Matthew Wintle

Exenatide effects on diabetes, obesity, cardiovascular risk factors and hepatic biomarkers in patients with type 2 diabetes treated for at least 3 years.

BACKGROUND Exenatide, an incretin mimetic for adjunctive treatment of type 2 diabetes (T2DM), reduced hemoglobin A(1c) (A1C) and weight in clinical trials. The objective of this study was to evaluate the effects of > or = 3 years exenatide therapy on glycemic control, body weight, cardiometabolic markers, and safety. METHODS Patients from three placebo-controlled trials and their open-label extensions were enrolled into one open-ended, open-label clinical trial. Patients were randomized to twice daily (BID) placebo, 5 mug exenatide, or 10 mug exenatide for 30 weeks, followed by 5 mug exenatide BID for 4 weeks, then 10 mug exenatide BID for > or = 3 years of exenatide exposure. Patients continued metformin and/or sulfonylureas. RESULTS 217 patients (64% male, age 58 +/- 10 years, weight 99 +/- 18 kg, BMI 34 +/- 5 kg/m(2), A1C 8.2 +/- 1.0% [mean +/- SD]) completed 3 years of exenatide exposure. Reductions in A1C from baseline to week 12 (-1.1 +/- 0.1% [mean +/- SEM]) were sustained to 3 years (-1.0 +/- 0.1%; p < 0.0001), with 46% achieving A1C < or = 7%. Exenatide progressively reduced body weight from baseline (-5.3 +/- 0.4 kg at 3 years; p < 0.0001). Patients with elevated serum alanine aminotransferase (ALT) at baseline (n = 116) had reduced ALT (-10.4 +/- 1.5 IU/L; p < 0.0001) and 41% achieved normal ALT. Patients with elevated ALT at baseline tended to lose more weight than patients with normal ALT at baseline (-6.1 +/- 0.6 kg vs. -4.4 +/- 0.5 kg; p = 0.03), however weight change was minimally correlated with baseline ALT (r = -0.01) or ALT change (r = 0.31). Homeostasis Model Assessment B (HOMA-B), blood pressure, and aspartate aminotransferase (AST) all improved. A subset achieved 3.5 years of exenatide exposure and had serum lipids available for analysis (n = 151). Triglycerides decreased 12% (p = 0.0003), total cholesterol decreased 5% (p = 0.0007), LDL-C decreased 6% (p < 0.0001), and HDL-C increased 24% (p < 0.0001). Exenatide was generally well tolerated. The most frequent adverse event was mild-to-moderate nausea. The main limitation of this study is the open-label, uncontrolled nature of the study design which does not provide a placebo group for comparison. CONCLUSION Adjunctive exenatide treatment for > or = 3 years in T2DM patients resulted in sustained improvements in glycemic control, cardiovascular risk factors, and hepatic biomarkers, coupled with progressive weight reduction.

Patient characteristics, drug adherence patterns, and hypoglycemia costs for patients with type 2 diabetes mellitus newly initiated on exenatide or insulin glargine

ABSTRACT Objective: Examine real-world effectiveness and hypoglycemia cost burden in patients with type 2 diabetes newly initiated on exenatide or insulin glargine. Design and methods: Retrospective cohort study describing patient characteristics, drug adherence patterns, and 1-year hypoglycemia rates with associated costs using an administrative claims database. Adult subjects with type 2 diabetes had an initial claim for exenatide or insulin glargine between May 1, 2005 and June 30, 2007, and had continuous eligibility for ≥ 6 months pre- and ≥ 12 months post-initiation. Results: The exenatide cohort (n = 3262) was 53 ± 10 years (±SD); 54% female. The insulin glargine cohort (n = 3038) was 56 ± 12 years; 41% female. The mean Deyo-Charlson comorbidity index score was 1.45 for exenatide versus 1.82 for insulin glargine (p < 0.001). Baseline OAD use rates for exenatide and insulin glargine, respectively, were 77% versus 69% metformin; 47% versus 65% sulfonylurea; 50% versus 49% thiazolidinedione; 56% versus 60% multiple OAD. For patients with two or more pharmacy claims for exenatide or insulin glargine, the 12-month medication possession ratio (MPR) was 68 ± 29% for exenatide and 58 ± 28% for insulin glargine (p < 0.001). MPR ≥ 80% was higher for exenatide (p < 0.001) and fewer patients discontinued therapy (p < 0.001). The probability of a hypoglycemic event was significantly lower for exenatide (p < 0.005), resulting in lower associated annual costs. Conclusions: This study provides the first real-world observational comparison of type 2 diabetes patients newly initiated on exenatide or insulin glargine. Exenatide patients had a lower comorbidity burden, better drug adherence, and a lower rate of hypoglycemic events with associated costs. Retrospective database analyses examine medical care utilization in large populations using a relatively inexpensive and expedient approach. However, data are only representative of a commercial health-care plan with limited information on multiple variables usually collected during clinical trials.

