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Available in 20 languages" > <label id="p-lang-btn-label" for="p-lang-btn-checkbox" class="vector-dropdown-label cdx-button cdx-button--fake-button cdx-button--fake-button--enabled cdx-button--weight-quiet cdx-button--action-progressive mw-portlet-lang-heading-20" aria-hidden="true" ><span class="vector-icon mw-ui-icon-language-progressive mw-ui-icon-wikimedia-language-progressive"></span> <span class="vector-dropdown-label-text">20 languages</span> </label> <div class="vector-dropdown-content"> <div class="vector-menu-content"> <ul class="vector-menu-content-list"> <li class="interlanguage-link interwiki-ar mw-list-item"><a href="https://ar.wikipedia.org/wiki/%D8%A8%D8%A8%D8%AA%D9%8A%D8%AF_%D8%B4%D8%A8%D9%8A%D9%87_%D8%A8%D8%A7%D9%84%D8%BA%D9%84%D9%88%D9%83%D8%A7%D9%83%D9%88%D9%86-_1" title="ببتيد شبيه بالغلوكاكون- 1 – Arabic" lang="ar" hreflang="ar" data-title="ببتيد شبيه بالغلوكاكون- 1" data-language-autonym="العربية" data-language-local-name="Arabic" class="interlanguage-link-target"><span>العربية</span></a></li><li class="interlanguage-link interwiki-ca mw-list-item"><a href="https://ca.wikipedia.org/wiki/P%C3%A8ptid_similar_al_glucag%C3%B3_tipus_1" title="Pèptid similar al glucagó tipus 1 – Catalan" lang="ca" hreflang="ca" data-title="Pèptid similar al glucagó tipus 1" data-language-autonym="Català" data-language-local-name="Catalan" class="interlanguage-link-target"><span>Català</span></a></li><li class="interlanguage-link interwiki-de mw-list-item"><a href="https://de.wikipedia.org/wiki/Glucagon-like_Peptide_1" title="Glucagon-like Peptide 1 – German" lang="de" hreflang="de" data-title="Glucagon-like Peptide 1" data-language-autonym="Deutsch" data-language-local-name="German" class="interlanguage-link-target"><span>Deutsch</span></a></li><li class="interlanguage-link interwiki-es mw-list-item"><a href="https://es.wikipedia.org/wiki/P%C3%A9ptido_similar_al_glucag%C3%B3n_tipo_1" title="Péptido similar al glucagón tipo 1 – Spanish" lang="es" hreflang="es" data-title="Péptido similar al glucagón tipo 1" data-language-autonym="Español" data-language-local-name="Spanish" class="interlanguage-link-target"><span>Español</span></a></li><li class="interlanguage-link interwiki-fa mw-list-item"><a href="https://fa.wikipedia.org/wiki/%D9%BE%D9%BE%D8%AA%DB%8C%D8%AF_%D8%B4%D8%A8%D9%87%E2%80%8C%DA%AF%D9%84%D9%88%DA%A9%D8%A7%DA%AF%D9%88%D9%86_%DB%B1" title="پپتید شبه‌گلوکاگون ۱ – Persian" lang="fa" hreflang="fa" data-title="پپتید شبه‌گلوکاگون ۱" data-language-autonym="فارسی" data-language-local-name="Persian" class="interlanguage-link-target"><span>فارسی</span></a></li><li class="interlanguage-link interwiki-fr mw-list-item"><a href="https://fr.wikipedia.org/wiki/Glucagon-like_peptide-1" title="Glucagon-like peptide-1 – French" lang="fr" hreflang="fr" data-title="Glucagon-like peptide-1" data-language-autonym="Français" data-language-local-name="French" class="interlanguage-link-target"><span>Français</span></a></li><li class="interlanguage-link interwiki-gl mw-list-item"><a href="https://gl.wikipedia.org/wiki/P%C3%A9ptido_similar_ao_glicag%C3%B3n_1" title="Péptido similar ao glicagón 1 – Galician" lang="gl" hreflang="gl" data-title="Péptido similar ao glicagón 1" data-language-autonym="Galego" data-language-local-name="Galician" class="interlanguage-link-target"><span>Galego</span></a></li><li class="interlanguage-link interwiki-hy mw-list-item"><a href="https://hy.wikipedia.org/wiki/%D4%B3%D5%AC%D5%B5%D5%B8%D6%82%D5%AF%D5%A1%D5%A3%D5%B8%D5%B6%D5%A1%D5%B6%D5%B4%D5%A1%D5%B6_%D5%BA%D5%A5%D5%BA%D5%BF%D5%AB%D5%A4-1" title="Գլյուկագոնանման պեպտիդ-1 – Armenian" lang="hy" hreflang="hy" data-title="Գլյուկագոնանման պեպտիդ-1" data-language-autonym="Հայերեն" data-language-local-name="Armenian" class="interlanguage-link-target"><span>Հայերեն</span></a></li><li