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<div class="multiple-results-actions " role="region" aria-label="save, email, send to">
<button id="save-results-panel-trigger"
type="button"
class="save-results save-results-panel-trigger"
aria-expanded="false"
aria-controls="save-action-panel"
data-ga-category="save_share"
data-ga-action="save"
data-ga-label="open">
Save
</button><button id="email-results-panel-trigger"
type="button"
class="email-results email-results-panel-trigger"
aria-expanded="false"
aria-controls="email-action-panel"
data-ga-category="save_share"
data-ga-action="email"
data-ga-label="open">
Email
</button><div class="more-actions dropdown-block"><button id="more-actions-trigger"
type="button"
class="trigger more-actions-trigger"
ref="linksrc=show_moreactions_btn"
aria-label="Send to"
aria-controls="more-actions-dropdown">Send to</button><div id="more-actions-dropdown" class="dropdown dropdown-container" hidden><div class="content"><ul class="more-actions-links"><li><a class="clipboard-panel-trigger dropdown-block-link "
href="#"
role="button"
data-ga-category="save_share"
data-ga-action="clipboard"
data-ga-label="send">
Clipboard
</a></li><li><a role="button" class="dropdown-block-link bibliography-trigger-target" href="https://account.ncbi.nlm.nih.gov/?back_url=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F33137293%2F%23open-bibliography-panel">My Bibliography</a></li><li><a role="button" class="dropdown-block-link collections-trigger-target" href="https://account.ncbi.nlm.nih.gov/?back_url=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F33137293%2F%23open-collections-panel">Collections</a></li><li><a role="button" class="citation-manager-panel-trigger dropdown-block-link citation-manager-trigger-target" href="#">Citation manager</a></li></ul></div></div></div>
</div>
<div class="display-options" data-format-key="format"
data-default-format-value="abstract"
data-current-format-value="abstract" role="region">
<button
class="trigger usa-button"
title="Change format"
data-ga-category="display_options"
data-ga-action="display_options_dialog">
<span class="button-label">Display options</span>
</button>
<div class="dropdown" hidden>
<div class="title">
Display options
</div>
<div class="content">
<div class="format-container">
<span class="option-label">
Format
</span>
<select name="format" data-initial-value="abstract" aria-label="Display format" id="article-display-format">
<option value="abstract">Abstract</option>
<option value="pubmed">PubMed</option>
<option value="pmid">PMID</option>
</select>
</div>
</div>
</div>
</div>
<input type="hidden" name="csrfmiddlewaretoken" value="fCm5JC6f7WQI3sfiS8yLKK2DioQzNrEqwp6amszBHxDcXTl8vrbNeSyhQsyLG2cK">
</div>
</div>
</div>
<div id="article-panels-container" class="article-panels-container">
<div id="save-action-panel" class="save-action-panel action-panel" aria-hidden="true">
<div class="inner-wrap">
<h2 class="action-panel-heading">
Save citation to file
</h2>
<form id="save-action-panel-form"
class="action-panel-content action-form"
action="/results-export-ids/"
data-by-search-action="/results-export-search-data/"
data-by-ids-action="/results-export-ids/"
method="post"
data-by-search-method="post"
data-by-ids-method="post">
<input type="hidden" name="csrfmiddlewaretoken" value="fCm5JC6f7WQI3sfiS8yLKK2DioQzNrEqwp6amszBHxDcXTl8vrbNeSyhQsyLG2cK">
<div class="action-panel-control-wrap">
<label for="save-action-format" class="action-panel-label">
Format:
</label>
<select id="save-action-format" name="results-format" class="action-panel-selector">
<option value="summary-text">Summary (text)</option>
<option value="pubmed-text">PubMed</option>
<option value="pmid">PMID</option>
<option value="abstract">Abstract (text)</option>
<option value="csv">CSV</option>
</select>
</div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Saving..."
