Determining Predictors of Early Response to Exenatide in Patients with Type 2 Diabetes Mellitus (original) (raw)
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Diabetes & Metabolism, 2010
The study objective was to analyze, in everyday practice, the long-term metabolic effects of exenatide (for 9 and 12 months) in patients with type 2 diabetes not responding to treatments with metformin and sulphonylurea at maximum dosages. A total of 299 type 2 diabetics were recruited from 14 centres specializing in diabetes care across Belgium. Main study endpoints were changes in HbA(1c), weight and waist circumference, and tolerability and compliance. Two patient cohorts were analyzed for effectiveness, with data available at 9 (n=90) and 12 (n=94) months of follow-up. Significant decreases in HbA(1c) of -1.3% and -1.6% were observed in the 9- and 12-month cohorts, respectively (P<0.001). The decrease in HbA(1c) was greater in patients with higher baseline levels (P<0.001), and the response was independent of baseline weight, body mass index (BMI), age, gender and diabetes duration. A progressive reduction of weight (4.9 kg) was also observed in the two cohorts at 9 and 12 months (P<0.001), with greater weight loss in patients with higher baseline BMI (P=0.046) and in female subjects (P=0.025). Waist circumference also decreased from baseline to endpoints. A correlation was observed between reduction in HbA(1c) and weight loss (P=0.019). Side effects, mainly of gastrointestinal origin, were reported in 33% (93/284 patients in the safety cohort). The rate of hypoglycaemia was 3.5%. Treatment was discontinued in 27% of patients (n=77) mainly due to drug inefficacy (53%, n=41) or adverse events (26%, n=20), or both (8%, n=6). Exenatide leads to long-term improvement of glycaemic control as well as weight loss in a majority of patients not responding to combined oral drug therapy in real-world clinical practice. However, no baseline factors predictive of response could be identified. Exenatide can be considered an effective treatment option in such patients, including those with high baseline HbA(1c) and long duration of diabetes.
Current Medical Research and Opinion, 2011
Background V-Go is a wearable, patch-like, 24-h insulin delivery device that delivers both a continuous preset basal rate and on-demand bolus dosing. The aim of this study was to observe glycemic control, insulin dosing, and hypoglycemia risk in patients switched to V-Go in a real-world setting. The primary objective was to compare change in mean hemoglobin A1c (HbA1c) from baseline to the end of V-Go use. Methods This prospective, open-label, multicenter study recruited patients with type 2 diabetes (T2D) and suboptimal glycemic control (HbA1c ≥ 7%) across 28 centers. Efficacy analyses were conducted for all patients with a post-baseline HbA1c and results stratified based on prior antihyperglycemic medication therapies. Insulin dosing was at the discretion of the health care provider and the protocol did not mandate glycemic targets. Treatment satisfaction surveys were utilized to gain patient feedback on the use of V-Go. Results One hundred eighty-eight patients were enrolled in the study, among whom 140 patients had a valid post-baseline HbA1c and were included in the primary efficacy analysis. Use of V-Go resulted in a change of − 0.64%; (P = 0.003) in HbA1c from baseline, and in those prescribed insulin, the total daily dose of insulin was decreased by 12 units/day (P < 0.0001). Twenty-two patients (12%) reported hypoglycemic events (≤ 70 mg/dL), with an event rate of 1.51 events/ patient/year. Conclusion In a T2D population with suboptimal HbA1c, initiating V-Go therapy in a real-world setting significantly improved glycemic control and led to significant insulin dose reductions. ClinicalTrial.gov registry identifier: NCT01326598.