class="interlanguage-link interwiki-id mw-list-item"><a href="https://id.wikipedia.org/wiki/GLP-1" title="GLP-1 – Indonesian" lang="id" hreflang="id" data-title="GLP-1" data-language-autonym="Bahasa Indonesia" data-language-local-name="Indonesian" class="interlanguage-link-target"><span>Bahasa Indonesia</span></a></li><li class="interlanguage-link interwiki-mk mw-list-item"><a href="https://mk.wikipedia.org/wiki/%D0%93%D0%BB%D1%83%D0%BA%D0%B0%D0%B3%D0%BE%D0%BD%D0%BE%D0%BB%D0%B8%D0%BA_%D0%BF%D0%B5%D0%BF%D1%82%D0%B8%D0%B4-1" title="Глукагонолик пептид-1 – Macedonian" lang="mk" hreflang="mk" data-title="Глукагонолик пептид-1" data-language-autonym="Македонски" data-language-local-name="Macedonian" class="interlanguage-link-target"><span>Македонски</span></a></li><li class="interlanguage-link interwiki-nl mw-list-item"><a href="https://nl.wikipedia.org/wiki/GLP-1" title="GLP-1 – Dutch" lang="nl" hreflang="nl" data-title="GLP-1" data-language-autonym="Nederlands" data-language-local-name="Dutch" class="interlanguage-link-target"><span>Nederlands</span></a></li><li class="interlanguage-link interwiki-ja mw-list-item"><a href="https://ja.wikipedia.org/wiki/GLP-1" title="GLP-1 – Japanese" lang="ja" hreflang="ja" data-title="GLP-1" data-language-autonym="日本語" data-language-local-name="Japanese" class="interlanguage-link-target"><span>日本語</span></a></li><li class="interlanguage-link interwiki-pl mw-list-item"><a href="https://pl.wikipedia.org/wiki/Peptyd_glukagonopodobny_1" title="Peptyd glukagonopodobny 1 – Polish" lang="pl" hreflang="pl" data-title="Peptyd glukagonopodobny 1" data-language-autonym="Polski" data-language-local-name="Polish" class="interlanguage-link-target"><span>Polski</span></a></li><li class="interlanguage-link interwiki-pt mw-list-item"><a href="https://pt.wikipedia.org/wiki/Pept%C3%ADdeo_semelhante_a_glucagon_1" title="Peptídeo semelhante a glucagon 1 – Portuguese" lang="pt" hreflang="pt" data-title="Peptídeo semelhante a glucagon 1" data-language-autonym="Português" data-language-local-name="Portuguese" class="interlanguage-link-target"><span>Português</span></a></li><li class="interlanguage-link interwiki-ru mw-list-item"><a href="https://ru.wikipedia.org/wiki/%D0%93%D0%BB%D1%8E%D0%BA%D0%B0%D0%B3%D0%BE%D0%BD%D0%BE%D0%BF%D0%BE%D0%B4%D0%BE%D0%B1%D0%BD%D1%8B%D0%B9_%D0%BF%D0%B5%D0%BF%D1%82%D0%B8%D0%B4-1" title="Глюкагоноподобный пептид-1 – Russian" lang="ru" hreflang="ru" data-title="Глюкагоноподобный пептид-1" data-language-autonym="Русский" data-language-local-name="Russian" class="interlanguage-link-target"><span>Русский</span></a></li><li class="interlanguage-link interwiki-sr mw-list-item"><a href="https://sr.wikipedia.org/wiki/Glukagonu_sli%C4%8Dan_peptid-1" title="Glukagonu sličan peptid-1 – Serbian" lang="sr" hreflang="sr" data-title="Glukagonu sličan peptid-1" data-language-autonym="Српски / srpski" data-language-local-name="Serbian" class="interlanguage-link-target"><span>Српски / srpski</span></a></li><li class="interlanguage-link interwiki-sh mw-list-item"><a href="https://sh.wikipedia.org/wiki/Glukagonu_sli%C4%8Dan_peptid-1" title="Glukagonu sličan peptid-1 – Serbo-Croatian" lang="sh" hreflang="sh" data-title="Glukagonu sličan peptid-1" data-language-autonym="Srpskohrvatski / српскохрватски" data-language-local-name="Serbo-Croatian" class="interlanguage-link-target"><span>Srpskohrvatski / српскохрватски</span></a></li><li class="interlanguage-link interwiki-fi mw-list-item"><a href="https://fi.wikipedia.org/wiki/GLP-1" title="GLP-1 – Finnish" lang="fi" hreflang="fi" data-title="GLP-1" data-language-autonym="Suomi" data-language-local-name="Finnish" class="interlanguage-link-target"><span>Suomi</span></a></li><li class="interlanguage-link interwiki-vi mw-list-item"><a href="https://vi.wikipedia.org/wiki/Peptide_gi%E1%BB%91ng_Glucagon-1" title="Peptide