The effect of chronic twice daily exenatide treatment on β-cell function in new onset type 2 diabetes.

Objective: To determine the effect of chronic daily exenatide treatment on β-cell function in type 2 diabetes (T2DM).

Background: Glucagon-like peptide receptor agonists, such as exenatide, are commonly used to treat patients with T2DM. Drugs in this class are insulinotropic but lower blood glucose by multiple mechanisms such that effects on β-cell function can be difficult to discern by conventional measures.

Effects of exenatide on systolic blood pressure in subjects with type 2 diabetes.

Background: The majority of patients with type 2 diabetes mellitus have blood pressure (BP) exceeding the recommended value of <130/80 mm Hg. Optimal control of hyperglycemia and hypertension has been shown to reduce the incidence of macrovascular and microvascular complications due to diabetes. Treatment with the GLP-1 receptor agonist exenatide, previously demonstrated to reduce hemoglobin A(1C) and weight in subjects with type 2 diabetes, was associated with BP reduction in several studies.

The effect of exenatide re-exposure on safety and efficacy.

Exenatide, a synthetic peptide originally isolated from salivary secretions of Heloderma suspectum, like other subcutaneously injected peptides, can cause antibody formation. Despite that antibody formation has been observed in some patients, results from previous clinical trials have not shown safety and efficacy concerns in exenatide-naïve patients. The objective of this multicenter, open-label study was to investigate the response of anti-exenatide antibody formation and the incidence of immune-related and hypersensitivity reactions after exenatide re-exposure.

Reduced daily risk of glycemic variability: comparison of exenatide with insulin glargine.

Background: Conventional methods describing daily glycemic variability (i.e., standard deviation and coefficient of variation) do not express risk.

Exenatide exhibits dose-dependent effects on glycemic control over 12 weeks in Japanese patients with suboptimally controlled type 2 diabetes.

This study assessed the dose-dependent efficacy and safety of exenatide over 12 weeks in Japanese patients with type 2 diabetes suboptimally controlled despite therapeutic doses of sulfonylurea (SU), SU plus biguanide, or SU plus thiazolidinedione. Patients were randomly assigned to placebo (N = 40), 2.5 microg (N = 38), 5 microg (N = 37), or 10 microg (N = 38) exenatide administered subcutaneously twice daily (BID).

Efficacy and safety of exenatide in patients of Asian descent with type 2 diabetes inadequately controlled with metformin or metformin and a sulphonylurea.

Aims: To evaluate the efficacy of exenatide in Asian patients with type 2 diabetes (T2D) inadequately controlled with oral agents.

Methods: Patients taking metformin (MET) alone or with a sulphonylurea (SU) were randomly assigned to exenatide 5 microg then 10 microg twice-daily for 4 and 12 weeks, respectively, or placebo. The primary endpoint was baseline to endpoint HbA(1c) change.

Efficacy and tolerability of exenatide monotherapy over 24 weeks in antidiabetic drug-naive patients with type 2 diabetes: a randomized, double-blind, placebo-controlled, parallel-group study.

Background: Evaluation of exenatide monotherapy in patients with type 2 diabetes may be of clinical interest based on improvements in glycemic control and weight that have been reported with the use of exenatide in combination with oral antidiabetic agents.

Objective: The aim of this study was to evaluate the efficacy and tolerability of exenatide monotherapy in patients with type 2 diabetes naive to antidiabetic agents and whose disease was inadequately controlled with diet and exercise alone.

Methods: This 24-week, double-blind, placebo-controlled, parallel-group study was conducted at 23 centers across the United States, Puerto Rico, Romania, Russia, and India.

Efficacy and safety of exenatide administered before the two largest daily meals of Latin American patients with type 2 diabetes.

Objective: To evaluate whether exenatide administered before breakfast and dinner (BD) or before lunch and dinner (LD) provided similar glycemic control in Latin American patients with type 2 diabetes mellitus (T2DM) who consume a small breakfast.

Methods: In this open-label, 2-arm study, patients taking metformin, sulfonylureas, and/or thiazolidinediones were randomized to exenatide before BD or before LD (5-mug exenatide for 4 weeks, then 10-microg exenatide for 8 weeks). Treatment assignment was determined by a computer-generated random sequence using an interactive response system.

Quantifying the effect of exenatide and insulin glargine on postprandial glucose excursions in patients with type 2 diabetes.