data-ga-category="save_share"
data-ga-action="save"
data-ga-label="save">
Create file
</button>
<button class="action-panel-cancel"
aria-label="Close 'Save citations to file' panel"
ref="linksrc=close_save_panel"
aria-controls="save-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="save"
data-ga-label="cancel">
Cancel
</button>
</div>
</form>
</div>
</div>
<div id="email-action-panel"
class="email-action-panel action-panel"
aria-hidden="true"
data-recaptcha-script-url="https://www.recaptcha.net/recaptcha/enterprise.js?render=explicit&onload=onloadCaptchaCallback"
data-recaptcha-enabled="true">
<div class="inner-wrap">
<h2 class="action-panel-heading">
Email citation
</h2>
<form id="email-action-panel-form"
class="action-panel-content action-form"
action="/send-email/"
data-by-search-action="/results-export-email-by-search-data/"
data-by-ids-action="/send-email/"
data-by-search-method="post"
data-by-ids-method="post"
method="post"
>
<input type="hidden" name="csrfmiddlewaretoken" value="fCm5JC6f7WQI3sfiS8yLKK2DioQzNrEqwp6amszBHxDcXTl8vrbNeSyhQsyLG2cK">
<div class="action-panel-control-wrap">
<span class="action-panel-label">
Subject:
</span>
<span class="email-subject" id="email-subject" aria-label="Email subject">1 selected item: 33137293 - PubMed</span>
<input type="hidden" name="email-subject" value="1 selected item: 33137293"/>
<input type="hidden" name="email-subject-hash" value="2d6141abe9ede45bfa7c55eaddfda55b2e07312d824de51e2372751a6d49c259"/>
</div>
<div class="action-panel-control-wrap">
<label for="email-to" class="action-panel-label required-field-asterisk">
To:
</label>
<input type="email" aria-label="Recipient Email Address" placeholder="email@example.com" id="email-to" class="email-to" pattern="^[a-zA-Z0-9_.+-]+@[a-zA-Z0-9-]+\.[a-zA-Z0-9-.]+$" maxlength="100" required>
</div>
<div class="action-panel-control-wrap">
<label for="email-from" class="action-panel-label">
From:
</label>
<input type="email" aria-label="Sender Email Address" placeholder="email@example.com" id="email-from" class="email-from" pattern="^[a-zA-Z0-9_.+-]+@[a-zA-Z0-9-]+\.[a-zA-Z0-9-.]+$" maxlength="256">
</div>
<div class="action-panel-control-wrap">
<label for="email-citation-format" class="action-panel-label">
Format:
</label>
<select id="email-citation-format" name="citation-format" class="action-panel-selector email-citation-format">
<option selected="selected" value="summary">Summary</option>
<option value="summary-text">Summary (text)</option>
<option value="abstract">Abstract</option>
<option value="abstract-text">Abstract (text)</option>
</select>
</div>
<div class="include-supplemental-container">
<input type="checkbox" aria-label="Include MeSH and other data" name="include-supplemental" id="email-include-supplemental" class="email-include-supplemental">
<label for="email-include-supplemental" class="email-include-supplemental-label">MeSH and other data</label>
</div>
<div class="form-field recaptcha ">
<div class="g-recaptcha" id="id-recaptcha" data-sitekey="6LfsWHMdAAAAAClKbtOpjQ2pMjgsGxvv7NdZW9uI"></div>
</div>
<div id="captcha-error-message" class="usa-input-error-message captcha-validation-message" role="alert"></div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Sending..."
data-ga-category="save_share"
data-ga-action="email"
data-ga-label="send">
Send email
</button>
<button class="action-panel-cancel"
aria-label="Close 'Email citations' panel"
ref="linksrc=close_email_panel"
aria-controls="email-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="email"
data-ga-label="cancel">
Cancel
</button>
</div>
<input type="hidden" name="email-search-details" value="" />
<input type="hidden" name="email-search-details-hash" value="0e42663a6c3bd85498fcb88798998fed7bfdc45d457db35281e41afe13cc0524" />
</form>
</div>
</div>
<div id="collections-action-panel"
class="collections-action-panel action-panel in-progress-dots-panel"
aria-hidden="true"
data-collections-open-panel-enabled="false"
data-collections-open-panel-url-hash="#open-collections-panel">
<div class="inner-wrap">
<h3 class="action-panel-heading">
Add to Collections
</h3>
<form id="collections-action-panel-form"
class="collections-action-panel-form action-panel-content action-form action-panel-smaller-selectors"
data-existing-collections-url="/list-existing-collections/"
data-add-to-existing-collection-url="/add-to-existing-collection/"
data-create-and-add-to-new-collection-url="/create-and-add-to-new-collection/"