giống Glucagon-1 – Vietnamese" lang="vi" hreflang="vi" data-title="Peptide giống Glucagon-1" data-language-autonym="Tiếng Việt" 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data-unpinned-container-id="vector-appearance-unpinned-container" > <div class="vector-pinnable-header-label">Appearance</div> <button class="vector-pinnable-header-toggle-button vector-pinnable-header-pin-button" data-event-name="pinnable-header.vector-appearance.pin">move to sidebar</button> <button class="vector-pinnable-header-toggle-button vector-pinnable-header-unpin-button" data-event-name="pinnable-header.vector-appearance.unpin">hide</button> </div> </div> </div> </nav> </div> </div> <div id="bodyContent" class="vector-body" aria-labelledby="firstHeading" data-mw-ve-target-container> <div class="vector-body-before-content"> <div class="mw-indicators"> </div> <div id="siteSub" class="noprint">From Wikipedia, the free encyclopedia</div> </div> <div id="contentSub"><div id="mw-content-subtitle"></div></div> <div id="mw-content-text" class="mw-body-content"><div class="mw-content-ltr mw-parser-output" lang="en" dir="ltr"><div class="shortdescription nomobile noexcerpt noprint searchaux" style="display:none">Gastrointestinal peptide hormone involved in glucose homeostasis</div> <p class="mw-empty-elt"> </p> <figure class="mw-halign-right" typeof="mw:File/Thumb"><a href="/wiki/File:Incretins_and_DPP_4_inhibitors.svg" class="mw-file-description"><img src="//upload.wikimedia.org/wikipedia/commons/thumb/6/64/Incretins_and_DPP_4_inhibitors.svg/350px-Incretins_and_DPP_4_inhibitors.svg.png" decoding="async" width="350" height="213" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/6/64/Incretins_and_DPP_4_inhibitors.svg/525px-Incretins_and_DPP_4_inhibitors.svg.png 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/6/64/Incretins_and_DPP_4_inhibitors.svg/700px-Incretins_and_DPP_4_inhibitors.svg.png 2x" data-file-width="522" data-file-height="317" /></a><figcaption>GLP-1 and diabetes</figcaption></figure> <p><b>Glucagon-like peptide-1</b> (<b>GLP-1</b>) is a 30- or 31-amino-acid-long <a href="/wiki/Peptide_hormone" title="Peptide hormone">peptide hormone</a> deriving from the tissue-specific posttranslational processing of the <a href="/wiki/Proglucagon" title="Proglucagon">proglucagon</a> peptide. It is produced and secreted by intestinal <a href="/wiki/Enteroendocrine_cell" title="Enteroendocrine cell">enteroendocrine L-cells</a> and certain neurons within the <a href="/wiki/Solitary_nucleus" title="Solitary nucleus">nucleus of the solitary tract</a> in the brainstem upon food consumption. The initial product GLP-1 (1–37) is susceptible to <a href="/wiki/Amidation" class="mw-redirect" title="Amidation">amidation</a> and <a href="/wiki/Proteolytic_cleavage" class="mw-redirect" title="Proteolytic cleavage">proteolytic cleavage</a>, which gives rise to the two truncated and equipotent biologically active forms, GLP-1 (7–36) amide and GLP-1 (7–37). Active GLP-1 <a href="/wiki/Protein_secondary_structure" title="Protein secondary structure">protein secondary structure</a> includes two <a href="/wiki/%CE%91-helices" class="mw-redirect" title="Α-helices">α-helices</a> from amino acid position 13–20 and 24–35 separated by a linker region. </p><p>Alongside <a href="/wiki/Glucose-dependent_insulinotropic_peptide" class="mw-redirect" title="Glucose-dependent insulinotropic peptide">glucose-dependent insulinotropic peptide</a> (GIP), GLP-1 is an <a href="/wiki/Incretin" title="Incretin">incretin</a>; thus, it has the ability to decrease <a href="/wiki/Blood_sugar_levels" class="mw-redirect" title="Blood sugar levels">blood sugar levels</a> in a glucose-dependent manner by enhancing the <a href="/wiki/Secretion" title="Secretion">secretion</a> of <a href="/wiki/Insulin" title="Insulin">insulin</a>. Beside