In this report, we quantify the effects of exenatide and glargine on the relative contributions of fasting and postprandial glucose (PPG) excursion to overall hyperglycemia based on self-monitored blood glucose. After 26 weeks of treatment, insulin glargine reduced fasting glucose to a greater extent than exenatide without significant effect on PPG excursion. The principal effect of exenatide on hyperglycemia was mitigating the rise in PPG with moderate improvement on fasting glucose.

Effects of exenatide versus insulin analogues on weight change in subjects with type 2 diabetes: a pooled post-hoc analysis.

Background And Objective: In two previously reported multi-center, randomized, open-label, comparator (insulin) controlled trials in patients with type 2 diabetes sub-optimally controlled with metformin and a sulfonylurea, treatment with exenatide and insulin analogue therapy produced similar reductions in glycosylated hemoglobin A(1c) (A1C). However, treatment with exenatide was associated with a reduction in body weight while insulin analogue therapy was associated with weight gain. This analysis further characterizes the relative impact of commonly employed insulin analogues versus exenatide on weight change over a 6-month period.

Tolerability and efficacy of exenatide and titrated insulin glargine in adult patients with type 2 diabetes previously uncontrolled with metformin or a sulfonylurea: a multinational, randomized, open-label, two-period, crossover noninferiority trial.

Objective: This study was conducted to compare the efficacy and safety profiles of exenatide and insulin glargine therapy in patients with type 2 diabetes who had not achieved glucose control with metformin or sulfonylurea monotherapy.

Methods: This multinational, randomized, open-label, crossover noninferiority study compared the efficacy of exenatide 10 pg BID and insulin glargine QD (titrated targeting a fasting serum glucose (FSG) level < or =5.6 mmol/L) in patients with type 2 diabetes treated with a single oral antidiabetic agent.

Exploring the substitution of exenatide for insulin in patients with type 2 diabetes treated with insulin in combination with oral antidiabetes agents.

Objective: This 16-week study explored the safety of substituting exenatide for insulin in patients with type 2 diabetes using insulin in combination with oral antidiabetes agents.

Research Design And Methods: Successful maintenance of glycemic control was predefined as an A1C increase of < 0.5%.

The effect of adding exenatide to a thiazolidinedione in suboptimally controlled type 2 diabetes: a randomized trial.

Background: Exenatide therapy is effective in combination with metformin or sulfonylureas for treating type 2 diabetes. Thiazolidinediones (TZDs) also are commonly used, but the efficacy of exenatide with a TZD has not been reported.

Objective: To compare the effects of exenatide versus placebo on glycemic control.

A comparison of twice-daily exenatide and biphasic insulin aspart in patients with type 2 diabetes who were suboptimally controlled with sulfonylurea and metformin: a non-inferiority study.

Aims/hypothesis: The aim of this 52-week, open-label, non-inferiority trial was to compare the safety and efficacy of exenatide (an incretin mimetic) with that of biphasic insulin aspart.

Materials And Methods: Patients on metformin and a sulfonylurea were randomised to exenatide (n = 253; 5 microg twice daily for 4 weeks, 10 microg thereafter) or biphasic insulin aspart (n = 248; twice-daily doses titrated for optimal glucose control), while continuing with metformin and sulfonylurea treatment.

Results: Glycaemic control achieved with exenatide was non-inferior to that achieved with biphasic insulin aspart (mean+/-SEM, HbA(1c) change: exenatide -1.

Patient-reported outcomes in a trial of exenatide and insulin glargine for the treatment of type 2 diabetes.

Background: Patient-reported measures can be used to examine whether drug differences other than clinical efficacy have an impact on outcomes that may be important to patients. Although exenatide and insulin glargine appear to have similar efficacy for treatment of type 2 diabetes, there are several differences between the two treatments that could influence outcomes from the patient's perspective. The purpose of the current study was to examine whether the two drugs were comparable as assessed by patient-reported outcomes using data from a clinical trial in which these injectable medications were added to pre-existing oral treatment regimens.

Long-term effects of exenatide therapy over 82 weeks on glycaemic control and weight in over-weight metformin-treated patients with type 2 diabetes mellitus.

Aim: The ability of the incretin mimetic exenatide to improve glycaemic control and reduce body weight was assessed over 82 weeks in patients with type 2 diabetes failing to achieve glycaemic control with maximally effective doses of metformin.