data-get-article-ids-by-search-url="/get-article-ids-by-search/"
data-myncbi-max-collection-name-length="100"
data-add-to-collection-max-amount="1000"
data-collections-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/">
<input type="hidden" name="csrfmiddlewaretoken" value="fCm5JC6f7WQI3sfiS8yLKK2DioQzNrEqwp6amszBHxDcXTl8vrbNeSyhQsyLG2cK">
<div class="choice-group" role="radiogroup">
<ul class="radio-group-items">
<li>
<input type="radio"
id="collections-action-panel-new"
class="collections-new"
name="collections"
value="new"
data-ga-category="save_share"
data-ga-action="collections"
data-ga-label="collections_radio_new">
<label for="collections-action-panel-new">Create a new collection</label>
</li>
<li>
<input type="radio"
id="collections-action-panel-existing"
class="collections-existing"
name="collections"
value="existing"
checked="true"
data-ga-category="save_share"
data-ga-action="collections"
data-ga-label="collections_radio_existing">
<label for="collections-action-panel-existing">Add to an existing collection</label>
</li>
</ul>
</div>
<div class="controls-wrapper">
<div class="action-panel-control-wrap new-collections-controls">
<label for="collections-action-panel-add-to-new" class="action-panel-label required-field-asterisk">
Name your collection:
</label>
<input
type="text"
name="add-to-new-collection"
id="collections-action-panel-add-to-new"
class="collections-action-add-to-new"
pattern="[^&quot;&amp;=&lt;&gt;\/]*" title="The following characters are not allowed in the Name field: &quot;&amp;=&lt;&gt;/"
maxlength="100"
data-ga-category="save_share"
data-ga-action="create_collection"
data-ga-label="non_favorties_collection">
<div class="collections-new-name-too-long usa-input-error-message selection-validation-message">
Name must be less than 100 characters
</div>
</div>
<div class="action-panel-control-wrap existing-collections-controls">
<label for="collections-action-panel-add-to-existing" class="action-panel-label">
Choose a collection:
</label>
<select id="collections-action-panel-add-to-existing"
class="action-panel-selector collections-action-add-to-existing"
data-ga-category="save_share"
data-ga-action="select_collection"
data-ga-label="($('#collections-action-add-to-existing').val() === 'Favorites') ? 'Favorites' : 'non_favorites_collection'">
</select>
<div class="collections-retry-load-on-error usa-input-error-message selection-validation-message">
Unable to load your collection due to an error<br>
<a href="#">Please try again</a>
</div>
</div>
</div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Adding..."
data-pinger-ignore
data-ga-category="save_share"
data-ga-action="collections"
data-ga-label="add">
Add
</button>
<button class="action-panel-cancel"
aria-label="Close 'Add to Collections' panel"
ref="linksrc=close_collections_panel"
aria-controls="collections-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="collections"
data-ga-label="cancel">
Cancel
</button>
</div>
</form>
</div>
</div>
<div id="bibliography-action-panel"
class="bibliography-action-panel action-panel in-progress-dots-panel"
aria-hidden="true"
data-bibliography-open-panel-enabled="false"
data-bibliography-open-panel-url-hash="#open-bibliography-panel">
<div class="inner-wrap">
<h3 class="action-panel-heading">
Add to My Bibliography
</h3>
<form id="bibliography-action-panel-form"
class="bibliography-action-panel-form action-panel-content action-form action-panel-smaller-selectors"
data-add-to-bibliography-max-amount="100"
data-add-to-bibliography-batch-size="10"
data-bibliography-delegates-url="/list-bibliography-delegates/"
data-add-to-bibliography-url="/add-to-bibliography/"
data-get-article-ids-by-search-url="/get-article-ids-by-search/"
data-mybib-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/mybibliography/">
<input type="hidden" name="csrfmiddlewaretoken" value="fCm5JC6f7WQI3sfiS8yLKK2DioQzNrEqwp6amszBHxDcXTl8vrbNeSyhQsyLG2cK">
<div class="action-panel-control-wrap bibliographies-controls">
<div class="choice-group">
<ul class="bibliographies-action-add radio-group-items">
<li>
<input name="bibliography" id="my-bibliography" class="my-bibliography" type="radio" checked/>
<label for="my-bibliography">My Bibliography</label>
</li>
</ul>
</div>
</div>
<div class="bibliographies-retry-load-on-error usa-input-error-message selection-validation-message">
Unable to load your delegates due to an error<br>
<a href="#">Please try again</a>
</div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Adding..."
