Pramlintide in the treatment of type 1 and type 2 diabetes mellitus

Ryan, Gina J.; Jobe, Lynetta J.; Martin, Rhonda

doi:10.1016/j.clinthera.2005.10.009

Cited by 138 publications

(124 citation statements)

References 32 publications

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“…In this study, the average plasma glucose concentration was about 10 mM (SD=5.2); thus, the permissive effect of glucose to accelerate gastric emptying might be negligible in this study. In addition to regulating the rate of gastric emptying after meals, pramlintide complements insulin effects by targeting postprandial glucagon excess, resulting in improved postprandial glucose control in diabetic patients (40). Failure to restore the normal glucagon/insulin ratio in the portal vein may in part contribute to the fact that many insulin-treated patients continue experiencing problems of postprandial hyperglycemia (41).…”

Section: Discussionmentioning

confidence: 99%

Study Reanalysis Using a Mechanism-Based Pharmacokinetic/Pharmacodynamic Model of Pramlintide in Subjects with Type 1 Diabetes

Fang

Landersdorfer

Cirincione³

et al. 2012

AAPS J

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Abstract. This report describes a pharmacokinetic/pharmacodynamic model for pramlintide, an amylinomimetic, in type 1 diabetes mellitus (T1DM). Plasma glucose and drug concentrations were obtained following bolus and 2-h intravenous infusions of pramlintide at three dose levels or placebo in 25 T1DM subjects during the postprandial period in a crossover study. The original clinical data were reanalyzed by mechanism-based population modeling. Pramlintide pharmacokinetics followed a twocompartment model with zero-order infusion and first-order elimination. Pramlintide lowered overall postprandial plasma glucose AUC (AUC net ) and delayed the time to peak plasma glucose after a meal (T max ). The delay in glucose T max and reduction of AUC net indicate that overall plasma glucose concentrations might be affected by differing mechanisms of action of pramlintide. The observed increase in glucose T max following pramlintide treatment was independent of dose within the studied dose range and was adequately described by a dose-independent, maximum pramlintide effect on gastric emptying of glucose in the model. The inhibition of endogenous glucose production by pramlintide was described using a sigmoidal function with capacity and sensitivity parameter estimates of 0.995 for I max and 23.8 pmol/L for IC 50 . The parameter estimates are in good agreement with literature values and the IC 50 is well within the range of postprandial plasma amylin concentrations in healthy humans, indicating physiological relevance of the pramlintide effect on glucagon secretion in the postprandial state. This model may prove to be useful in future clinical studies of other amylinomimetics or antidiabetic drugs with similar mechanisms of action.

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Section: Discussionmentioning

confidence: 99%

Study Reanalysis Using a Mechanism-Based Pharmacokinetic/Pharmacodynamic Model of Pramlintide in Subjects with Type 1 Diabetes

Fang

Landersdorfer

Cirincione³

et al. 2012

AAPS J

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“…The effect of amylinbased therapy as measured by HbA1c lowering is modest (Ratner et al 2004). Consequently, amylin has been approved as adjunctive therapy with insulin for patients who have not achieved glycemic control with insulin monotherapy (Ryan et al 2005;Weyer et al 2001). Amylin decreases body weight in both diabetics and nondiabetics and is currently being investigated for its antiobesity potential (Inzucchi and McGuire 2008;Sadry and Drucker 2013).…”

Section: Current Treatments For Diabetesmentioning

confidence: 99%

Current and Emerging Treatment Options in Diabetes Care

et al. 2015

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Diabetes constitutes an increasing threat to human health, particularly in newly industrialized and densely populated countries. Type 1 and type 2 diabetes arise from different etiologies but lead to similar metabolic derangements constituted by an absolute or relative lack of insulin that results in elevated plasma glucose. In the last three decades, a set of new medicines built upon a deeper understanding of physiology and diabetic pathology have emerged to enhance the clinical management of the disease and related disorders. Recent insights into insulin-dependent and insulin-independent molecular events have accelerated the generation of a series of novel medicinal agents, which hold the promise for further advances in the management of diabetes. In this chapter, we provide a historical context for what has been accomplished to provide perspective for future research and novel emerging treatment options.

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“…However, tolerability can limit its usefulness. Studies have found that 9.5-59 % of patients reported mild nausea and 0.7-8.5 % experienced severe nausea with pramlintide [58]. Perhaps the most significant limitation for the widespread use of pramlintide in T1DM is its mechanism of delivery.…”

Section: Pramlintidementioning

confidence: 98%

“…Pramlintide is FDA-approved for use with prandial insulin in patients with T1DM. Activation of amylin receptors in the brain decreases food intake and slows gastrointestinal mobility [58]. In addition, amylin suppresses postprandial release of glucagon from pancreatic α-cells by a neurohormonal mechanism [59].…”

Section: Pramlintidementioning

confidence: 99%

Management of Severe Insulin Resistance in Patients with Type 1 Diabetes

Schechter¹,

Reutrakul

2015

Curr Diab Rep

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Managing severe insulin resistance (IR) in patients with type 1 diabetes (T1DM) can be challenging for both clinicians and patients. As average weight for patients with T1DM has increased in recent decades, IR in this population has become more widespread. Currently, almost 50 % of patients with T1DM are overweight or obese. While intensive insulin therapy is associated with reduction in complications, aggressive treatment can lead to weight gain. With increasing weight, insulin can become less effective to control glycemia, resulting in higher insulin doses and hence more weight gain. Novel strategies to break this vicious cycle are needed. This review will investigate current research on insulin formulations, lifestyle modification, adjunct therapies, and surgery that may help better manage patients with T1DM and IR.

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Pramlintide in the treatment of type 1 and type 2 diabetes mellitus

Cited by 138 publications

References 32 publications

Study Reanalysis Using a Mechanism-Based Pharmacokinetic/Pharmacodynamic Model of Pramlintide in Subjects with Type 1 Diabetes

Study Reanalysis Using a Mechanism-Based Pharmacokinetic/Pharmacodynamic Model of Pramlintide in Subjects with Type 1 Diabetes

Current and Emerging Treatment Options in Diabetes Care

Management of Severe Insulin Resistance in Patients with Type 1 Diabetes

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