). Medically assisted severe hypoglycemia at 0-3 months (7.3% vs. 3.3%) and at >3-6 months (5.2% vs. 4.3%).

References: 1. SYMLIN [package insert]. San Diego, CA: Amylin Pharmaceuticals, LLC; 2012.  2. Kruger DF, Gatcomb PM, Owen SK. Clinical implications of amylin and amylin deficiency. Diabetes Educ. 1999;25(3):389-397. 3. Edelman S, Weyer C. Unresolved challenges with insulin therapy in type 1 and type 2 diabetes: potential benefit of replacing amylin, a second β–cell hormone. Diabetes Tech Ther. 2002;4(2): 175-189. 4. Weyer C, Gottlieb A, Kim D, et al. Pramlintide reduces postprandial glucose excursions when added to regular insulin or insulin lispro in subjects with type 1 diabetes. Diabetes Care. 2003;26 (11):3074-3079. 5. Maggs DG, Fineman M, Kornstein J, et al. Pramlintide reduces postprandial glucose excursions when added to insulin lispro in subjects with type 2 diabetes: a dose-timing study. Diabetes Metab Res Rev. 2004;20(1):55-60. 6. Karl D, Philis-Tsimikas A, Darsow T, et al. Pramlintide as an adjunct to insulin in patients with type 2 diabetes in a clinical practice setting reduced A1C, postprandial glucose excursions, and weight. Diabetes Technol Ther. 2007;9(2):191-199. 7. Data on file [PRAM 001]. Amylin Pharmaceuticals, LLC. San Diego, CA. 8. Whitehouse F, Kruger D, Fineman M, et al. A randomized study and open-label extension evaluating the long-term efficacy of pramlintide as an adjunct to insulin therapy in type 1 diabetes. Diabetes Care. 2002;25(4):724-730. 9. Ratner R, Dickey R, Fineman M, et al. Amylin replacement with pramlintide as an adjunct to insulin therapy improves long-term glycaemic and weight control in Type 1 diabetes mellitus: a 1-year, randomized controlled trial. Diabet Med. 2004;24(1):1204-1212. 10. Hollander P, Levy P, Fineman M, et al. Pramlintide as an adjunct to insulin therapy improves long-term glycemic and weight control in patients with type 2 diabetes. Diabetes Care. 2003;26(3):784-790.