Safety and Tolerability of Glucagon-Like Peptide-1 Receptor Agonists Utilizing Data from the Exenatide Clinical Trial Development Program.

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have demonstrated benefits for patients with type 2 diabetes including A1C reduction and weight loss with minimal risk of hypoglycemia. This article provides an evidence-based update of safety and tolerability considerations for the clinical use of GLP-1RAs as a class, with a specific detailed review of data from the exenatide clinical trial development program, which has the longest history and availability of safety and tolerability data as the first-approved GLP-1RA. Specific areas covered include comparative risk of hypoglycemia, as well as pancreatic, thyroid, and cardiovascular safety data; clinical guidance regarding current safety and tolerability data is also reviewed.

Optimizing treatment success with an amylin analogue.

Diabetes affects approximately 18 million adults in the United States. Diabetes increases the risk of microvascular and macrovascular complications, such as nerve neuropathy, retinopathy, nephropathy, and cardiovascular disease. Intensive diabetes management reduces the risk of complications but presents numerous challenges in clinical practice.

Pramlintide: A new tool in diabetes management.

The amylin analogue pramlintide acts in concert with insulin to regulate glucose metabolism. It reduces postprandial hyperglycemia by suppressing postprandial glucagon secretion, regulating gastric emptying, and reducing food intake. In clinical use, pramlintide reduces postprandial glycemic excursions and improves A(1c) without the weight gain and increased risk of hypoglycemia typically seen with intensification of diabetes therapy.

Overview of diabetes.

The number of people with diabetes is growing to epidemic proportions in the United States. There is a great deal of research on the evolving understanding of the pathogenesis of diabetes as compared to normoglycemia. The diagnostic criteria for diabetes have become streamlined to more appropriately and accurately diagnose the disease.

Impact of pramlintide on glucose fluctuations and postprandial glucose, glucagon, and triglyceride excursions among patients with type 1 diabetes intensively treated with insulin pumps.

Objective: To assess the effects of adjunctive treatment with pramlintide, an analog of the beta-cell hormone amylin, on 24-h glucose fluctuations and postprandial glucose, glucagon, and triglyceride excursions in patients with type 1 diabetes intensively treated with continuous subcutaneous insulin infusion (CSII).

Research Design And Methods: In this study, 18 patients (16 of whom could be evaluated) with type 1 diabetes (age 44 +/- 11 years, HbA(1c) 8.2 +/- 1.

Adjunctive therapy with the amylin analogue pramlintide leads to a combined improvement in glycemic and weight control in insulin-treated subjects with type 2 diabetes.

The objective of this study was to assess the effect of mealtime amylin replacement with pramlintide on long-term glycemic and weight control in subjects with type 2 diabetes. This 52-week, randomized, placebo-controlled, multicenter, double-blind, dose-ranging study in 538 insulin-treated subjects with type 2 diabetes compared the efficacy and safety of 30-, 75-, or 150-microg doses of pramlintide, a synthetic analogue of the beta-cell hormone amylin, to placebo when injected subcutaneously three times daily (TID) with major meals. Pramlintide therapy led to a mean reduction in HbA1c of 0.