Emerging utility of once-weekly exenatide in patients with type 2 diabetes.
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SUBMITTER: Goud A
PROVIDER: S-EPMC4621218 | biostudies-literature | 2015
REPOSITORIES: biostudies-literature
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Emerging utility of once-weekly exenatide in patients with type 2 diabetes.
Goud Aditya A Zhong Jixin J Rajagopalan Sanjay S
Diabetes, metabolic syndrome and obesity : targets and therapy 20151021
Type 2 diabetes mellitus (T2DM) is a major risk factor for the development of cardiovascular disease (CVD). Due to the ever increasing incidence of both T2DM and CVD and coexistence of these disorders, numerous agents have been developed over the years to target complications. We focus on the efficacy and safety perspective of a long-acting formulation of the glucagon-like peptide-1 analog exenatide. Our review focuses on the various landmark trials, efficacy, safety profile, and patient perspec ...[more]
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Project description:ObjectiveApproved treatments for type 2 diabetes in pediatric patients include metformin, liraglutide, and insulin. However, approximately one-half of the youth fail metformin monotherapy within 1 year, insulin therapy is associated with challenges, and liraglutide requires daily injections. Consequently, the efficacy and safety of once-weekly injections of exenatide for the treatment of youth with type 2 diabetes was evaluated.Research design and methodsParticipants (aged 10 to <18 years) were randomized (5:2) to once-weekly exenatide 2 mg or placebo, respectively. The primary efficacy end point was change in glycated hemoglobin from baseline to week 24. Secondary efficacy end points were also evaluated, and the frequency of adverse events (AEs) was assessed.ResultsA total of 83 participants were randomized (exenatide, 59; placebo, 24) and 72 completed 24-week treatment (exenatide, 49; placebo, 23). At 24 weeks, the least squares mean change in glycated hemoglobin was -0.36% for the exenatide and +0.49% for the placebo groups (between-group difference, -0.85%; 95% CI -1.51, -0.19; P = 0.012). Nonsignificant least squares mean differences from baseline to 24 weeks favoring exenatide were observed: fasting glucose -21.6 mg/dL (-49.0, 5.7; P = 0.119), systolic blood pressure -2.8 mmHg (-8.0, 2.4; P = 0.284), and body weight -1.22 kg (-3.59, 1.15; P = 0.307). AEs occurred in 36 (61.0%) and 17 (73.9%) participants in the exenatide and placebo groups, respectively.ConclusionsIn youth with type 2 diabetes suboptimally controlled with current treatments, once-weekly exenatide reduced glycated hemoglobin at 24 weeks and was well tolerated.
| S-EPMC9346995 | biostudies-literature
Project description:Aims/introductionTo evaluate the efficacy and safety of once-weekly (q.w.) extended-release exenatide after switching from twice-daily (b.i.d.) exenatide in patients with type 2 diabetes.Materials and methodsThis was an investigator-initiated, prospective, single-arm, multicenter study. Individuals with type 2 diabetes who had been treated with exenatide b.i.d. for at least 3 months were enrolled and switched to exenatide q.w. for 24 weeks. The primary end-point was change in HbA1c at week 24 to test the glucose-lowering effect of exenatide q.w. versus exenatide b.i.d.ResultsA total of 58 Japanese individuals with type 2 diabetes completed the study. Glycated hemoglobin was reduced by 0.2% at week 24 (7.2 ± 1.2% vs 7.0 ± 1.2% [56 ± 13 vs 53 ± 13 mmol/mol], 95% confidence interval -0.4 to -0.03%, P < 0.005 for non-inferiority, P = 0.01 for superiority). Fasting plasma glucose was reduced by 12 mg/dL at week 24 (154 ± 46 vs 142 ± 46 mg/dL, P = 0.02). ?-Cell function assessed by homeostasis model assessment of ?-cell function and C-peptide index was significantly improved at week 24. The incidence of self-reported hypoglycemia was reduced, and treatment satisfaction assessed by the Diabetes Treatment Satisfaction Questionnaire and Diabetes Medication Satisfaction Questionnaire was improved at week 24, with no change in body weight. There was no serious adverse event related to the study drug.ConclusionsSwitching from exenatide b.i.d. to exenatide q.w. resulted in a reduction in glycated hemoglobin, fasting plasma glucose and the incidence of hypoglycemia, and improvement in ?-cell function and treatment satisfaction in patients with type 2 diabetes. These findings will be useful for selecting optimal treatment in individuals with type 2 diabetes.
