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Aims: Exenatide is a glucagon-like peptide-1 receptor agonist shown to improve glycaemic control in patients with type 2 diabetes (T2DM).Intermittent exenatide exposure is achieved with the twice-daily formulation (ExBID), while t...
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Aims: Exenatide is a glucagon-like peptide-1 receptor agonist shown to improve glycaemic control in patients with type 2 diabetes (T2DM).Intermittent exenatide exposure is achieved with the twice-daily formulation (ExBID), while the once-weekly formulation (ExQW) providescontinuous exenatide exposure. This integrated, retrospective analysis compared safety and tolerability of ExQW vs. ExBID in patients withT2DAA.Methods: Data were pooled from two open-label, randomized, comparator-controlled, trials directly comparing ExQW (N = 277) to ExBID(N = 268). Between-group differences in adverse event (AE) and hypoglycaemia incidences were calculated. Incidence over time and durationof selected AEs (nausea, vomiting, and injection-site-related AEs) were also summarized.Results: The most common AEs were nausea, diarrhoea, injection-site pruritus, and vomiting. Nausea and vomiting occurred less frequentlywith ExQW vs. ExBID, peaking at initiation (ExQW) or at initiation and dose escalation (ExBID), and decreasing over time. Few patientsdiscontinued because of gastrointestinal-related AEs. Injection-site AEs were more common with ExQW but decreased over time in both groups.No major hypoglycaemia occurred; minor hypoglycaemia occurred with low incidence in patients not using concomitant sulphonylurea, with nodifference between ExQW and ExBID. Serious AEs and discontinuations because of AEs were reported with similar frequency in both groups.Conclusions: Both exenatide formulations were generally safe and well-tolerated, with ExQW associated with less nausea and vomiting butmore injection-site AEs. Continuous vs. intermittent exposure did not impact the overall tolerability profile of exenatide, with no evidence ofprolonged duration or worsened intensities of AEs with continuous exposure.
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These preclinical studies aimed to 1) increase our understanding the dietary induction of nonalcoholic steatohepatitis (NASH), and, 2) further explore the utility and mechanisms of glucagon-like peptide-1 receptor (GLP-1R) agonism...
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These preclinical studies aimed to 1) increase our understanding the dietary induction of nonalcoholic steatohepatitis (NASH), and, 2) further explore the utility and mechanisms of glucagon-like peptide-1 receptor (GLP-1R) agonism in NASH. We compared the effects of a high trans-fat (HTF) or high lard fat (HLF) diet on key facets of nonalcoholic fatty liver disease (NAFLD)/NASH in Lep ob/Lep ob and C57BL6J (B6) mice. Although HLF-fed mice experienced overall greater gains in weight and adiposity, the addition of trans-fat better mirrored pathophysiological features of NASH (e.g., hepatomegaly, hepatic lipid, and fibrosis). Administration of AC3174, an exenatide analog, and GLP-1R agonist to Lep ob/Lep ob and B6 ameliorated hepatic endpoints in both dietary models. Next, we assessed whether AC3174-mediated improvements in diet-induced NASH were solely due to weight loss in HTF-fed mice. AC3174-treatment significantly reduced body weight (8.3%), liver mass (14.2%), liver lipid (12.9%), plasma alanine aminotransferase, and triglycerides, whereas a calorie-restricted, weight-matched group demonstrated only modest nonsignificant reductions in liver mass (9%) and liver lipid (5.1%) relative to controls. Treatment of GLP-1R-deficient (GLP-1RKO) mice with AC3174 had no effect on body weight, adiposity, liver or plasma indices pointing to the GLP-1R-dependence of AC3174's effects. Interestingly, the role of endogenous GLP-1Rs in NASH merits further exploration as the GLP-1RKO model was protected from the deleterious hepatic effects of HTF. Our pharmacological data further support the clinical evaluation of the utility of GLP-1R agonists for treatment of NASH. ? 2012 the American Physiological Society.
