Symlin

Aka: Symlin, Pramlintide, Amylinomimetic, Amylin Analogue

1. Indications
   1. Type I and II Diabetes Mellitus
      1. Adjunct to Insulin therapy
      2. Third-line measure due to Hypoglycemia risk and cost
2. Contraindications
   1. Gastroparesis
3. Mechanism
   1. Pramlintide is a synthetic analogue of human Amylin
   2. Amylin is secreted with Insulin from Pancreas
   3. Amylin lowers post-prandial Blood Sugars
      1. Delays gastric emptying
      2. Inhibits glucago release
4. Dosing
   1. Protocol
      1. Reduce short and mixed-acting Insulin dose by 50%
      2. Use 100 unit 0.3 ml syringe
      3. Take with at least 250 calories (>30 g Carbohydrate)
   2. Type I Diabetes Mellitus
      1. Start: 15 mcg (2.5 U) SQ tid immediately before meals
      2. Titrated in 15 mcg increments q3-7 days
      3. Target: 30-60 mcg (5-10 units) SQ tid before meals
      4. Discontinue if significant Nausea
   3. Type II Diabetes Mellitus
      1. Start: 60 mcg (10 U) SQ tid immediately before meals
      2. Target: 60-120 mcg (10-20 units) SQ tid before meals
      3. Discontinue if significant Nausea
5. Precautions
   1. Switch to new pen device which replaces the vials and prevents dosing errors
      1. Warning: Pen concentration is different than vial concentration
   2. Dosing errors are common with the vials
      1. Dosing is typically listed in mcg, but is drawn up in Insulin syringes marked with units
      2. A patient who mistakes their 30 mcg dose for 30 units is accidentally taking 180 mcg
6. Adverse effects
   1. Nausea (28%) or Vomiting (8%): Especically Type I DM (related to Delayed Gastric Emptying)
      1. Contraindicated in Gastroparesis
   2. Headache (13%)
   3. Anorexia (9%)
   4. Abdominal Pain (8%)
   5. Severe Hypoglycemia (4.7%)
      1. Occurs 3 hours after Insulin and Pramlintide dose
      2. FDA Black box warning (decrease Insulin dose before starting)
7. Advantages
   1. Lowers weight 3 lb or 1.4 kg (Placebo: 0.6 kg gained)
8. Disadvantages
   1. Nausea
   2. Severe Hypoglycemia (FDA black box warning)
   3. No good longterm outcome data (other agents with better longterm efficacy are preferred)
   4. Expensive (>$1000)
9. Efficacy
   1. Drops A1C 0.5 to 0.6% (contrast with Placebo: 0.25% )
10. References
    1. Jones (2007) Am Fam Physician 75:1831-5 [PubMed]
    2. Kruger (2004) Drugs 64: 1419-32 [PubMed]
    3. Kleppinger (2003) Ann Pharmacother 37:1082-9 [PubMed]
    4. Ryan (2005) Clin Ther 27:1500-12 [PubMed]
    5. Steinberg (2019) Am Fam Physician 99(4): 237-43 [PubMed]