| S-EPMC7078076 | biostudies-literature
Project description:IntroductionA new formulation of exenatide has become available recently that is the first antidiabetic medication for type 2 diabetes mellitus (T2DM) dosed on a weekly schedule. This review summarizes the pharmacology, efficacy, and safety of exenatide once weekly (exenatide QW). The results are interpreted in terms of the pathophysiology of T2DM, as well as the pharmacology of the new formulation.MethodsRelevant literature on exenatide QW and diabetes was identified through PubMed database searches from inception until September 2013.DiscussionIn the new once-weekly formulation of exenatide, the exenatide molecule is dispersed in microspheres. Following subcutaneous injection, these microspheres degrade in situ and slowly release active agent. In clinical trials, therapy with exenatide QW as monotherapy or in combination with other antidiabetic treatments was associated with reductions in glycated hemoglobin (-1.3% to -1.9%), fasting plasma glucose (-32 to -41 mg/dL), and body weight (-2.0 to -3.7 kg). These outcomes were achieved without an associated increase in the rate of hypoglycemic episodes, except when exenatide QW was used in combination with sulfonylureas. The primary tolerability issues in the trials were gastrointestinal adverse events, particularly during the first weeks of use, although the rate of nausea during startup with exenatide QW was lower than that with the related agents, exenatide twice daily and liraglutide once daily.ConclusionsExenatide QW may be particularly well suited to patients who desire the benefits associated with glucagon-like peptide-1 receptor agonists, including significant glycemic control, low risk of hypoglycemia, and moderate weight loss, but prefer the convenience of once-weekly dosing.
| S-EPMC3961598 | biostudies-literature
Project description:AimsThe Exenatide Study of Cardiovascular Event Lowering (EXSCEL) trial assessed once-weekly exenatide (EQW) vs. placebo, added to usual care in 14,752 patients with type 2 diabetes mellitus (Clinicaltrials.gov: NCT01144338). We assessed the lifetime cost-effectiveness of adding EQW vs. usual care alone from a healthcare perspective.MethodsMedical resource use and EQ-5D utilities were collected throughout the study. Within-trial results were extrapolated to a lifetime horizon using the UK Prospective Diabetes Study Outcomes Model version 2 (UKPDS-OM2), predicting predict cardiovascular and microvascular events. Cost-effectiveness was evaluated separately for US and UK settings, with outcomes measured in quality-adjusted life-years (QALYs).ResultsEQW plus usual care gained 0.162 QALYs at an additional cost of $41,545/patient, compared with usual care in a US setting. The incremental cost-effectiveness ratio (ICER) was $259,223/QALY. In a UK setting, the QALY gain was 0.151 at an additional cost of £6357: an ICER of £42,589/QALY. Sensitivity analyses ranged between $34,369-$269,571 and £3430-£46,560 per QALY gained.ConclusionsIn a lifetime extrapolation, adding EQW to usual care increased QALYs and costs compared with usual care alone. The base-case ICERs exceeded the commonly-cited cost-effectiveness thresholds of $100,000/QALY and £20,000/QALY. However, ICERs were considerably lower in some subgroups, and in sensitivity analyses.
| S-EPMC8844554 | biostudies-literature
Project description:AIMS:To simplify administration of aqueous exenatide once weekly, which requires reconstitution, the exenatide microspheres have been reformulated in a ready-to-use autoinjector with a Miglyol diluent (exenatide QWS-AI). This study compared the efficacy and safety of exenatide QWS-AI with the first-in-class glucagon-like peptide-1 receptor agonist exenatide twice daily (BID). MATERIALS AND METHODS:This randomized, open-label, controlled study in patients with type 2 diabetes using diet and exercise or taking stable oral glucose-lowering medication randomized patients 3:2 to either exenatide QWS-AI (2?mg) or exenatide BID (10??g) for 28?weeks. The primary outcome was the 28-week change in glycated haemoglobin (HbA1c). A subset of patients completed a standardized meal test for postprandial and pharmacokinetic assessments. RESULTS:A total of 375 patients (mean HbA1c, 8.5% [69?mmol/mol]; body mass index, 33.2?kg/m2 ; diabetes duration, 8.5?years) received either exenatide QWS-AI (n?=?229) or exenatide BID (n?=?146); HbA1c was reduced by -1.4% and -1.0%, respectively (least-squares mean difference, -0.37%; P?=?.0072). More patients achieved HbA1c?<7.0% with exenatide QWS-AI (49.3%) than with exenatide BID (43.2%; P?=?.225). Body weight was reduced in both groups (P?=?.37 for difference). Gastrointestinal adverse events (AEs) were reported in 22.7% (exenatide QWS-AI) and 35.6% (exenatide BID) of patients; fewer patients in the exenatide QWS-AI group withdrew because of AEs than in the exenatide BID group. Minor hypoglycaemia occurred most often with concomitant sulfonylurea use. CONCLUSIONS:Exenatide QWS-AI was associated with a greater reduction in HbA1c, similar weight loss and a favorable gastrointestinal AE profile compared with exenatide BID.
