Pharmacology Update
Pramlintide Acetate Injection (Symlin.)
By William T. Elliott, MD,
FACP, and James Chan, PharmD, PhD
Dr. Elliott is Chair, Formulary Committee, Northern California Kaiser Permanente; Associate Clinical Professor of Medicine, University of California, San Francisco; Dr. Chan is Pharmacy Quality and Outcomes Manager, Kaiser Permanente, Oakland, CA.
Drs. Chan and Elliott report no financial relationships to this field of study.
A synthetic analog of human amylin has been approved for the treatment of type 1 and type 2 diabetics.
Pramlintide is a 37-amino acid peptide which differs from human amylin with substitution of three amino acids at positions 25, 28, and 29. It represents the first of a new class of "amylinomimetic" antidiabetic compounds. It is marketed by Amylin Pharmaceuticals, Inc as Symlin®.
Indications
Pramlintide is approved for the treatment of type 1 diabetics who have failed to achieve desired glucose control despite optimal insulin therapy. It is also approved for type 2 diabetics who have failed to achieve glucose control despite optimal insulin therapy, with or without a concurrent sulfonylurea or motorman.1
Dosage
For type 1 diabetes, the initial dose is 15 µg given subcutaneously immediately before major meals. The dose may be titrated at 15 mg increments to a maintenance dose of 30 µg or 60 µg.
For type 2 diabetics, the initial dose is 60 µg immediately before major meals and may be increased to 120 µg. Short or rapid acting insulin should be reduced by about 50% and blood glucose should be monitored pre and post meals and at bedtime.1 Once the target dose of pramlintide has been established, insulin dose should be adjusted to optimized glycolic control.
Pramlintide is supplied as a 5 mL vial containing 50 60 µg doses.
Potential Advantages
Pramlintide provides a drug with a different mechanism of action for the management of both type 1 and type 2 diabetes. Weight loss has been reported with treatment.2-5
Potential Disadvantages
Pramlintide must be given in multiple injections each day. Severe hypoglycemia has been reported, particularly in type 1 diabetics. Improvement in glycemic control (ie, HbA1c) is modest and the benefit appears to decline over time following maximum response at 13 weeks.2-4 The most frequent adverse event is nausea. The cost of pramlintide is $90 to $180 per month.
Comments
Amylin is a peptide hormone co-secreted with insulin from the pancreatic beta cells. Its actions include inhibition of glucagon secretion, delay of gastric emptying, and reducing satiety.2 Pramlintide is an analog of amylin that can be administered subcutaneously with similar physiological effects.3 In clinical studies, pramlintide reduced HbA1c by a placebo subtracted difference of 0.4% at 6 months in type 2 patients and 0.33% in type 1 patients .1 The greatest improvement was observed at 13 weeks with decreases in improvement over time.2,4 A similar pattern of weight loss was also observed. Changes in weight of -0.3 to -0.6 for type 1 patients and -0.5 to -1.4 for type 2 patients were observed in 1-year clinical trials.2-5 Weight reduction was greater in overweight and obese patients. Postprandial glucose lowering with pramlintide has been associated with reduction in postprandial oxidative stress.6 Pramlintide costs $1.60 per 60 mg dose. Severe hypoglycemia has been associated with concomitant insulin use especially in type 1 patients. It is generally seen within the 3 hours after injection. Nausea is a common adverse event and again more prevalent in type 1 patients.3 This appears to be dose dependent and attenuates over time.
Clinical Implications
Pramlintide is yet another drug with a new mechanism of action for the treatment of diabetes. It is recommended for use with insulin. In the clinical studies, the dose of insulin is fixed or little adjustment permitted. Thus it is difficult to assess the benefit of pramlintide in a more real life setting where patients are encouraged to adjust their insulin doses. Given the rather modest improvement in HbA1c and the risk of severe hypoglycemia the role of this new drug remains to be determined.
References
1. Symlin Product Information. Amylin Pharmaceuticals, Inc. March 2005.
2. Schmitz O, et al. Amylin agonists: a novel approach in the treatment of diabetes. Diabetes. 2004;53(Suppl 3):S233-S238.
3. Kruger DF, Gloster MA. Pramlintide for the treatment of insulin-requiring diabetes mellitus: rationale and review of clinical data. Drugs. 2004;64:1419-1432.
4. Whitehouse, F, 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;25:724-730.
5. Ratner RE 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;21:1204-1212.
6. Ceriello A et al. Effects of pramlintide on postprandial glucose excursions and measures of oxidative stress in patients with type 1 diabetes. Diabetes Care. 2005;28:632-637.
By William T. Elliott, MD, FACP, and James Chan, PharmD, PhD Dr. Elliott is Chair, Formulary Committee, Northern California Kaiser Permanente; Associate Clinical Professor of Medicine, University of California, San Francisco; Dr. Chan is Pharmacy Quality and Outcomes Manager, Kaiser Permanente, Oakland, CA. Drs. Chan and Elliott report no financial relationships to this field of study. A synthetic analog of human amylin has been approved for the treatment of type 1 and type 2 diabetics. Pramlintide is a 37-amino acid peptide which differs from human amylin with substitution of three amino acids at positions 25, 28, and 29. It represents the first of a new class of amylinomimetic antidiabetic compounds. It is marketed by Amylin Pharmaceuticals, Inc as Symlin.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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