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Pramlintide

CAT#
10-101-28
Synonyms/Alias
AC 0137; AC 137; Symlin; Tripro-Amylin; riproamylin; Pramlintide; LS-181996; LS181996; Amylin
CAS No.
151126-32-8
Sequence
Lys-c[Cys-Asn-Thr-Ala-Thr-Cys]-Ala-Thr-Gln-Arg-Leu-Ala-Asn-Phe-Leu -Val-His-Ser-Ser-Asn-Asn-Phe-Gly-Pro-Ile-Leu-Pro-Pro-Thr-Asn-Val-Gly -Ser-Asn-Thr-Tyr-NH2
M.W/Mr.
3949.4
Molecular Formula
C171H267N51O53S2
Source
Synthetic
Long-term Storage Conditions
−20°C
Application
Pramlintide (Symlin) has been approved by the FDA as a new injectable drug for diabetes (both type 1 and 2).
Description
Pramlintide is an analogue of amylin, a small peptide hormone that is released into the bloodstream by the β-cells of the pancreas along with insulin, after a meal. Like insulin, amylin is completely absent in individuals with Type I diabetes.
Areas of Interest
Diabetes

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Pramlintide is a synthetic version of the naturally occurring pancreatic peptide called amylin. Amylin and pramlintide have similar effects on lowering postprandial glucose, lowering postprandial glucagon and delaying gastric emptying. Pramlintide use in type 1 and insulin requiring type 2 diabetes mellitus (DM) is associated with modest reductions in HbA1c often accompanied by weight loss. Limited data show a neutral effect on blood pressure.

Pramlintide, the first member of a new class of drugs for the treatment of insulin-using patients with type 2 or type 1 diabetes mellitus, is an analog of the peptide hormone amylin. Amylin is co-secreted with insulin from pancreatic beta cells and acts centrally to slow gastric emptying, suppress postprandial glucagon secretion, and decrease food intake. These actions complement those of insulin to regulate blood glucose concentrations. Amylin is relatively deficient in patients with type 2 diabetes, depending on the severity of beta-cell secretory failure, and is essentially absent in patients with type 1 diabetes. Through mechanisms similar to those of amylin, pramlintide improves overall glycemic control, reduces postprandial glucose levels, and reduces bodyweight in patients with diabetes using mealtime insulin. Reductions in postprandial glucose and bodyweight are important, since postprandial hyperglycemia is associated with an increased risk of microvascular and macrovascular complications, and increased weight is an independent risk factor for cardiovascular disease. Pramlintide is generally well tolerated, with the most frequent treatment-emergent adverse event being mild to moderate nausea, which decreases over time. Pramlintide treatment is also associated with improvements in markers of oxidative stress and cardiovascular risk and improved patient-reported treatment satisfaction. These factors make pramlintide an attractive option for the treatment of postprandial hyperglycemia in patients with diabetes using mealtime insulin.

Edelman, S., Maier, H., & Wilhelm, K. (2008). Pramlintide in the treatment of diabetes mellitus. BioDrugs, 22(6), 375-386.

Amylin is a 37-amino acid peptide neurohormone that is cosecreted with insulin from the pancreatic beta cells in response to meals. It lowers serum glucose by decreasing glucagon release, slowing gastric emptying, and decreasing food intake. Pramlintide, a synthetic amylin analogue, is approved by the US Food and Drug Administration for use with mealtime insulin in patients with type 1 diabetes and patients with type 2 diabetes who are using mealtime insulin only or the combination of insulin and metformin and/or a sulfonylurea.

Ryan, G. J., Jobe, L. J., & Martin, R. (2005). Pramlintide in the treatment of type 1 and type 2 diabetes mellitus. Clinical therapeutics, 27(10), 1500-1512.

In patients with diabetes, dysregulation of multiple glucoregulatory hormones results in chronic hyperglycemia and an array of associated microvascular and macrovascular complications. Optimization of glycemic control, both overall (glycosylated hemoglobin [A1C]) and in the postprandial period, may reduce the risk of long-term vascular complications. However, despite significant recent therapeutic advances, most patients with diabetes are unable to attain and/or maintain normal or near-normal glycemia with insulin therapy alone. Pramlintide, an analog of amylin, is the first in a new class of pharmaceutical agents and is indicated as an adjunct to mealtime insulin for the treatment of patients with type 1 and type 2 diabetes. By mimicking the actions of the naturally occurring hormone amylin, pramlintide complements insulin by regulating the appearance of glucose into the circulation after meals via three primary mechanisms of action: slowing gastric emptying, suppressing inappropriate post-meal glucagon secretion, and increasing satiety. In long-term clinical trials, adjunctive pramlintide treatment resulted in improved postprandial glucose control and significantly reduced A1C and body weight compared with insulin alone. The combination of insulin and pramlintide may provide a more physiologically balanced approach to managing diabetes.

Pullman, J., Darsow, T., & Frias, J. P. (2006). Pramlintide in the management of insulin-using patients with type 2 and type 1 diabetes. Vascular health and risk management, 2(3), 203.

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