| S-EPMC5724491 | biostudies-literature
Project description:BACKGROUND:Exenatide once weekly (QW) is a glucagon-like peptide-1 receptor agonist (GLP-1RA) for the treatment of type 2 diabetes. Safety and tolerability are key considerations in treatment selection. This analysis examines the safety and tolerability profile of exenatide QW, other approved GLP-1RAs (exenatide twice daily and liraglutide once daily), and a pooled population of commonly used non-GLP-1RA treatments. METHODS:Intent-to-treat populations from eight randomized Phase III trials with 24-week and 30-week comparator-controlled periods were analyzed. Data were pooled for exenatide QW, exenatide twice daily, and non-GLP-1RA comparator groups; comparisons between exenatide QW and liraglutide were analyzed separately to better match study groups. The incidence of treatment-emergent adverse events with 95% confidence intervals and exposure-adjusted incidence were calculated. Duration and recurrence were analyzed for gastrointestinal adverse events and adverse events of special interest. RESULTS:Incidences of serious adverse events did not differ between treatments. Discontinuations due to adverse events occurred numerically less frequently with exenatide QW than with other GLP-1RAs but numerically more frequently than with non-GLP-1RA comparators. The most frequent adverse events in the GLP-1RA groups were gastrointestinal and generally mild, with decreasing incidence over time. Gastrointestinal adverse event incidences appeared lower with exenatide QW versus other GLP-1RAs and greater than with non-GLP-1RA comparators. Injection site-related adverse events seemed highest with exenatide QW, but generally did not lead to withdrawal and abated over time. Hypoglycemia was infrequent overall, but occurred numerically more frequently in the non-GLP-1RA comparator group and increased with concomitant sulfonylurea use. Pancreatitis, thyroid cancer, renal failure, and gallbladder disease were rarely reported. CONCLUSION:The overall safety and tolerability profile of exenatide QW was similar to that of other GLP-1RAs, with improved gastrointestinal tolerability. The safety and tolerability profile of exenatide QW compared with non-GLP-1RA comparators was similar overall, with the exception of a lower incidence of hypoglycemia and anticipated differences in gastrointestinal and injection site-related adverse events.
| S-EPMC4445788 | biostudies-literature
Project description:This analysis assessed whether responses with exenatide once weekly plus dapagliflozin (n?=?231), exenatide once weekly alone (n?=?230), or dapagliflozin alone (n?=?233) differed in key patient subpopulations of the DURATION-8 trial. Potential treatment-by-subgroup interactions for changes in glycated haemoglobin (HbA1c) and body weight after 28?weeks were evaluated among subgroups determined by baseline HbA1c, age, sex, body mass index, type 2 diabetes duration, race, ethnicity and estimated glomerular filtration rate (eGFR). Exenatide once weekly plus dapagliflozin reduced HbA1c and body weight across all subgroups: least-squares mean reductions ranged from -8.4 to -26.1?mmol/mol (-0.77% to -2.39%) for HbA1c and from -2.07 to -4.55?kg for body weight. Potential treatment-by-subgroup interactions (P?<?.10) were found for HbA1c change by age (P?= .016) and eGFR (P?= .097). Age subgroup analysis findings were not consistent with expected mechanistic effects, with the small number of patients aged ?65?years (n?=?74 vs n?=?499 for patients aged <65?years) limiting the interpretability of the interaction term. In the exenatide once weekly plus dapagliflozin and dapagliflozin groups, but not the exenatide once weekly group, HbA1c reductions were greater among patients with eGFR ?90 vs ?60 to <90?mL/min/1.73?m2 (least-squares mean reductions of -23.6 vs -19.0?mmol/mol [-2.16% vs -1.74%], -17.3 vs -12.0?mmol/mol [-1.58% vs -1.10%], and -17.7 vs -16.9?mmol/mol [-1.62% vs -1.55%] for the respective treatments); this was consistent with the mechanism of action of dapagliflozin. A potential treatment-by-subgroup interaction was observed for change in body weight by sex (P?= .099), with greater weight loss for women vs men across all treatments (range?-2.56 to -3.98?kg vs -0.56 to -2.99?kg). In conclusion, treatment with exenatide once weekly plus dapagliflozin reduced HbA1c and body weight across all patient subgroups and was more effective than exenatide once weekly or dapagliflozin alone in all adequately sized subgroups.