data-pinger-ignore>
Add
</button>
<button class="action-panel-cancel"
aria-label="Close 'Add to bibliography' panel"
ref="linksrc=close_bibliography_panel"
aria-controls="bibliography-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="mybib"
data-ga-label="cancel">
Cancel
</button>
</div>
</form>
</div>
</div>
<div id="saved-search-action-panel" class="saved-search-action-panel action-panel " aria-hidden="true"
data-saved-search-open-panel-enabled="false"
data-saved-search-open-panel-url-hash="#open-saved-search-panel">
<div class="inner-wrap">
<h2 class="action-panel-heading">
Your saved search
</h2>
<form id="saved-search-action-panel-form"
class="saved-search-action-panel-form action-panel-content action-form"
data-create-saved-search-url="/create-saved-search/"
data-try-search-terms-url="/try-search-term/"
data-saved-search-root-url="https://www.ncbi.nlm.nih.gov/myncbi/searches/">
<input type="hidden" name="csrfmiddlewaretoken" value="fCm5JC6f7WQI3sfiS8yLKK2DioQzNrEqwp6amszBHxDcXTl8vrbNeSyhQsyLG2cK">
<div class="action-panel-control-wrap">
<label for="saved-search-name" class="action-panel-label saved-search-name-label required-field-asterisk">
Name of saved search:
</label>
<input maxlength="200"
type="text"
name="saved-search-name"
id="saved-search-name"
class="saved-search-name"
value=""
required
pattern="[^&quot;&amp;=&lt;&gt;\/]*" title="The following characters are not allowed in the Name field: &quot;&amp;=&lt;&gt;/">
</div>
<div class="action-panel-control-wrap">
<label for="saved-search-term" class="action-panel-label required-field-asterisk">
Search terms:
</label>
<textarea name="saved-search-term" id="saved-search-term" class="saved-search-term" required></textarea>
</div>
<div class="test-search-term-wrap">
<a href="#" class="try-search-term">Test search terms</a>
</div>
<div class="choice-group action-panel-extra-margin-top">
<span class="action-panel-label" id="fieldset-label">
Would you like email updates of new search results?
</span>
<fieldset id="saved-search-alert" aria-describedby="fieldset-label">
<legend class="usa-sr-only">Saved Search Alert Radio Buttons</legend>
<ul class="radio-group-items">
<li>
<input type="radio" id="saved-search-alert-yes" class="saved-search-alert-yes" name="saved-search-alert" value="yes" checked>
<label for="saved-search-alert-yes" class="action-panel-label">Yes</label>
</li>
<li>
<input aria-label="No radio input" type="radio" id="saved-search-alert-no" class="saved-search-alert-no" name="saved-search-alert" value="no">
<label for="saved-search-alert-no" class="action-panel-label">No</label>
</li>
</ul>
</fieldset>
</div>
<div class="alert-schedule-wrap">
<div class="action-panel-control-wrap">
<label class="action-panel-label">
Email:
</label>
<span aria-label="Email address" id="saved-search-email" class="action-panel-label"><span class="action-panel-label-bold"></span> (<a class="myncbi-account-settings" href="https://www.ncbi.nlm.nih.gov/account/settings/">change</a>)</span>
</div>
<div class="action-panel-control-wrap action-panel-extra-margin-top">
<label for="saved-search-frequency" class="action-panel-label">
Frequency:
</label>
<select id="saved-search-frequency" class="no-border-panel-selector saved-search-frequency">
<option value="monthly">Monthly</option>
<option value="weekly">Weekly</option>
<option value="daily">Daily</option>
</select>
</div>
<div class="action-panel-control-wrap saved-search-monthly-additional">
<label for="saved-search-monthly-on-day" class="action-panel-label">
Which day?
</label>
<select id="saved-search-monthly-on-day" class="no-border-panel-selector">
<option value="Sunday">The first Sunday</option>
<option value="Monday">The first Monday</option>
<option value="Tuesday">The first Tuesday</option>
<option value="Wednesday">The first Wednesday</option>
<option value="Thursday">The first Thursday</option>
<option value="Friday">The first Friday</option>
<option value="Saturday">The first Saturday</option>
<option value="day">The first day</option>
<option value="weekday">The first weekday</option>
</select>
</div>
<div class="action-panel-control-wrap saved-search-weekly-additional">
<label for="saved-search-weekly-on-day" class="action-panel-label">
Which day?
</label>
<select id="saved-search-weekly-on-day" class="no-border-panel-selector saved-search-weekly-on-day">
<option value="Sunday">Sunday</option>
<option value="Monday">Monday</option>
<option value="Tuesday">Tuesday</option>
<option value="Wednesday">Wednesday</option>
<option value="Thursday">Thursday</option>
<option value="Friday">Friday</option>
<option value="Saturday">Saturday</option>
</select>
</div>
<div class="action-panel-control-wrap">
<label for="saved-search-report" class="action-panel-label">
Report format:
</label>
<select id="saved-search-report" class="no-border-panel-selector saved-search-report">
<option value="DocSum">Summary</option>
<option value="DocSumText">Summary (text)</option>
<option value="Abstract">Abstract</option>
<option value="AbstractText">Abstract (text)</option>
<option value="MEDLINE">PubMed</option>
</select>
</div>
<div class="action-panel-control-wrap">
<label for="saved-search-amount" class="action-panel-label">
Send at most:
</label>
<select id="saved-search-amount" class="no-border-panel-selector saved-search-amount">
<option value="1">1 item</option>
<option value="5" selected>5 items</option>
<option value="10">10 items</option>
<option value="20">20 items</option>
<option value="50">50 items</option>
<option value="100">100 items</option>
<option value="200">200 items</option>
</select>
</div>
<div>
<input type="checkbox" id="saved-search-send-if-no-result" class="saved-search-send-if-no-result" name="saved-search-send-if-no-result">
<label for="saved-search-send-if-no-result" class="action-panel-label smaller-checkbox">
Send even when there aren't any new results
</label>
</div>
<div class="action-panel-control-wrap option-text-in-email-wrap">
<label for="saved-search-email-text" class="action-panel-label">
Optional text in email:
</label>
<textarea name="saved-search-email-text"
id="saved-search-email-text"
class="saved-search-email-text"></textarea>
</div>
</div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Saving..."