Pharmacokinetics of an Oral Drug (Acetaminophen) Administered at Various Times in Relation to Subcutaneous Injection of Exenatide (Exendin‐4) in Healthy Subjects

Exenatide is an incretin mimetic with potential glucoregulatory activity in type 2 diabetes. This randomized, single‐blind, placebo‐controlled 6‐way crossover study assessed exenatides effect on acetaminophen pharmacokinetics. Of 40 randomized healthy subjects, 39 completed the study. On the placebo day, acetaminophen (1000 mg) was ingested and placebo injected subcutaneously at 0 hours. On exenatide days, acetaminophen was ingested at −1, 0, +1, +2, and +4 hours, relative to the 10 μg exenatide injected subcutaneously at 0 hours. With exenatide injection, mean plasma acetaminophen AUC0–12 h values were reduced by 11% to 24% (vs placebo). Peak plasma acetaminophen concentrations were similar for the −1‐hour and placebo groups and reduced by 37% to 56% at other times. The most frequent adverse events were generally mild to moderate nausea and vomiting. Exenatide treatment concurrent with or preceding acetaminophen ingestion slowed acetaminophen absorption but had minimal effect on the extent of absorption.

Short-term economic impact of body weight change among patients with type 2 diabetes treated with antidiabetic agents: analysis using claims, laboratory, and medical record data

ABSTRACT Background: Obesity is highly prevalent among patients with type 2 diabetes. Unfortunately, weight gain may also be a consequence of some antidiabetic medications. Although clinical benefits of weight loss have been established, the economic consequence of weight change among patients with type 2 diabetes is unclear. Objectives: The objective was to measure 1‑year total and diabetes-related health care costs associated with weight change during the preceding 6‑month period among type 2 diabetic patients on antidiabetic therapy. Methods: Administrative claims, electronic laboratory data and medical chart information were abstracted for continuously enrolled adults with type 2 diabetes from an health maintenance organization (HMO) for the period from July 1, 1997 through October 31, 2005. To assess the economic impact of weight change, three regression models were applied to estimate the following: (1) the effect of weight change in general (one-slope model); (2) the different effects of weight gain and no weight gain(two-slope model); and (3) the different effects of weight gain and no weight gain (i.e., no change or weight loss) among obese and non-obese patients (four-slope model). Patients included in the study had a baseline weight measurement and a second weight measurement approximately 6 months later. They were also required to be on at least one antidiabetic drug therapy within 1 month around the baseline weight measurement date (index date). Based on the measured weight change, patients were classified into two groups – weight gainers and non-weight gainer. Total health care cost and diabetes-related cost were measured during the 1‑year period following the second weight measurement and were adjusted to 2004 dollars by the medical component of the Consumer Price Index (CPI). Generalized linear models with log link function and gamma distribution were applied to assess the impacts of weight change on the 1‑year total health care cost as well as 1‑year diabetes-related cost. All models controlled for patients’ baseline demographics, comorbidities, body mass index (BMI), glycosylated hemoglobin (HbA1c), and prior resource utilization. Results: The study included 458 patients, of whom 224 (48.9%) experienced minimum weight gain of 1 pound between the two weight measurements. The average 1‑year total health care cost following the second weight measure was

Estimating the Long-Term Cost-Effectiveness of Exenatide in the United States: An Adjunctive Treatment for Type 2 Diabetes Mellitus

6382 and the diabetes-related cost was

Health and economic outcomes for exenatide once weekly, insulin, and pioglitazone therapies in the treatment of type 2 diabetes: a simulation analysis

2002. The mean total health care cost was

Exenatide bid observational study (ExOS): baseline population characteristics of a prospective research study to evaluate the clinical effectiveness of exenatide bid use in patients with type 2 diabetes in a real-world setting

7260 for the weight-gainers and

DB3 REAL-WORLD ANALYSIS OF PERCENT OF PATIENTS WITH TYPE 2 DIABETES ACHIEVING GLYCEMIC GOAL WITH INSULIN GLARGINE

5541 for the non-weight gainers ( p = 0.046), and the mean diabetes-related cost, respectively, was

Metabolic effects of two years of exenatide treatment on diabetes, obesity, and hepatic biomarkers in patients with type 2 diabetes : An interim analysis of data from the open-label, uncontrolled extension of three double-blind, placebo-controlled trials

2141 and

A randomized, open-label, crossover study examiningthe effect of injection site on bioavailability of exenatide (synthetic exendin-4)*

1869 ( p = 0.006). Results from the models showed that one percentage point of weight change was positively associated with a 3.1% (