| S-EPMC5969323 | biostudies-literature
Project description:This post hoc analysis assessed the effects on cardiovascular risk factors of body weight, systolic blood pressure (SBP) and triglycerides after 28?weeks' treatment with exenatide once weekly plus dapagliflozin, as compared with exenatide once weekly or dapagliflozin, in patient subpopulations from the DURATION-8 trial of patients with type 2 diabetes mellitus (T2DM) inadequately controlled with metformin alone. Subgroups of patients were stratified according to their baseline body weight, SBP and triglyceride levels. Body weight, SBP and triglyceride levels were reduced across most respective subgroups, with no significant subgroup-by-treatment interactions. For each treatment, weight loss was numerically greater as baseline body mass index increased. SBP reductions were greater among patients with SBP ?140 vs <140?mm Hg for exenatide once weekly plus dapagliflozin and exenatide once weekly. Reductions in triglyceride levels were greater among patients with baseline triglycerides <1.69 vs ?1.69?mmol/L for each treatment. The combination of exenatide once weekly plus dapagliflozin reduced cardiovascular risk factors across baseline subgroups for each variable to a greater extent than did either individual drug; the greatest effects were observed in the high baseline subgroups for body weight and SBP.
| S-EPMC5969082 | biostudies-literature
Project description:INTRODUCTION:Glucagon-like peptide-1 receptor agonists (GLP-1RAs) improve glycemia in patients with type 2 diabetes, but heart rate increases have been observed. METHODS:A pooled post hoc analysis of 11 randomized clinical trials (N = 4595) of 10-30 weeks' duration from the exenatide once-weekly (QW) development program evaluated heart rate with exenatide QW (intervention group) and exenatide twice daily (BID), liraglutide, and non-GLP-1RAs (insulin, metformin, pioglitazone, and sitagliptin) (comparison groups). The time course and size of heart rate changes from baseline and the relationship of heart rate change with baseline heart rate were studied. A multivariate analysis (9 studies; N = 3903) examined associations between patient characteristics or treatments and heart rate increases. RESULTS:Mean baseline heart rate ± standard deviation was 75.0 ± 8.5 beats per minute (bpm) with exenatide QW (n = 2096), 75.8 ± 8.7 bpm with exenatide BID (n = 606), 75.2 ± 8.9 bpm with liraglutide (n = 450), and 74.5 ± 8.6 bpm with non-GLP-1RAs (n = 1443). Least-squares mean ± standard error changes from baseline to final heart rate were + 2.7 ± 0.2, + 1.0 ± 0.3, and + 3.0 ± 0.4 bpm with exenatide QW, exenatide BID, and liraglutide, respectively, and - 0.8 ± 0.2 bpm with non-GLP-1RAs. The size and direction of heart rate changes in individual patients varied within each treatment group at all time points. At posttreatment follow-up, heart rate reverted to the baseline level after GLP-1RA discontinuation. Heart rate changes correlated negatively with baseline heart rate for all therapies (r = - 0.3 to - 0.4). Baseline heart rate was the strongest predictor of increased heart rate. CONCLUSIONS:Small increases in heart rate were associated with exenatide QW, exenatide BID, and liraglutide treatments but reverted to baseline after discontinuation. Increases were more likely in patients with a low baseline heart rate. The clinical relevance of these heart rate increases is unknown but will be clarified by several ongoing and recently completed cardiovascular outcome studies.
| S-EPMC6104267 | biostudies-literature
Project description:Exenatide once weekly (ExeOW, Bydureon®, Astra Zeneca), a drug belonging to the class of glucagon-like peptide-1 (GLP-1) receptor agonists, is the first agent approved for treatment of type 2 diabetes (T2D) that can be administered on a weekly basis.Data concerning treatment of T2D with ExeOW are reviewed with special reference to its long-term efficacy, tolerability, and safety. Relevant literature was identified through the PubMed database from inception to January 2015.In randomized clinical trials ExeOW, as add-on to oral antidiabetics, achieved significantly improved glycemic control compared to maximum recommended doses of exenatide twice daily, sitagliptin, pioglitazone, and insulin glargine, as measured by HbA1c. In drug-naïve patients ExeOW was superior to sitagliptin and non-inferior to metformin, whereas non-inferiority to pioglitazone and liraglutide was not proven. In different trials reductions in HbA1c ranged from -1.1% to -2.0%. ExeOW therapy over 6 months was also associated with a mean weight loss of -2 to -4 kg, improved systolic blood pressure and lipid profile, and no hypoglycemia unless associated to sulfonylurea. ExeOW long-term therapy up to 3-6 years allowed persistent glycemic control (HbA1c -1.6%), sustained decreases in blood pressure (-2 mmHg), and improvements of lipid profile. ExeOW tolerability was comparable to that of the other GLP-1 receptor agonists, with better gastrointestinal tolerability when direct comparison was done (namely liraglutide and exenatide BID), but higher incidence of injection site reactions and few treatment discontinuations mainly due to gastrointestinal events.ExeOW is a well-tolerated and convenient option for long-term treatment of T2D allowing significant and persistent glycemic control with moderate weight loss and low risk of hypoglycemia unless associated with sulfonylureas.
| S-EPMC5565650 | biostudies-other