Pramlintide: Clinical Strategies for Success

Alrefai, Hisham; Latif, Kashif; Hieronymus, Laura; Weakley, Cindy R.; Moss, Robert J.

doi:10.2337/diaspect.23.2.124

Cited by 11 publications

(14 citation statements)

References 34 publications

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“…10,11 The first mechanism was disregarded because it is related to the amount of food consumed, not to the dynamics after ingestion. The second mechanism is pramlintide's action on EGP in which glucagon secretion is suppressed causing lowered EGP.…”

Section: Discussionmentioning

confidence: 99%

“…Pramlintide has 3 mechanisms: (1) modulates appetite, (2) suppresses glucagon secretion, and (3) slows the rate at which nutrients are delivered from the stomach to the small intestine for absorption. 10,11 The first mechanism was disregarded because it is related to the amount of food consumed, not to the dynamics after ingestion. The second mechanism is pramlintide's action on EGP in which glucagon secretion is suppressed causing lowered EGP.…”

Section: Discussionmentioning

confidence: 99%

“…Amylin mitigates the influx of endogenous and exogenous glucose into the circulation and thus improves the rate of glucose clearance incurred by insulin. 10,11 In T1DM however, both amylin and insulin production are decreased significantly due to the death of β-cells. Patients exhibit a paradoxical postprandial hyperglucagonemia in which endogenous glucagon levels are elevated in the portal circulation and insulin levels are reduced.…”

mentioning

confidence: 99%

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A Model of Glucose-Insulin-Pramlintide Pharmacokinetics and Pharmacodynamics in Type I Diabetes

Ramkissoon

Aufderheide

Bequette

et al. 2014

J Diabetes Sci Technol

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Type 1 diabetes mellitus (T1DM) is a chronic metabolic disorder characterized as an autoimmune disease in which the body specifically attacks pancreatic β-cells. This results in insulin and amylin deficiencies, which produces chronic hyperglycemia.1 Insulin injection therapy is effective in many patients, but it is imperfect. People with T1DM face a trade-off among glycemic control, lifestyle flexibility, and therapy effort. Using current therapy options, near normoglycemia can be achieved only by patients at the expense of lifestyle flexibility and increased therapy effort. Because of this excellent glycemic control remains more of an aspiration than a reality.Recent technological advances provide an opportunity to combine 3 technologies: continuous glucose monitors, insulin pumps, and a control algorithm; this forms the basis of an artificial pancreas. [2][3][4][5] Despite important advances in the artificial pancreas, most patients with T1DM are still unable to achieve near-normoglycemia with insulin therapy alone. The limitations of current insulin replacement therapy are especially evident during the postprandial period, when rapid and profound changes in glucose flux occur as a sudden appearance of meal-derived glucose goes into circulation. [6][7][8] In the development of an artificial pancreas, the primary difficulties are the inherent time delays in the closed system due to subcutaneous (SC) delivery of insulin and SC reading of glucose, with additional built-in filters in the monitor. The lack of timely information coupled with large postprandial excursions after a meal and poor insulin management make glucose regulation very difficult.2,8 Postprandial glucose control is the 1 area where the largest gain can be 517323D STXXX10.1177/1932296813517323Journal Abstract Background: Type 1 diabetes mellitus (T1DM) complications are significantly reduced when normoglycemic levels are maintained via intensive therapy. The artificial pancreas is designed for intensive glycemic control; however, large postprandial excursions after a meal result in poor glucose regulation. Pramlintide, a synthetic analog of the hormone amylin, reduces the severity of postprandial excursions by reducing appetite, suppressing glucagon release, and slowing the rate of gastric emptying. The goal of this study is to create a glucose-insulin-pramlintide physiological model that can be employed into a controller to improve current control approaches used in the artificial pancreas. Methods:A model of subcutaneous (SC) pramlintide pharmacokinetics (PK) was developed by revising an intravenous (IV) pramlintide PK model and adapting SC insulin PK from a glucose-insulin model. Gray-box modeling and least squares optimization were used to obtain parameter estimates. Pharmacodynamics (PD) were obtained by choosing parameters most applicable to pramlintide mechanisms and then testing using a proportional PD effect using least squares optimization. Results:The model was fit and validated using 27 data sets, which included placebo, PK, and PD d...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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A Model of Glucose-Insulin-Pramlintide Pharmacokinetics and Pharmacodynamics in Type I Diabetes