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Exenatide, a glucagon-like peptide-1 (GLP-1) receptor agonist, is effective in inducing weight loss. The exact mechanisms are not fully understood. Reduced appetite and food intake may play important roles. Sweet taste contributes...
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Exenatide, a glucagon-like peptide-1 (GLP-1) receptor agonist, is effective in inducing weight loss. The exact mechanisms are not fully understood. Reduced appetite and food intake may play important roles. Sweet taste contributes to food palatability, which promotes appetite. Interestingly, GLP-1 and its receptor are expressed in the taste buds of rodents and their interaction has an effect on mediating sweet taste sensitivity. Our aim was to investigate whether sweet taste will be changed after long term treatment with exenatide. The results showed that high-fat diet induced obese rats (HF-C) presented metabolic disorders in food intake, body weight, blood glucose and lipid metabolism compared with long term exenatide treated obese rats (EX) and normal chow fed control rats (NC). Meanwhile, greater preference for sweet taste was observed in HF-C rats but not in EX rats. Compared with NC rats, brain activities induced by sweet taste stimulation were stronger in HF-C rats, however these stronger activities were not found in EX rats. We further found reduced sweet taste receptor T1R3 in circumvallte taste buds of HF-C rats, while GLP-1 was increased. Besides, serum leptin was evaluated in HF-C rats with decreased leptin receptor expressed in taste buds. These changes were not observed in EX rats, which suggest them to be the underlying hormone and molecular mechanisms responsible for alterations in sweet taste of HF-C rats and EX rats. In summary, our results suggest that long term treatment with exenatide could benefit dietary obese rats partially by reversing sweet taste changes.
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We investigate the effects of exenatide on excessive daytime sleepiness (EDS), driving performance and depression score in patients with type 2 diabetes with EDS. Eight obese patients with diabetes but without obstructive sleep ap...
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We investigate the effects of exenatide on excessive daytime sleepiness (EDS), driving performance and depression score in patients with type 2 diabetes with EDS. Eight obese patients with diabetes but without obstructive sleep apnoea (OSA) participated in a placebo-controlled single-blind study during which multiple wakefulness and sleep latency test, Epworth score, driving performance, depression score, fasting glucose and glycated haemoglobin (HbA1c) levels were assessed at baseline, end of placebo and treatment phase at baseline and after 22weeks of treatment. Mean (±standard error of the mean) age, body mass index (kgm2) and HbA1c [mmolmol-1 (%)] of patients at baseline were 50±4.9years, 37.6±1.1 and 65±19 (8.06±0.41), respectively. When compared to placebo, exenatide treatment was associated with a decrease in both subjective and objective sleepiness, based on the Epworth score reduction and the sleep latency increase assessed by multiple objective sleepiness and sustained attention (OSLER) tests, respectively. Mean sleep latency time (adjusted for change in HbA1c and weight) were 32.1±1.7, 29.1±1.7 and 37.7±1.7, respectively (P=0.002). Modelling for covariates suggested that improvement in mean sleep latency time is predicted by changes in weight (P=0.003), but not by changes in HbA1c (P=0.054). Epworth sleepiness score was reduced significantly (values for placebo versus exenatide: 11.3±1.2 versus 5.7±1.3; P=0.003). No significant change was noted in the depression score and driving performance. Exenatide is associated with a significant reduction in objective sleepiness in obese patients with type 2 diabetes without OSA, independent of HbA1c levels. These findings could form a basis for further studies to investigate the pathophysiological mechanisms of sleepiness in obese patients with type 2 diabetes.
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Exenatide is a relatively new drug for the treatment of type 2 diabetes. There have been four previous cases of ischaemic renal failure reported with exenatide. We report two cases of renal failure associated with exenatide.
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A 58-year-old Caucasian man with type 2 diabetes diagnosed in 1996 was started on exenatide (Byetta). His weight was 117kg and he had a body mass index (BMI) of 39kg/m~2. He was taking 126 units of insulin per day with metformin. ...