data-ga-category="save_share"
data-ga-action="alert"
data-ga-label="save">
Save
</button>
<button class="action-panel-cancel"
aria-label="Close 'Your saved search' panel"
ref="linksrc=close_saved_search_panel"
aria-controls="saved-search-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="alert"
data-ga-label="cancel">
Cancel
</button>
</div>
</form>
</div>
</div>
<div id="citation-manager-action-panel" class="citation-manager-action-panel action-panel" aria-hidden="true">
<div class="inner-wrap">
<h2 class="action-panel-heading">
Create a file for external citation management software
</h2>
<form id="citation-manager-action-panel-form"
class="action-panel-content action-form"
action="/results-export-ids/"
data-by-search-action="/results-export-search-data/"
data-by-ids-action="/results-export-ids/"
method="post"
data-by-search-method="post"
data-by-ids-method="post">
<input type="hidden" name="csrfmiddlewaretoken" value="fCm5JC6f7WQI3sfiS8yLKK2DioQzNrEqwp6amszBHxDcXTl8vrbNeSyhQsyLG2cK">
<input name="results-format" type="hidden" value="pubmed"/>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Sending..."
data-ga-category="save_share"
data-ga-action="citation_manager"
data-ga-label="save">
Create file
</button>
<button class="action-panel-cancel"
aria-label="Close 'Send citations to citation manager' panel"
ref="linksrc=close_citation_manager_panel"
aria-controls="citation-manager-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="citation_manager"
data-ga-label="cancel">
Cancel
</button>
</div>
</form>
</div>
</div>
<div id="rss-action-panel" class="rss-action-panel action-panel " aria-hidden="true">
<div class="inner-wrap">
<h2 class="action-panel-heading">
Your RSS Feed
</h2>
<form id="rss-action-panel-form"
class="rss-action-panel-form action-panel-content action-form"
data-create-rss-feed-url="/create-rss-feed-url/"
data-search-form-term-value="">
<input type="hidden" name="csrfmiddlewaretoken" value="fCm5JC6f7WQI3sfiS8yLKK2DioQzNrEqwp6amszBHxDcXTl8vrbNeSyhQsyLG2cK">
<div class="action-panel-control-wrap">
<label for="rss-name" class="action-panel-label required-field-asterisk">
Name of RSS Feed:
</label>
<input maxlength="200"
placeholder="Name"
type="text"
name="rss-name"
id="rss-name"
class="rss-name"
value=''
required
pattern="[^&quot;&amp;=&lt;&gt;\/]*" title="The following characters are not allowed in the Name field: &quot;&amp;=&lt;&gt;/">
</div>
<div class="rss-limit-wrap">
<div class="action-panel-control-wrap action-panel-extra-margin-top">
<label for="rss-limit" class="action-panel-label">
Number of items displayed:
</label>
<select id="rss-limit" class="no-border-panel-selector rss-limit">
<option value="5">5</option>
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Efficacy and safety of setmelanotide, an MC4R agonist, in individuals with severe obesity due to LEPR or POMC deficiency: single-arm, open-label, multicentre, phase 3 trials
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11
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12
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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6
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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6
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
href="/?term=Wabitsch+M&amp;cauthor_id=33137293"
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data-ga-label="Martin Wabitsch">Martin Wabitsch</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Division of Pediatric Endocrinology and Diabetes, Center for Rare Endocrine Diseases, Department of Pediatrics and Adolescent Medicine, University of Ulm, Ulm, Germany. Electronic address: martin.wabitsch@uniklinik-ulm.de." href="#full-view-affiliation-13" ref="linksrc=author_aff">
13
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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14
</a></sup><span class="semicolon">;&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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<strong class="title">Setmelanotide POMC and LEPR Phase 3 Trial Investigators</strong>:
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data-ga-label="Christian Denzer">Christian Denzer</a><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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data-ga-label="Julia von Schnurbein">Julia von Schnurbein</a><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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data-ga-label="Ozair Abawi">Ozair Abawi</a><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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data-ga-label="Ulrike Blume-Peytavi">Ulrike Blume-Peytavi</a><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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data-ga-label="Knut Mai">Knut Mai</a><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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data-ga-label="James M Swain">James M Swain</a><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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data-ga-label="Goujun Yuan">Goujun Yuan</a><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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data-ga-label="Peter Kühnen">Peter Kühnen</a></span>