Ramkissoon

Aufderheide

Bequette

et al. 2014

J Diabetes Sci Technol

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“…During initial dosage titration, it may be helpful for patients to test blood glucose just prior to their meals and pramlintide dose and approximately 1 to 2 hours after their meals to determine how pramlintide may affect their blood glucose concentrations. 50 Continuous glucose monitoring (CGM) may help to define the impact of pramlintide on blood glucose levels and guide adjustments to insulin dosage when pramlintide is initiated 51,52 ; CGM data complement A1C assessments by providing insight into diurnal glucose fluctuations. Patients should be encouraged to monitor their blood glucose concentrations on an ongoing basis and modify treatment to accommodate variations in the timing and caloric content of meals as recommended by their health care providers.…”

Section: Rationale For Amylin Replacement In Type 1 and Type 2 Diabetesmentioning

confidence: 99%

“…Administering the first dose of pramlintide before an evening meal may allow patients to better manage symptoms of nausea (ie, they are typically at home and can evaluate how well they tolerate pramlintide). 50 Once the maintenance dose of pramlintide is reached, insulin dose adjustments can be made according to standard clinical practice based upon pre- and postprandial blood glucose. Note that the dose of pramlintide does not change from meal to meal; the same dose is taken immediately prior to major meals.…”

Section: Rationale For Amylin Replacement In Type 1 and Type 2 Diabetesmentioning

confidence: 99%

Role of Amylin in Type 1 and Type 2 Diabetes

Hieronymus

Griffin

2015

Diabetes Educ

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Amylin, formed primarily in pancreatic islet β cells, is cosecreted with insulin in response to caloric intake. Patients with type 1 diabetes have lower baseline amylin serum concentrations, and amylin response to caloric intake is absent. Patients with type 2 diabetes requiring insulin also have a diminished amylin response to caloric intake, potentially related to the degree of β-cell impairment. Key physiologic functions of amylin in maintaining glucose homeostasis include suppressing glucagon release in response to caloric intake, delaying the rate of gastric emptying, and stimulating the satiety center in the brain to limit caloric intake. Pramlintide is indicated for adults with type 1 and 2 diabetes who have not achieved adequate glucose control despite optimal insulin therapy. As an adjunct to insulin therapy, pramlintide demonstrated significant reductions in A1C in patients with type 1 and 2 diabetes, with favorable effects on body weight. It is administered subcutaneously before each major meal. There is an increased risk of hypoglycemia with insulin when used in combination with pramlintide. Other adverse effects may include nausea, vomiting, anorexia, reduced appetite, and headache. Proper patient selection and education are essential to successful pramlintide use.

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Managing weight and glycaemic targets in people with type 2 diabetes—How far have we come?

Blüher

Ceriello

Davies

et al. 2022

Endocrino Diabet & Metabol

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Introduction:As the vast majority of people with type 2 diabetes (T2D) are also overweight or obese, healthcare professionals (HCP) are faced with the task of addressing both weight management and glucose control. In this narrative review, we aim to identify the challenges of reaching and maintaining body weight targets in people with T2D and highlight current and future treatment interventions.Methods: A search of the PubMed database was conducted using the search terms "diabetes" and "weight loss."Results: According to emerging evidence, treating obesity may be antecedent to the development and progression of T2D. While clinical benefits typically set in upon achieving a weight loss of 3-5%, these benefits are progressive leading to further health improvements, and weight loss of >15% can have a disease-modifying effect in people with T2D, an outcome that up to recently could not be achieved with any blood glucose-lowering pharmacotherapy. However, advanced treatment options with weight-loss effects currently in development including the dual GIP/GLP-1 receptor agonists may enable simultaneous achievement of individual glycemic and weight goals. Conclusion:Despite considerable therapeutic progress, there is still a large unmet medical need in patients with T2D who miss their individualized glycemic and weightloss targets. Nonetheless, it is to be expected that development of future therapies and their use will favourably change the scenario of weight and glucose control in T2D.

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Pramlintide: Clinical Strategies for Success

Cited by 11 publications

References 34 publications

A Model of Glucose-Insulin-Pramlintide Pharmacokinetics and Pharmacodynamics in Type I Diabetes

A Model of Glucose-Insulin-Pramlintide Pharmacokinetics and Pharmacodynamics in Type I Diabetes

Role of Amylin in Type 1 and Type 2 Diabetes

Managing weight and glycaemic targets in people with type 2 diabetes—How far have we come?

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