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A 58-year-old Caucasian man with type 2 diabetes diagnosed in 1996 was started on exenatide (Byetta). His weight was 117kg and he had a body mass index (BMI) of 39kg/m~2. He was taking 126 units of insulin per day with metformin. Previous attempts at weight loss had been unsuccessful. Over a period of six months, he lost 20kg in weight (BMI 30kg/m~2). He reported nausea and vomiting, attributed to the exenatide, but because he was pleased with the weight loss he wanted to continue on exenatide. He had two episodes of witnessed generalised tonic-clonic seizures. He was teetotal and was not taking diuretics. He was found to be hypomagnesaemic with normal serum calcium and normal 24-hour urinary magnesium excretion, excluding renal magnesium loss. It was concluded that his seizures were caused by nutritional hypomagnesaemia due to recurrent vomiting as a consequence of exenatide treatment.
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OBJECTIVE: To summarize and evaluate the available literature assessing the efficacy and safety of exenatide once weekly for the treatment of type 2 diabetes mellitus. DATA SOURCES: PubMed (1966-January 2012) and International Pha...
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OBJECTIVE: To summarize and evaluate the available literature assessing the efficacy and safety of exenatide once weekly for the treatment of type 2 diabetes mellitus. DATA SOURCES: PubMed (1966-January 2012) and International Pharmaceutical Abstracts (1969-January 2012) were searched using the term exenatide once weekly. Abstracts presented at the European Association for the Study of Diabetes Annual Meeting in 2011 and reference citations from publications were reviewed for inclusion. Eli Lilly and Company and Amylin Pharmaceuticals were contacted for additional unpublished information. STUDY SELECTION AND DATA EXTRACTION: All English-language articles and abstracts were evaluated for inclusion. All randomized controlled trials were included in the review. DATA SYNTHESIS: The efficacy and safety of exenatide once weekly has been evaluated as initial monotherapy and as add-on therapy to metformin, sulfonylureas, and thiazolidinediones in patients with uncontrolled type 2 diabetes for up to 3 years. Results from 6 randomized, comparator-controlled studies in over 3000 patients indicate that treatment with exenatide once weekly results in significant glycemic improvements and weight loss. Gastrointestinal adverse effects and injection site reactions are common, but rarely lead to drug discontinuation. CONCLUSIONS: Exenatide once weekly holds promise as a convenient, efficacious, and well-tolerated antihyperglycemic agent for the treatment of type 2 diabetes. Studies evaluating outcomes such as cardiovascular events or all-cause mortality with exenatide once weekly are lacking.
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Introduction: Anti-diabetes medication regimen adherence is a clinical challenge in elderly patients with type 2 diabetes (T2D) and other comorbidities associated with aging. Glucagon-like peptide-1 receptor agonists (GLP-1RA) the...
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Introduction: Anti-diabetes medication regimen adherence is a clinical challenge in elderly patients with type 2 diabetes (T2D) and other comorbidities associated with aging. Glucagon-like peptide-1 receptor agonists (GLP-1RA) therapies such as exenatide once weekly (QW), exenatide twice daily (BID), and liraglutide once daily (QD) are an increasingly used class of drugs with proven efficacy and tolerability. Real-world evidence on adherence to GLP-1RAs in elderly or disabled patients is limited. To further the understanding of this drug class, the current study examined medication adherence in Medicare patients aged >= 65 years with T2D initiating a GLP-1RA.
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AimsDapagliflozin and exenatide reduce body weight by differing mechanisms. Dual therapy with these agents reduces body weight, adipose tissue volume, glycaemia and systolic blood pressure (SBP) over 24weeks. Here, we examined the...
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AimsDapagliflozin and exenatide reduce body weight by differing mechanisms. Dual therapy with these agents reduces body weight, adipose tissue volume, glycaemia and systolic blood pressure (SBP) over 24weeks. Here, we examined these effects over 1year in obese adults without diabetes.
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Aims: To explore the effects of dual therapy with dapagliflozin and exenatide on body weight, body composition, glycaemic variables and systolic blood pressure (SBP) in obese adults without diabetes.
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