Efficacy and safety of exenatide once weekly versus sitagliptin or pioglitazone as an adjunct to metformin for treatment of type 2 diabetes (DURATION-2): a randomised trial.

Background: Most patients with type 2 diabetes begin pharmacotherapy with metformin, but eventually need additional treatment. We assessed the safety and efficacy of once weekly exenatide, a glucagon-like peptide 1 receptor agonist, versus maximum approved doses of the dipeptidyl peptidase-4 inhibitor, sitagliptin, or the thiazolidinedione, pioglitazone, in patients treated with metformin.

Methods: In this 26-week randomised, double-blind, double-dummy, superiority trial, patients with type 2 diabetes who had been treated with metformin, and at baseline had mean glycosylated haemoglobin (HbA(1c)) of 8.

DURATION-1: exenatide once weekly produces sustained glycemic control and weight loss over 52 weeks.

Objective: In the Diabetes Therapy Utilization: Researching Changes in A1C, Weight and Other Factors Through Intervention with Exenatide Once Weekly (DURATION-1) study, the safety and efficacy of 30 weeks of treatment with the glucagon-like peptide-1 receptor agonist exenatide once weekly (exenatide QW; 2 mg) was compared with exenatide BID in 295 patients with type 2 diabetes. We now report the safety and efficacy of exenatide QW in 1) patients who continued treatment for an additional 22 weeks (52 weeks total) and 2) patients who switched from exenatide BID to exenatide QW after 30 weeks.

Research Design And Methods: In this randomized, multicenter, comparator-controlled, open-label trial, 258 patients entered the 22-week open-ended assessment phase (n = 128 QW-only; n = 130 BID-->QW).

Randomized comparison of pramlintide or mealtime insulin added to basal insulin treatment for patients with type 2 diabetes.

Objective: To compare the efficacy and safety of adding mealtime pramlintide or rapid-acting insulin analogs (RAIAs) to basal insulin for patients with inadequately controlled type 2 diabetes.

Research Design And Methods: In a 24-week open-label, multicenter study, 113 patients were randomly assigned 1:1 to addition of mealtime pramlintide (120 microg) or a titrated RAIA to basal insulin and prior oral antihyperglycemic drugs (OADs). At screening, patients were insulin naive or had been receiving <50 units/day basal insulin for <6 months.

Exenatide once weekly for the treatment of type 2 diabetes.

Exenatide is the first glucagon-like peptide-1 (GLP-1) receptor agonist approved for the treatment of type 2 diabetes mellitus (T2DM). Exenatide lowers blood glucose through multiple mechanisms, including enhancement of glucose-dependent insulin secretion, suppression of excess glucagon secretion, reduction of food intake and slowing of gastric emptying. The current formulation of exenatide requires twice-daily dosing (exenatide BID), and an extended-release formulation of exenatide is now in development for use as a once-weekly injection (exenatide QW).

Pramlintide in the treatment of diabetes mellitus.

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.

Effect of pramlintide as an adjunct to basal insulin on markers of cardiovascular risk in patients with type 2 diabetes.

Objective: Intensification of insulin therapy in patients with type 2 diabetes, while improving glycemic control, often leads to an increase in body weight and other markers of cardiovascular risk. The effects of pramlintide as an adjunct to basal insulin titration (without mealtime insulin) on glycemia and cardiovascular risk markers were examined.

Research Design And Methods: This was a post hoc analysis of a 16-week, double-blind, placebo-controlled study in patients with type 2 diabetes (N = 211) using insulin glargine (without mealtime insulin) +/- oral agents.