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<div class="affiliations">
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Affiliations
</h3>
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<li data-affiliation-id="full-view-affiliation-1"
id="full-view-affiliation-1"
><sup class="key">1</sup> Assistance Publique Hôpitaux de Paris, Nutrition Department, Pitié-Salpêtrière Hospital, Paris, France; Sorbonne Université, INSERM, NutriOmics Research Unit, Paris, France.</li>
<li data-affiliation-id="full-view-affiliation-2"
id="full-view-affiliation-2"
><sup class="key">2</sup> Division of Pediatric Endocrinology, Department of Pediatrics, Sophia Children&#x27;s Hospital and Obesity Center CGG, Erasmus University Medical Center, Rotterdam, Netherlands.</li>
<li data-affiliation-id="full-view-affiliation-3"
id="full-view-affiliation-3"
><sup class="key">3</sup> Department of Pediatrics and Pediatric Endocrinology, Universidad Autónoma de Madrid, University Hospital Niño Jesús, CIBER &quot;Fisiopatología de la obesidad y nutrición&quot; (CIBEROBN), Instituto de Salud Carlos III, IMDEA Institute, Madrid, Spain.</li>
<li data-affiliation-id="full-view-affiliation-4"
id="full-view-affiliation-4"
><sup class="key">4</sup> Peel Memorial Hospital, Toronto, ON, Canada.</li>
<li data-affiliation-id="full-view-affiliation-5"
id="full-view-affiliation-5"
><sup class="key">5</sup> Department of Pediatrics and Department of Medicine, Columbia University, New York, NY, USA.</li>
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id="full-view-affiliation-6"
><sup class="key">6</sup> Rhythm Pharmaceuticals, Boston, MA, USA.</li>
<li data-affiliation-id="full-view-affiliation-7"
id="full-view-affiliation-7"
><sup class="key">7</sup> Department of Pediatric and Adolescent Endocrinology, Ghent University Hospital, Ghent, Belgium.</li>
<li data-affiliation-id="full-view-affiliation-8"
id="full-view-affiliation-8"
><sup class="key">8</sup> Wellcome-MRC Institute of Metabolic Science and NIHR Cambridge Biomedical Research Centre, University of Cambridge, Cambridge, UK.</li>
<li data-affiliation-id="full-view-affiliation-9"
id="full-view-affiliation-9"
><sup class="key">9</sup> Université de la Réunion, Unité Transversale de Nutrition Clinique, CHU de la Réunion, Réunion, France.</li>
<li data-affiliation-id="full-view-affiliation-10"
id="full-view-affiliation-10"
><sup class="key">10</sup> Division of Pediatric Endocrinology and Diabetes, Center for Rare Endocrine Diseases, Department of Pediatrics and Adolescent Medicine, University of Ulm, Ulm, Germany.</li>
<li data-affiliation-id="full-view-affiliation-11"
id="full-view-affiliation-11"
><sup class="key">11</sup> Institute for Experimental Pediatric Endocrinology, Charité Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany; Department for Pediatric Endocrinology and Diabetology, Charité Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.</li>
<li data-affiliation-id="full-view-affiliation-12"
id="full-view-affiliation-12"
><sup class="key">12</sup> HonorHealth Bariatric Center, Scottsdale, AZ, USA.</li>
<li data-affiliation-id="full-view-affiliation-13"
id="full-view-affiliation-13"
><sup class="key">13</sup> Division of Pediatric Endocrinology and Diabetes, Center for Rare Endocrine Diseases, Department of Pediatrics and Adolescent Medicine, University of Ulm, Ulm, Germany. Electronic address: martin.wabitsch@uniklinik-ulm.de.</li>
<li data-affiliation-id="full-view-affiliation-14"
id="full-view-affiliation-14"
><sup class="key">14</sup> Institute for Experimental Pediatric Endocrinology, Charité Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany. Electronic address: peter.kuehnen@charite.de.</li>
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<div class="publication-type" >Clinical Trial</div>
<h1 class="heading-title">
Efficacy and safety of setmelanotide, an MC4R agonist, in individuals with severe obesity due to LEPR or POMC deficiency: single-arm, open-label, multicentre, phase 3 trials
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<span class="authors-list-item "><span class="full-name">Karine Clément</span><span class="citation-separator">&nbsp;et al.</span></span>
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Lancet Diabetes Endocrinol<span class="citation-separator">.</span>
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<span class="citation-year">2020 Dec</span><span class="citation-separator">.</span>
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<span class="citation-doi">
doi: 10.1016/S2213-8587(20)30364-8.
