[show abstract][hide abstract] ABSTRACT: Objective: Patient numbers in individual diabetes trials are often too limited to assess the effect of a treatment by different patient characteristics, and meta-analyses often do not include patient-level data. The purpose of this pooled analysis was to evaluate the efficacy and tolerability of exenatide once weekly (EQW) in patients with type 2 diabetes grouped into subpopulations by key demographic characteristics. Methods: This post hoc analysis included data from patients who received EQW in seven randomised, controlled phase 3 trials that were 24-30 weeks in duration. Patients were classified into subpopulations on the basis of their baseline age (< 65 or ≥ 65 years), gender (male or female), race (White, Black, Asian, Hispanic), duration of diabetes (< 10 years, ≥ 10 years) and body mass index (BMI; < 25, ≥ 25 to < 30, ≥ 30 to < 35, ≥ 35 to < 40 or ≥ 40 kg/m(2) ). Results: A total of 1719 patients were included in this analysis of patient subpopulations. All subpopulations experienced significant improvements from baseline in haemoglobin A1C, fasting glucose and body weight. Most subpopulations experienced significant improvements in blood pressure and lipid parameters. Overall, the most common AEs were hypoglycaemia (16.4% overall; 2.3% in patients not on concomitant sulfonylurea), nausea (14.7%), diarrhoea (10.9%) and nasopharyngitis (7.2%). Conclusion: These results show that the treatment of type 2 diabetes with EQW for 24-30 weeks was associated with significant improvements in glycaemic control and body weight, irrespective of age, gender, race, duration of diabetes or BMI. The most common adverse events were gastrointestinal in nature.
International Journal of Clinical Practice 08/2012; 66(11):1021-32. · 2.43 Impact Factor
[show abstract][hide abstract] ABSTRACT: Exenatide, a glucagon-like peptide-1 receptor agonist, is used twice daily (BID) as monotherapy or adjunctive therapy for the improvement of glycemic control in patients with type 2 diabetes mellitus. The purpose of this pooled analysis was to evaluate the safety and efficacy of exenatide BID in patients stratified by various demographic characteristics.
This post hoc analysis included data from 16 randomized controlled trials in which patients with type 2 diabetes mellitus were treated with 10-μg exenatide BID. Each patient was classified into subgroups on the basis of his or her baseline values for age (< 65 or ≥ 65 years), sex (male or female), race (white, black, Asian, or Hispanic), duration of diabetes (< 10 years or ≥ 10 years), and body mass index (BMI; ≥ 20 to < 25, ≥ 25 to < 30, ≥ 30 to < 35, or ≥ 35 kg/m(2)).
A total of 2067 patients were included. All groups experienced significant improvements in glycated hemoglobin, fasting plasma glucose levels (other than black patients, who had a relatively low baseline fasting plasma glucose level), and body weight from baseline to endpoint. Most groups had significant improvements in systolic blood pressure. All of the age, sex, and duration of diabetes groups experienced significant improvements in lipid levels (other than high-density lipoprotein cholesterol). Whites and Asians generally experienced significant improvements in lipid levels, whereas blacks and Hispanics did not. Significant improvements in lipid levels were generally seen across BMI groups. The most common adverse events overall were nausea (38.6%), hypoglycemia (28.4%), and vomiting (14.0%). Hypoglycemia was more common overall in patients who were taking a concomitant sulfonylurea than it was in patients who were not.
In this pooled analysis, exenatide BID improved glycemic control and body weight, and had generally beneficial effects on blood pressure and lipid levels in patients regardless of baseline age, sex, race, duration of diabetes, or BMI. Gastrointestinal events were the most common adverse events.Trial registration: www.ClinicalTrials.gov [NCT00039026, NCT00039013, NCT00082381, NCT00035984, NCT00082407, NCT00381342, NCT00360334, NCT00375492, NCT00603239, NCT00765817, NCT00577824, NCT00434954].
Postgraduate Medicine 07/2012; 124(4):21-32. · 1.97 Impact Factor
[show abstract][hide abstract] ABSTRACT: Patients with type 2 diabetes (T2DM) are at risk of long-term vascular complications. In trials, exenatide once weekly (ExQW), a GLP-1R agonist, improved glycemia, weight, blood pressure (BP), and lipids in patients with T2DM. We simulated potential effects of ExQW on vascular complications, survival, and medical costs over 20 years versus standard therapies.
The Archimedes model was used to assess outcomes for ~25,000 virtual patients with T2DM (NHANES 1999-2006 [metformin ± sulfonylureas, age 57 years, body mass index 33 kg/m(2), weight 94 kg, duration T2DM 9 years, hemoglobin A1c [A1C] 8.1%]). The effects of three treatment strategies were modeled and compared to moderate-adherence insulin therapy: advancement to high-adherence insulin at A1C ≥ 8% (treat to target A1C < 7%) and addition of pioglitazone (PIO) or ExQW from simulation start. ExQW effects on A1C, weight, BP, and lipids were modeled from clinical trial data. Costs, inflated to represent 2010 $US, were derived from Medicare data, Drugstore.com, and publications. As ExQW was investigational, we omitted ExQW, PIO, and insulin pharmacy costs.
By year 1, ExQW treatment decreased A1C (~1.5%), weight (~2 kg), and systolic BP (~5 mmHg). PIO and high-adherence insulin decreased A1C by ~1%, increased weight, and did not affect systolic BP. After 20 years, A1C was ~7% with all strategies. ExQW decreased rates of cardiovascular and microvascular complications more than PIO or high-adherence insulin versus moderate-adherence insulin. Over 20 years, ExQW treatment resulted in increased quality-adjusted life-years (QALYs) of ~0.3 years/person and cost savings of $469/life-year versus moderate adherence insulin. For PIO or high-adherence insulin, QALYs were virtually unchanged, and costs/life-year versus moderate-adherence insulin increased by $69 and $87, respectively.