Diabetes, Obesity and Metabolism, 2009
This study evaluated changes in clinical effectiveness measures of patients with type 2 diabetes initiating exenatide therapy in a real-world setting. Eligible patients identified in the General Electric (GE) electronic medical record (EMR) research database from 1 January 2000 through 31 December 2007 were > or =18 years old with type 2 diabetes. Patients had prescription orders in the previous 395 days for metformin, a sulfonylurea, or a thiazolidinedione as monotherapy or in combination, and had at least 6 months of follow-up activity. Baseline clinical measures were documented from 45 days prior up to 15 days after exenatide initiation and follow-up measures documented at 6 months +/- 45 days. A total of 1709 patients were identified for study inclusion. The overall mean A1C reduction (s.e.m.) at 6 months was -0.8% (0.05) (p<0.001), weight loss was -3.2 kg (0.14) (p<0.001), blood pressure (BP) lowering was -1.9 mmHg (0.46) systolic blood pressure (SBP) (p<0.001) and -0.5 mmHg (0.27) diastolic blood pressure (DBP) (p = 0.078). Changes in low-density lipoprotein (LDL), triglycerides and HDL were -7.4 mg/dl (1.7) (p<0.001), -23.2 mg/dl (6.7) (p = 0.001) and -0.8 mg/dl (0.33) (p = 0.012) respectively. In a quartile analysis by weight loss, mean A1C reduction ranged from -1.1 to -0.65% in the highest to lowest weight loss quartiles respectively. In a real-world setting, exenatide initiation is associated with significant improvements in the measures of clinical effectiveness for type 2 diabetes. These reductions were comparable to those reported in randomized, controlled registration trials after 6 months of therapy.
A review of exenatide as adjunctive therapy in patients with type 2 diabetes
Drug Design, Development and Therapy, 2009
Background: Incretin glucagon-like peptide-1 (GLP-1) is a hormone released from cells in the gastrointestinal tract (GI), leading to glucose-dependent insulin release from the pancreas. It also suppresses postprandial hyperglycemia, glucagon secretion and slows gastric emptying. Exenatide (EXE), a functional analog of human GLP-1, was approved by the US FDA in April 2005. Objective: This article reviews current primary literature on the clinical efficacy and safety of EXE in the treatment of type 2 diabetes mellitus (DM) and describes the pharmacokinetics, pharmacodynamics, dosing and administration of EXE. Methods: English-language articles were identified through a search of MEDLINE (1966 to March 2009), International Pharmaceutical Abstracts (1970, and Cochrane Database of Systemic Reviews (1995 to March 2009). Search terms included EXE, diabetes mellitus, postprandial hyperglycemia, gastric emptying, glucagon, pharmacokinetics and pharmacodynamics. Articles were selected for review if their designs were randomized, blinded and of controlled design that focused on clinical outcomes of patients with type 2 DM. Results: EXE is administered subcutaneously in the thigh, abdomen or upper arm within the 60-minute period before the morning and evening meals. Its C max is reached within 2.1 hours, and its T 1/2 in 2.4 hours. EXE's metabolism is primarily through the kidneys. For the patients who received EXE 10 µg SC BID in three, 30-week, placebo-controlled studies with background sulfonylureas (SUs), metformin (MET), or SU + MET, there were significant reductions in HbA 1c (0.77 to 0.86%), fasting plasma glucose (0.6 mmol/L) and body weight (1.6 to 2.8 kg) (P 0.05 vs PCB) that were sustained in patients who completed two open-label phase trials with an additional 52 weeks of therapy. The use of thiazolidinediones was associated with a slight advantage over EXE in improving HbA 1c along with increased weight gain; those who received EXE lost weight, but experienced more GI adverse effects. Patients who received EXE lost significant body weight while patients who received insulin gained weight. Patients receiving insulin had lower fasting, prelunch and predinner glucose excursions while patients in the EXE groups had lower postprandial glucose levels. Nausea was most frequently (>20%) reported in patients receiving the highest dose of EXE (10 µg SC BID vs 5 µg SC BID). Conclusions: EXE at the dose of 10 µg SC BID has been proven to decrease HbA lc by 1.3% ± 0.1% and decrease body weight by up to 5.3 ± 0.8 kg at week 82. Nausea was the most frequently reported adverse event (.20%) especially in patients being treated with EXE 10 µg SC BID. EXE can be safely added to MET therapy, SU therapy or MET + SU combination to effectively target glycemic goals in patients with type 2 DM. Long-term, head-to-head studies assessing the effect of the EXE ± oral agents/insulins in patients with HbA lc 10% are still needed to fully clarify the role of EXE in poorly controlled patients with type 2 DM.
Health and quality of life outcomes, 2006
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. Patients were randomized to either twice daily exenatide or once daily insulin glargine during a 26-week international trial. At baseline and endpoint, five patient-reported outcome measures were administered: the Vitality Scale of the SF-36, The Diabetes Symptom Checklist - Revised (DSC-R), the EuroQol EQ-5D, the Treatment Flexibility Scale (TFS), an...
Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy, 2013
Purpose: To investigate whether gender affects therapeutic response by exenatide twice a day (BID) in type 2 diabetes by using a database concerning patients monitored by five outpatient clinics in Tuscany, Italy. Patients and methods: We considered a cohort of 315 (154 male/161 female) patients experiencing therapeutic failure while on oral therapy (metformin, or combination therapy metformin + sulphonylureas), who were given exenatide (10 µg/BID) and who fully completed 4 months, 8 months, and 12 months of follow-ups. Results: Among patients stratified by gender and well matched for age, body mass index, and hemoglobin A 1c (HbA 1c ), it was found that the length of disease was longer in females than in males (12 ± 8 years versus 10 ± 7 years; P = 0.037), and the ratio of patients on metformin to those on combination therapy was higher in men (P = 0.018). Target glycemic response (1-year HbA 1c # 7%) was achieved in a significantly higher proportion of males than females (38% versus 27%; χ 2 = 4.66; P = 0.03). Target weight loss expressed as 1-year weight percent fall from baseline $ 75th percentile (8.5%) was significantly higher in females at 8 and 12 months (P , 0.05; for both). One-year glycemic target response was inversely related to baseline HbA 1c levels and diabetes duration among males, while metformin therapy (compared to oral combination therapy) was a significant predictor of better glycemic targets among females. Homeostasis model assessment-B, measured in 117 patients, predicted hypoglycemic response only in women (P = 0.009). Target 1-year weight loss was predicted by longer diabetes duration among males and by lower baseline HbA 1c among females. Finally, no significant difference between genders was noted as to gastrointestinal side effects after exenatide therapy. Conclusion: According to this "real world" experience, predictors of glycemic control and body weight loss after 12 months of exenatide BID therapy are different between genders in type 2 diabetes.
Clinical Therapeutics, 2016
Purpose: Data comparing real-world effectiveness of the glucagon-like peptide-1 receptor agonists (GLP-1RAs) exenatide once weekly (QW) and liraglutide in the treatment of type 2 diabetes (T2D) are limited. Furthermore, there is limited information on exenatide QW or liraglutide response by glycemic control and insulin use status. This study identifies 1-year glycosylated hemoglobin (HbA 1c) and weight outcomes with exenatide QW and liraglutide in the real-world setting overall and in insulin-naive patients with uncontrolled T2D. Methods: This retrospective cohort study using national electronic medical record data compared 1-year HbA 1c and weight outcomes in patients with T2D prescribed exenatide QW or liraglutide. Included patients were adults (Z18 years old) with T2D who were GLP-1RA naive when newly prescribed exenatide QW or liraglutide between January 1, 2012, and March 31, 2013 (index date). Outcomes were reported descriptively overall and in subsets of insulinnaive patients with baseline HbA 1c Z7.0% or Z9.0%. Multivariable linear regression analyses were performed to estimate adjusted change in HbA 1c and weight. Findings: The study included 808 exenatide QW and 4333 liraglutide patients. Mean (SD) age was 57 (11) years in both groups. Mean baseline HbA 1c was 8.3% (1.5%) in exenatide QW patients and 8.4% (1.6%) in liraglutide patients (P ¼ 0.66); 16 (2%) of the exenatide QW and 1099 (25.4%) of the liraglutide patients were newly prescribed insulin on the index date (P o 0.001). Adjusted mean HbA 1c change at 1 year was À0.37% (95% CI, À0.53% to À0.21%) for exenatide QW and À0.37% (95% CI, À0.55% to À0.18%) for liraglutide. Adjusted HbA 1c reduction was more pronounced in insulin-naive patients with baseline HbA 1c Z7.0% (À0.71% and À0.80% for the exenatide QW and liraglutide patients, respectively, P 4 0.05) and Z9.0% (À1.73% and À1.57% for exenatide QW and liraglutide patients, respectively, P 4 0.05). Mean (adjusted) weight loss was À2.22 kg (95% CI, À3.06 to À1.37 kg) with exenatide QW and À2.21 kg (95% CI, À3.18 to À1.23 kg) with liraglutide. Implications: Exenatide QW and liraglutide lead to similar HbA 1c and weight reductions at 1 year in the real-world setting. Greater HbA 1c reductions occurred in insulin-naive patients with baseline HbA 1c Z7.0%. Both agents are appropriate options for patients needing antidiabetes therapy to lower HbA 1c while promoting weight loss.