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<span class="secondary-date">
Epub 2020 Oct 30.
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Authors
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<span class="authors-list-item "><a class="full-name"
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data-ga-label="Karine Clément">Karine Clément</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Assistance Publique Hôpitaux de Paris, Nutrition Department, Pitié-Salpêtrière Hospital, Paris, France; Sorbonne Université, INSERM, NutriOmics Research Unit, Paris, France." href="#short-view-affiliation-1" ref="linksrc=author_aff">
1
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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2
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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3
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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4
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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5
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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6
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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7
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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8
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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9
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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6
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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10
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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1
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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11
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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12
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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6
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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6
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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data-ga-label="Martin Wabitsch">Martin Wabitsch</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Division of Pediatric Endocrinology and Diabetes, Center for Rare Endocrine Diseases, Department of Pediatrics and Adolescent Medicine, University of Ulm, Ulm, Germany. Electronic address: martin.wabitsch@uniklinik-ulm.de." href="#short-view-affiliation-13" ref="linksrc=author_aff">
13
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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14
</a></sup><span class="semicolon">;&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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data-ga-label="Goujun Yuan">Goujun Yuan</a><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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><sup class="key">1</sup> Assistance Publique Hôpitaux de Paris, Nutrition Department, Pitié-Salpêtrière Hospital, Paris, France; Sorbonne Université, INSERM, NutriOmics Research Unit, Paris, France.</li>
<li data-affiliation-id="short-view-affiliation-2"
id="short-view-affiliation-2"
><sup class="key">2</sup> Division of Pediatric Endocrinology, Department of Pediatrics, Sophia Children&#x27;s Hospital and Obesity Center CGG, Erasmus University Medical Center, Rotterdam, Netherlands.</li>
<li data-affiliation-id="short-view-affiliation-3"
id="short-view-affiliation-3"
><sup class="key">3</sup> Department of Pediatrics and Pediatric Endocrinology, Universidad Autónoma de Madrid, University Hospital Niño Jesús, CIBER &quot;Fisiopatología de la obesidad y nutrición&quot; (CIBEROBN), Instituto de Salud Carlos III, IMDEA Institute, Madrid, Spain.</li>
<li data-affiliation-id="short-view-affiliation-4"
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><sup class="key">4</sup> Peel Memorial Hospital, Toronto, ON, Canada.</li>
<li data-affiliation-id="short-view-affiliation-5"
id="short-view-affiliation-5"
><sup class="key">5</sup> Department of Pediatrics and Department of Medicine, Columbia University, New York, NY, USA.</li>
<li data-affiliation-id="short-view-affiliation-6"
id="short-view-affiliation-6"
><sup class="key">6</sup> Rhythm Pharmaceuticals, Boston, MA, USA.</li>
<li data-affiliation-id="short-view-affiliation-7"
id="short-view-affiliation-7"
><sup class="key">7</sup> Department of Pediatric and Adolescent Endocrinology, Ghent University Hospital, Ghent, Belgium.</li>
<li data-affiliation-id="short-view-affiliation-8"
id="short-view-affiliation-8"
><sup class="key">8</sup> Wellcome-MRC Institute of Metabolic Science and NIHR Cambridge Biomedical Research Centre, University of Cambridge, Cambridge, UK.</li>
<li data-affiliation-id="short-view-affiliation-9"
id="short-view-affiliation-9"
><sup class="key">9</sup> Université de la Réunion, Unité Transversale de Nutrition Clinique, CHU de la Réunion, Réunion, France.</li>
<li data-affiliation-id="short-view-affiliation-10"
id="short-view-affiliation-10"
><sup class="key">10</sup> Division of Pediatric Endocrinology and Diabetes, Center for Rare Endocrine Diseases, Department of Pediatrics and Adolescent Medicine, University of Ulm, Ulm, Germany.</li>
<li data-affiliation-id="short-view-affiliation-11"
id="short-view-affiliation-11"
><sup class="key">11</sup> Institute for Experimental Pediatric Endocrinology, Charité Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany; Department for Pediatric Endocrinology and Diabetology, Charité Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.</li>
<li data-affiliation-id="short-view-affiliation-12"
id="short-view-affiliation-12"
><sup class="key">12</sup> HonorHealth Bariatric Center, Scottsdale, AZ, USA.</li>
<li data-affiliation-id="short-view-affiliation-13"
id="short-view-affiliation-13"
><sup class="key">13</sup> Division of Pediatric Endocrinology and Diabetes, Center for Rare Endocrine Diseases, Department of Pediatrics and Adolescent Medicine, University of Ulm, Ulm, Germany. Electronic address: martin.wabitsch@uniklinik-ulm.de.</li>
<li data-affiliation-id="short-view-affiliation-14"
id="short-view-affiliation-14"
><sup class="key">14</sup> Institute for Experimental Pediatric Endocrinology, Charité Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany. Electronic address: peter.kuehnen@charite.de.</li>
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Abstract
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<p>
<strong class="sub-title">
Background:
</strong>
The melanocortin 4 receptor (MC4R), a component of the leptin-melanocortin pathway, plays a part in bodyweight regulation. Severe early-onset obesity can be caused by biallelic variants in genes that affect the MC4R pathway. We report the results from trials of the MC4R agonist setmelanotide in individuals with severe obesity due to either pro-opiomelanocortin (POMC) deficiency obesity or leptin receptor (LEPR) deficiency obesity.
