Safety and Efficacy of Exenatide Once Weekly in Participants with Type 2 Diabetes and Stage 2/3 Chronic Kidney Disease.
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SUBMITTER: Guja C
PROVIDER: S-EPMC7324446 | biostudies-literature | 2020 Jul
REPOSITORIES: biostudies-literature
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Safety and Efficacy of Exenatide Once Weekly in Participants with Type 2 Diabetes and Stage 2/3 Chronic Kidney Disease.
Guja Cristian C Frías Juan P JP Suchower Lisa L Hardy Elise E Marr Galina G Sjöström C David CD Jabbour Serge A SA
Diabetes therapy : research, treatment and education of diabetes and related disorders 20200418 7
<h4>Introduction</h4>The safety and efficacy of exenatide once weekly (EQW) is overall well established. EQW is primarily renally eliminated. In this study, the efficacy and renal and gastrointestinal tolerability of EQW were summarised in participants with type 2 diabetes and chronic kidney disease stage 3 (CKD3; moderate renal impairment; estimated glomerular filtration rate [eGFR] ≥ 30 to < 60 mL/min/1.73 m<sup>2</sup>) or CKD stage 2 (CKD2; mild renal impairment; eGFR ≥ 60 to < 90 mL/min/1.7 ...[more]
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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: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
Project description:We recently reported that after 26 weeks, exenatide once weekly (EQW) resulted in superior A1C reduction, reduced hypoglycemia, and progressive weight loss compared with daily insulin glargine (IG) in patients with type 2 diabetes who were taking metformin alone or with sulfonylurea. This 84-week extension study assessed the long-term safety and efficacy of EQW versus IG.This multicenter, open-label, randomized, two-arm, parallel trial assessed change in A1C, proportions of patients achieving A1C <7.0 and ?6.5%, body weight, incidence of hypoglycemia, and overall safety.Of 415 patients who completed 26 weeks, 390 (194 EQW and 196 IG patients) entered the extension study. At 84 weeks, A1C decreased from baseline (8.3%) by -1.2% for EQW vs. -1.0% for IG (P = 0.029). The proportions of patients who achieved end point A1C targets <7.0 and ?6.5% were 44.6% for EQW patients vs. 36.8% for IG patients (P = 0.084) and 31.3% for EQW patients vs. 20.2% for IG patients (P = 0.009), respectively. Patients taking EQW lost 2.1 kg of body weight, whereas those taking IG gained 2.4 kg (P < 0.001). Among patients taking metformin plus sulfonylurea, the incidence of minor hypoglycemia was 24% for EQW patients vs. 54% for IG patients (P < 0.001); among patients taking metformin alone, it was 8% for EQW patients vs. 32% for IG patients (P < 0.001). Among adverse events occurring in ?5% of patients, diarrhea and nausea occurred more frequently (P < 0.05) in the EQW group than in the IG group (12 vs. 6% and 15 vs. 1%, respectively).After 84 weeks, patients treated with EQW continued to experience better glycemic control with sustained overall weight loss and a lower risk of hypoglycemia than patients treated with IG.
| S-EPMC3308312 | 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: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 perspectives of weekly exenatide that delineates its current and future role in the treatment of patients with T2DM and CVD.
| S-EPMC4621218 | biostudies-literature
Project description:OBJECTIVE:Among patients with type 2 diabetes uncontrolled with metformin, exenatide once weekly (QW) plus dapagliflozin combination produced greater reductions in glycemia, weight, and systolic blood pressure (SBP) at 28 weeks than exenatide QW or dapagliflozin alone (DURATION-8). Here, we investigated the safety and maintenance of efficacy at 52 weeks, after a 24-week extension. RESEARCH DESIGN AND METHODS:This phase 3, multicenter, double-blind study randomized adults with type 2 diabetes (with glycated hemoglobin [HbA1c] 8.0-12.0% [64-108 mmol/mol] and on metformin ≥1,500 mg/day) to exenatide QW (2-mg subcutaneous injection) plus once-daily dapagliflozin (10-mg oral tablet), exenatide QW plus oral placebo, or dapagliflozin plus injected placebo. Extension-period P values were nominal. RESULTS:Of 1,375 patients screened, 695 were randomized (mean baseline HbA1c 9.3% [78 mmol/mol]); 81.2% completed the study, and 75.3% completed treatment. At 52 weeks, HbA1c reductions were greater with exenatide QW plus dapagliflozin (least squares mean change -1.75% [-19.1 mmol/mol]) versus exenatide QW (-1.38% [-15.1 mmol/mol]; P = 0.006) or dapagliflozin (-1.23% [-13.4 mmol/mol]; P < 0.001); mean HbA1c values were 6.9% (52 mmol/mol), 7.2% (55 mmol/mol), and 7.4% (57 mmol/mol), respectively. Weight and SBP reductions were greater with exenatide QW plus dapagliflozin (-3.31 kg and -4.5 mmHg) versus exenatide QW (-1.51 kg and -0.7 mmHg; both P < 0.001) but similar to those with dapagliflozin (-2.28 kg and -2.7 mmHg; P = 0.057 and P = 0.100, respectively). The exenatide QW plus dapagliflozin regimen was well tolerated with no unexpected safety findings; more patients treated with exenatide QW experienced gastrointestinal and injection site-related adverse events. No major hypoglycemia occurred. CONCLUSIONS:Among patients with type 2 diabetes uncontrolled with metformin, exenatide QW plus dapagliflozin provided sustained improvements in glycemia, weight, and SBP over 52 weeks, with no unexpected safety findings.
