Effects of exenatide on weight and appetite in overweight adolescents and young adults with Prader‐Willi syndrome

Salehi, Peyman; Hsu, Isabel R.; Azen, Colleen; Mittelman, Steven D.; Geffner, Mitchell E.; Jeandron, Debra

doi:10.1111/ijpo.12131

Cited by 57 publications

(56 citation statements)

References 30 publications

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“…Although other pharmacological approaches to the management of weight and hyperphagia in individuals with PWS have been investigated, none has been effective in reducing hyperphagia. Only growth hormone has been shown to produce a moderate improvement in weight and body composition in some patients .…”

Section: Discussionmentioning

confidence: 99%

Effects of MetAP2 inhibition on hyperphagia and body weight in Prader–Willi syndrome: A randomized, double‐blind, placebo‐controlled trial

McCandless

Yanovski

Miller

et al. 2017

Diabetes Obesity Metabolism

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Aims There are no treatments for the extreme hyperphagia and obesity in Prader-Willi syndrome (PWS). The bestPWS trial assessed the efficacy, safety, and tolerability of the methionine aminopeptidase 2 (MetAP2) inhibitor, beloranib. Materials and Methods Participants with PWS (12–65 years) were randomly assigned (1:1:1) to biweekly placebo, 1.8 mg beloranib, or 2.4 mg beloranib injection for 26 weeks at 15 US sites. Coprimary endpoints were the changes in hyperphagia (measured by Hyperphagia Questionnaire for Clinical Trials [HQ-CT]; possible score 0–36) and weight by intention-to-treat. ClinicalTrials.gov registration: NCT02179151. Results 107 were included in the intention-to-treat analysis: placebo (n=34), 1.8 mg beloranib (n=36), or 2.4 mg beloranib (n=37). Improvement (reduction) in HQ-CT total score was greater in the 1.8 mg (mean difference −6.3, 95% CI −9.6 to −3.0; p=0.0003) and 2.4 mg beloranib groups (−7.0, 95% CI −10.5 to −3.6; p=0.0001) vs placebo. Compared to placebo, weight change was greater with 1.8 mg (mean difference −8.2%, 95% CI −10.8 to −5.6; p<0.0001) and 2.4 mg beloranib (−9.5%, 95% CI −12.1 to −6.8; p<0.0001). Injection site bruising was the most frequent adverse event with beloranib. Dosing was stopped early due to an imbalance in venous thrombotic events in beloranib-treated participants (two fatal events of pulmonary embolism and two events of deep vein thrombosis) compared to placebo. Conclusions MetAP2 inhibition with beloranib produced statistically significant and clinically meaningful improvements in hyperphagia-related behaviors and weight loss in participants with PWS. Although investigation of beloranib has ceased, inhibition of MetAP2 is a novel mechanism for treating hyperphagia and obesity.

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Section: Discussionmentioning

confidence: 99%

Effects of MetAP2 inhibition on hyperphagia and body weight in Prader–Willi syndrome: A randomized, double‐blind, placebo‐controlled trial

McCandless

Yanovski

Miller

et al. 2017

Diabetes Obesity Metabolism

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“…GLP1RAs decrease circulating ghrelin (Gagnon, Baggio, Drucker, & Brubaker, ). Use in PWS patients showed decreased appetite scores (Salehi et al, ), antidiabetogenic effects, and improved body mass index (BMI), particularly in the first 12 months of therapy, and the medication was safe when used in adults with PWS. In addition, it improved satiety and decreased circulating ghrelin in one patient (Fintini et al, ).…”

Section: Clinical Trialsmentioning

confidence: 99%

A multidisciplinary approach to the clinical management of Prader–Willi syndrome

Duis

Wattum

Scheimann

et al. 2019

Molec Gen & Gen Med

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Background Prader–Willi syndrome (PWS) is a complex neuroendocrine disorder affecting approximately 1/15,000–1/30,000 people. Unmet medical needs of individuals with PWS make it a rare disease that models the importance of multidisciplinary approaches to care with collaboration between academic centers, medical homes, industry, and parent organizations. Multidisciplinary clinics support comprehensive, patient‐centered care for individuals with complex genetic disorders and their families. Value comes from improved communication and focuses on quality family‐centered care. Methods Interviews with medical professionals, scientists, managed care experts, parents, and individuals with PWS were conducted from July 1 to December 1, 2016. Review of the literature was used to provide support. Results Data are presented based on consensus from these interviews by specialty focusing on unique aspects of care, research, and management. We have also defined the Center of Excellence beyond the multidisciplinary clinic. Conclusion Establishment of clinics motivates collaboration to provide evidence‐based new standards of care, increases the knowledge base including through randomized controlled trials, and offers an additional resource for the community. They have a role in global telemedicine, including to rural areas with few resources, and create opportunities for clinical work to inform basic and translational research. As a care team, we are currently charged with understanding the molecular basis of PWS beyond the known genetic cause; developing appropriate clinical outcome measures and biomarkers; bringing new therapies to change the natural history of disease; improving daily patient struggles, access to care, and caregiver burden; and decreasing healthcare load. Based on experience to date with a PWS multidisciplinary clinic, we propose a design for this approach and emphasize the development of “Centers of Excellence.” We highlight the dearth of evidence for management approaches creating huge gaps in care practices as a means to illustrate the importance of the collaborative environment and translational approaches.

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“…Salehi et al conducted the first longitudinal investigation of exenatide in patients with PWS . In an open‐label, nonrandomized trial, 10 adolescents and young adults with PWS and overweight/obesity (aged 14.7‐24.6 years) received 6 months of exenatide treatment.…”

Section: Resultsmentioning

confidence: 99%

Current and emerging therapies for managing hyperphagia and obesity in Prader‐Willi syndrome: A narrative review

et al. 2019

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Summary In early childhood, individuals with Prader‐Willi syndrome (PWS) experience excess weight gain and severe hyperphagia with food compulsivity, which often leads to early onset morbid obesity. Effective treatments for appetite suppression and weight control are currently unavailable for PWS. Our aim to further understand the pathogenesis of PWS led us to carry out a comprehensive search of the current and emerging therapies for managing hyperphagia and extreme weight gain in PWS. A literature search was performed using PubMed and the following keywords: “PWS” AND “therapy” OR “[drug name]”; reference lists, pharmaceutical websites, and the ClinicalTrials.gov registry were also reviewed. Articles presenting data from current standard treatments in PWS and also clinical trials of pharmacological agents in the pipeline were selected. Current standard treatments include dietary restriction/modifications, exercise, and growth hormone replacement, which appear to have limited efficacy for appetite and weight control in patients with PWS. The long‐term safety and effectiveness of bariatric surgery in PWS remains unknown. However, many promising pharmacotherapies are in development and, if approved, will bring much needed choices into the PWS pharmacological armamentarium. With the progress that is currently being made in our understanding of PWS, an effective treatment may not be far off.

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Effects of exenatide on weight and appetite in overweight adolescents and young adults with Prader‐Willi syndrome

Cited by 57 publications

References 30 publications

Effects of MetAP2 inhibition on hyperphagia and body weight in Prader–Willi syndrome: A randomized, double‐blind, placebo‐controlled trial

Effects of MetAP2 inhibition on hyperphagia and body weight in Prader–Willi syndrome: A randomized, double‐blind, placebo‐controlled trial

A multidisciplinary approach to the clinical management of Prader–Willi syndrome

Current and emerging therapies for managing hyperphagia and obesity in Prader‐Willi syndrome: A narrative review

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