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Methods:
</strong>
These single-arm, open-label, multicentre, phase 3 trials were done in ten hospitals across Canada, the USA, Belgium, France, Germany, the Netherlands, and the UK. Participants aged 6 years or older with POMC or LEPR deficiency obesity received open-label setmelanotide for 12 weeks. Participants with at least 5 kg weight loss (or ≥5% if weighing &lt;100 kg at baseline) entered an 8-week placebo-controlled withdrawal sequence (including 4 weeks each of blinded setmelanotide and placebo treatment) followed by 32 additional weeks of open-label treatment. The primary endpoint, which was assessed in participants who received at least one dose of study medication and had a baseline assessment (full analysis set), was the proportion of participants with at least 10% weight loss compared with baseline at approximately 1 year. A key secondary endpoint was mean percentage change in the most hunger score of the 11-point Likert-type scale at approximately 1 year on the therapeutic dose, which was assessed in a subset of participants aged 12 years or older in the full analysis set who demonstrated at least 5 kg weight loss (or ≥5% in paediatric participants if baseline bodyweight was &lt;100 kg) over the 12-week open-label treatment phase and subsequently proceeded into the placebo-controlled withdrawal sequence, regardless of later disposition. These studies are registered with ClinicalTrials.gov, <a href="http://clinicaltrials.gov/show/NCT02896192" title="See in ClinicalTrials.gov">NCT02896192</a> and <a href="http://clinicaltrials.gov/show/NCT03287960" title="See in ClinicalTrials.gov">NCT03287960</a>.
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<p>
<strong class="sub-title">
Findings:
</strong>
Between Feb 14, 2017, and Sept 7, 2018, ten participants were enrolled in the POMC trial and 11 participants were enrolled in the LEPR trial, and included in the full analysis and safety sets. Eight (80%) participants in the POMC trial and five (45%) participants in the LEPR trial achieved at least 10% weight loss at approximately 1 year. The mean percentage change in the most hunger score was -27·1% (n=7; 90% CI -40·6 to -15·0; p=0·0005) in the POMC trial and -43·7% (n=7; -54·8 to -29·1; p&lt;0·0001) in the LEPR trial. The most common adverse events were injection site reaction and hyperpigmentation, which were reported in all ten participants in the POMC trial; nausea was reported in five participants and vomiting in three participants. In the LEPR trial, the most commonly reported treatment-related adverse events were injection site reaction in all 11 participants, skin disorders in five participants, and nausea in four participants. No serious treatment-related adverse events occurred in both trials.
</p>
<p>
<strong class="sub-title">
Interpretation:
</strong>
Our results support setmelanotide for the treatment of obesity and hyperphagia caused by POMC or LEPR deficiency.
</p>
<p>
<strong class="sub-title">
Funding:
</strong>
Rhythm Pharmaceuticals.
</p>
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Setmelanotide: what does it mean for clinical care of patients with obesity?
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<span class="docsum-authors full-authors">Ryan DH.</span>
<span class="docsum-authors short-authors">Ryan DH.</span>
<span class="docsum-journal-citation full-journal-citation">Lancet Diabetes Endocrinol. 2020 Dec;8(12):933-935. doi: 10.1016/S2213-8587(20)30366-1. Epub 2020 Oct 30.</span>
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MeSH terms
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Obesity / drug therapy*
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</div>
<div id="substances" class="substances keywords-section">
<h2 class="title">
Substances
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