| S-EPMC6150435 | biostudies-other
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:AimsGlucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors treat type 2 diabetes through incretin-signaling pathways. This study compared the efficacy and safety of the glucagon-like peptide-1 receptor agonist exenatide once-weekly (Miglyol) suspension for autoinjection (QWS-AI) with the dipeptidyl peptidase-4 inhibitor sitagliptin or placebo.Materials and methodsIn this open-label, multicentre study of patients with type 2 diabetes who had suboptimal glycaemic control on metformin monotherapy, 365 patients were randomized to receive exenatide 2.0?mg QWS-AI, sitagliptin 100?mg once daily or oral placebo (3:2:1 ratio). The primary endpoint was change in glycated hemoglobin (HbA1c) from baseline to 28?weeks.ResultsAt 28?weeks, exenatide QWS-AI significantly reduced HbA1c from baseline compared to sitagliptin (-1.13% vs -0.75% [baseline values, 8.42% and 8.50%, respectively]; P ?=?.02) and placebo (-0.40% [baseline value, 8.50%]; P?=?.001). More exenatide QWS-AI-treated patients achieved HbA1c <7.0% than did sitagliptin- or placebo-treated patients (43.1% vs 32.0% and 24.6%; both P ?<?.05). Exenatide QWS-AI and sitagliptin reduced fasting plasma glucose from baseline to 28?weeks (-21.3 and -11.3?mg/dL) vs placebo (+9.6?mg/dL), with no significant difference between the 2 active treatments. Body weight decreased with both active treatments (-1.12 and -1.19?kg), but not with placebo (+0.15?kg). No improvement in blood pressure was observed in any group. The most common adverse events with exenatide QWS-AI were gastrointestinal events and injection-site reactions.ConclusionsThis study demonstrated that exenatide QWS-AI reduced HbA1c more than sitagliptin or placebo and was well tolerated.
| S-EPMC5485171 | 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:AIM:To assess the effects of once-weekly exenatide on 24-hour glucose control and variability. MATERIALS AND METHODS:This double-blind, placebo-controlled trial randomized metformin-treated adults with type 2 diabetes to once-weekly exenatide 2.0 mg or placebo. Continuous glucose monitoring (CGM) was performed at baseline and weeks 4 and 10. The primary outcome was change in CGM-measured 24-hour mean glucose level. RESULTS:In the once-weekly exenatide (n = 60) and placebo (n = 56) groups (modified intention-to-treat population), the baseline glycated haemoglobin (HbA1c) concentrations were 8.2% and 8.0%, respectively, and the fasting plasma glucose (FPG) concentration was 9.86 and 9.32 mmol/L, respectively. Once-weekly exenatide significantly (p < 0.001) reduced 24-hour mean glucose level versus placebo (week 4, -1.44 vs -0.29 mmol/L; week 10, -1.71 vs -0.17 mmol/L), with consistent control throughout the week. Once-weekly exenatide significantly reduced FPG and 2-hour postprandial glucose (PPG) levels versus placebo at week 4 (FPG, -1.65 vs -0.11 mmol/L; PPG, -1.79 vs -0.11 mmol/L) and week 10 (FPG, -2.32 vs -0.28 mmol/L; PPG, -2.46 vs -0.33 mmol/L). At week 10, once-weekly exenatide reduced the mean amplitude of glucose excursions (MAGE; -0.84 vs 0.16 mmol/L) and standard deviation (s.d.) of mean glucose (-0.35 vs 0.04 mmol/L). By week 10, once-weekly exenatide-treated participants spent more time in euglycaemia (once-weekly exenatide, 77% vs placebo, 58%), less time in hyperglycaemia (22% vs 42%), and a similar time in hypoglycaemia (0.7% vs 0.3%). Common adverse events were injection-site nodule (once-weekly exenatide, 10.0% vs placebo, 0.0%), urinary tract infection (6.7% vs 8.9%) and nausea (6.7% vs 0.0%). CONCLUSIONS:In metformin-treated participants with type 2 diabetes, once-weekly exenatide significantly improved daily glucose control and reduced glycaemic variability at weeks 4 and 10, as shown by reductions in 24-hour glucose, FPG and PPG levels, MAGE and s.d., and increased time spent in euglycaemia.
| S-EPMC6168745 | biostudies-literature