Methods: In this interim 82-week analysis, 150 (total cohort) of an eligible population of 183 patients opted to continue exenatide treatment in an uncontrolled open-label extension of a 30-week double-blind, placebo-controlled trial. Of these, 92 patients (completer cohort) achieved 82 weeks of exenatide therapy.

Exenatide versus insulin glargine in patients with suboptimally controlled type 2 diabetes: a randomized trial.

Background: Physicians may use either insulin or exenatide injections for patients with type 2 diabetes mellitus who have poor glycemic control despite taking oral blood glucose-lowering drugs.

Objective: To compare effects of exenatide and insulin glargine on glycemic control in patients with type 2 diabetes mellitus that is suboptimally controlled with metformin and a sulfonylurea.

Design: 26-week multicenter, open-label, randomized, controlled trial.

Therapy focused on lowering postprandial glucose, not fasting glucose, may be superior for lowering HbA1c. IOEZ Study Group.

Objective: To compare the overall efficacy of combination therapies focused on fasting or postprandial blood glucose in patients with type 2 diabetes not adequately controlled with oral sulfonylurea agents alone.

Research Design And Methods: A total of 135 patients were randomly assigned for 3 months to 1 of 3 combination regimens with glyburide (G) that addressed postprandial blood glucose with insulin lispro (L+G), premeal blood glucose with metformin (M+G), or fasting blood glucose (FBG) with bedtime NPH insulin (NPH+G).

Results: At end point, HbA1c was significantly lower with all therapies (P = 0.

A randomized placebo-controlled trial of repaglinide in the treatment of type 2 diabetes.

Objective: The objective of the study was to assess the efficacy and safety of repaglinide compared with placebo in the treatment of patients with type 2 diabetes.

Research Design And Methods: This was a phase II multicenter, double-blind, placebo-controlled, randomized, dose-adjustment and maintenance trial. After screening and a 2-week washout period, 99 patients were randomized to receive either repaglinide (n = 66) or placebo (n = 33).

A comparison of premixed insulin preparations in elderly patients. Efficacy of 70/30 and 50/50 human insulin mixtures.

Objective: To compare the postprandial hyperglycemic response to a standard breakfast of two premixed humulin insulin mixtures, 50/50 (50% NPH human insulin and 50% regular human insulin) and 70/30 (70% NPH human insulin and 30% regular human insulin) in elderly non-insulin-dependent diabetes mellitus (NIDDM) patients.

Research Design And Methods: On two mornings, each patient (n = 20) consumed a standard breakfast after a single dose of 50/50 or 70/30 insulin (0.3 U/kg) was administered in a randomized crossover fashion.

Benefits and risks with glyburide and glipizide in elderly NIDDM patients.

Objective: To compare the efficacy, benefits, and risks of glyburide and glipizide in elderly patients with non-insulin-dependent diabetes mellitus (NIDDM).

Research Design And Methods: Twenty-one elderly outpatients (mean age 70 yr) were treated for 8 wk, after being dose-titrated to achieve a fasting plasma glucose (FPG) concentration of less than 7.8 mM with glyburide or glipizide in a randomized crossover trial.

The safety and efficacy of a controlled low-energy ('very-low-calorie') diet in the treatment of non-insulin-dependent diabetes and obesity.

We evaluated the safety and efficacy of a highly supplemented controlled low-energy (1764 kJ [420 kcal]) diet in the treatment of non-insulin-dependent diabetes and obesity. Six obese, diabetic women ranging from 143% to 297% of ideal body weight were studied in a metabolic ward for 48 days. The subjects ingested a weight-maintenance diet during an eight-day control period followed by 40 days of an experimental diet containing 1764 kJ (420 kcal) of a mixture of protein (43% of energy intake), carbohydrates (51%), and fat (6%), supplemented with minerals, trace elements, and vitamins.

Evaluation of a new radioimmunoassay for urinary albumin.

We have evaluated a new commercially available radioimmunoassay kit for albumin determination in urine. The assay is precise; within-run precision (CV) in the clinically significant ranges is 1.8-3.

Use of urinary C-peptide to estimate insulin secretion during starvation.

The usefulness of measurements of urinary C-peptide excretion in indirectly assessing integrated insulin secretion during starvation was studied in eight obese subjects during a 72-h fast. Blood and urine samples were collected at 12-h intervals for measurement of insulin and C-peptide immunoreactivity. After 60 h, serum insulin and plasma C-peptide levels declined 47% and 37%, respectively, and the values were highly correlated (r = 0.