This long-term simulation demonstrated that ExQW treatment may decrease rates of cardiovascular and some microvascular complications of T2DM. Increased QALYs, and decreased costs were also projected.
Vascular Health and Risk Management 01/2012; 8:255-64.
[show abstract][hide abstract] ABSTRACT: The Exenatide BID Observational Study (ExOS) was designed to evaluate the clinical effectiveness of exenatide BID use in patients with type 2 diabetes (T2D) in a real-world clinical practice setting in the United States.
Patients were enrolled from 74 practice sites from 9/2007 through 1/2009 and followed for 12 months. The primary effectiveness endpoint was achieving or maintaining hemoglobin A1C of ≤7.0%, or an absolute drop of 0.5% from baseline. Secondary measures included absolute and percentage change from baseline for a variety of clinical measures (lipid markers, weight, BMI, etc.), and quality of life (QOL) was assessed using the Impact of Weight on Quality of Life (IWQOL)-Lite.
A total of 452 patients were included in the primary study population. At baseline, patients (60% female) had mean (SD) age of 55 (11), T2D duration of 9 (8) years, HbA1c of 8.0 (1.7) %, and body mass index (BMI) of 38.2 (7.4) kg/m(2). Family history of T2D was reported in 73.9% of patients. Hypertension was reported in 61.5% of patients, and 47.1% had hyperlipidemia. The HbA1c goal was achieved in 76.3% of the 118 patients with A1C measurements available at 12 months (P < 0.0001). Patients with available clinical measurements achieved significant improvements in HbA1c, weight, BMI, and QOL measurements at 12 months. A mean improvement of 4.56 was seen in the total IWQOL-Lite score at 12 months (P = 0.001). The single-arm design of this study is a limitation; however, the overall objective of the study was to observe patients on exenatide BID therapy over time, comparing their status at endpoint to baseline, rather than to make comparisons among different drug therapies.
The Exenatide BID Observational Study supports the clinical effectiveness of exenatide BID observed in previous clinical trials and retrospective database studies.
Current Medical Research and Opinion 11/2011; 27(12):2335-42. · 2.26 Impact Factor
[show abstract][hide abstract] ABSTRACT: The objective of this study was to examine the frequency of hypoglycemia among patients with type 2 diabetes who had concomitantly used exenatide BID (exenatide) and long-acting insulin and continued this combination vs those who continued long-acting insulin alone.
Retrospective analyses, using a large managed care database, were used to estimate the frequency of hypoglycemia (episodes/patient/6 months) for patients who concomitantly used exenatide and long-acting insulin during a 6-month follow-up period.
From among 2082 patients on concomitant exenatide and long-acting insulin, those who continued this combination (n=472) had a lower frequency of hypoglycemia compared to those who remained on long-acting insulin alone (n=312) (0.03 ± 1.9 vs 0.10 ± 1.01 [episodes/patient/6 months]; p<0.0001).
Only hypoglycemia that required medical intervention (coded for hypoglycemia) was captured. The study could not evaluate any association between insulin dose titration and hypoglycemia or examine other outcomes such as HbA1c, weight, and body mass index, due to lack of data availability.
Patients who concomitantly used exenatide BID and long-acting insulin experienced a lower rate of hypoglycemia.
Journal of Medical Economics 09/2011; 14(6):705-8.
[show abstract][hide abstract] ABSTRACT: To describe the Exenatide Observational Study (ExOS) and patients initiating exenatide therapy in a real-world clinical practice setting.
ExOS is a prospective, single-arm, multicenter, observational study to assess the effectiveness of up to 24 months of exenatide therapy in patients with type 2 diabetes (T2D). Patients with T2D ≥18 years of age, who initiated exenatide therapy, were eligible. The primary effectiveness endpoint is achieving or maintaining hemoglobin A1C of ≤7.0%, or an absolute drop of 0.5% from baseline. Secondary objective measures evaluate the absolute and percentage changes from baseline for a variety of clinical measures (lipid markers, weight, BMI, etc.) and quality of life (QOL) is assessed using the Impact of Weight on Quality of Life (IWQOL)-Lite.
On average, the baseline population (n = 531) was aged 55 years, predominantly female (62%), white (79%), educated, obese (mean BMI 39 kg/m(2)), with mean HbA(1c), blood pressure, total cholesterol, and triglyceride values of 8.0%, 129/76 mmHg, 174 mg/dL, and 197 mg/dL, respectively. A total of 28% entered the study with HbA(1c) ≤7.0% and 67% were being treated with oral antihyperglycemic drug(s) (OAD) only [1 (28.4%), 2 (28.4%), >2 (10.2%)], or some form of insulin ±OADs (19%), and ≥50% were on a cholesterol-lowering drug(s) ± antihypertensive medication(s). The single-arm design of this study is a limitation; however, the overall objective of the ongoing study is to observe patients on exenatide therapy over time, comparing their status at endpoint to baseline, rather than to make comparisons among different drug therapies.
Patients treated with exenatide tended to be obese, middle-aged women on various combinations of OADs and/or insulin who often had hypertension and/or dyslipidemia. Further planned analyses will provide the largest sample of prospective data on outcomes of exenatide therapy for up to 24 months in this usual-care population.
Current Medical Research and Opinion 03/2011; 27(3):531-40. · 2.26 Impact Factor