the insulinotropic effects, GLP-1 has been associated with numerous regulatory and protective effects. Unlike GIP, the action of GLP-1 is preserved in patients with <a href="/wiki/Type_2_diabetes" title="Type 2 diabetes">type 2 diabetes</a>. <a href="/wiki/Glucagon-like_peptide-1_receptor_agonist" class="mw-redirect" title="Glucagon-like peptide-1 receptor agonist">Glucagon-like peptide-1 receptor agonists</a> gained approval as drugs to treat diabetes and obesity starting in the 2000s. </p><p>Endogenous GLP-1 is rapidly degraded primarily by <a href="/wiki/Dipeptidyl_peptidase-4" title="Dipeptidyl peptidase-4">dipeptidyl peptidase-4</a> (DPP-4), as well as neutral endopeptidase 24.11 (NEP 24.11) and <a href="/wiki/Renal_clearance" class="mw-redirect" title="Renal clearance">renal clearance</a>, resulting in a <a href="/wiki/Half-life" title="Half-life">half-life</a> of approximately 2 minutes. Consequently, only 10–15 % of GLP-1 reaches circulation intact, leading to fasting plasma levels of only 0–15 pmol/L. To overcome this, <a href="/wiki/GLP-1_receptor_agonist" title="GLP-1 receptor agonist">GLP-1 receptor agonists</a> and <a href="/wiki/DPP-4_inhibitors" class="mw-redirect" title="DPP-4 inhibitors">DPP-4 inhibitors</a> have been developed to increase GLP-1 activity. As opposed to common treatment agents such as <a href="/wiki/Insulin" title="Insulin">insulin</a> and <a href="/wiki/Sulphonylurea" class="mw-redirect" title="Sulphonylurea">sulphonylurea</a>, GLP-1-based treatment has been associated with <a href="/wiki/Weight_loss" title="Weight loss">weight loss</a> and a lower risk of <a href="/wiki/Hypoglycemia" title="Hypoglycemia">hypoglycemia</a>, two important considerations for patients with type 2 diabetes. </p> <meta property="mw:PageProp/toc" /> <div class="mw-heading mw-heading2"><h2 id="Gene_expression">Gene expression</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Glucagon-like_peptide-1&action=edit&section=1" title="Edit section: Gene expression"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>The proglucagon gene is expressed in several organs including the <a href="/wiki/Pancreas" title="Pancreas">pancreas</a> (<a href="/wiki/%CE%91-cell" class="mw-redirect" title="Α-cell">α-cells</a> of the <a href="/wiki/Islets_of_Langerhans" class="mw-redirect" title="Islets of Langerhans">islets of Langerhans</a>), gut (intestinal enteroendocrine L-cells) and <a href="/wiki/Brain" title="Brain">brain</a> (caudal <a href="/wiki/Brainstem" title="Brainstem">brainstem</a> and <a href="/wiki/Hypothalamus" title="Hypothalamus">hypothalamus</a>). Pancreatic proglucagon gene expression is promoted upon fasting and hypoglycaemia induction and inhibited by insulin. Conversely, intestinal proglucagon gene expression is reduced during fasting and stimulated upon food consumption. In mammals, the transcription gives rise to identical <a href="/wiki/MRNA" class="mw-redirect" title="MRNA">mRNA</a> in all three cell types, which is further translated to the 180 amino acid precursor called <a href="/wiki/Proglucagon" title="Proglucagon">proglucagon</a>. However, as a result of tissue-specific posttranslational processing mechanisms, different peptides are produced in the different cells.<sup id="cite_ref-marathe_1-0" class="reference"><a href="#cite_note-marathe-1"><span class="cite-bracket">[</span>1<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-drucker_2-0" class="reference"><a href="#cite_note-drucker-2"><span class="cite-bracket">[</span>2<span class="cite-bracket">]</span></a></sup> </p><p>In the <a href="/wiki/Pancreas" title="Pancreas">pancreas</a> (<a href="/wiki/%CE%91-cell" class="mw-redirect" title="Α-cell">α-cells</a> of the <a href="/wiki/Islets_of_Langerhans" class="mw-redirect" title="Islets of Langerhans">islets of Langerhans</a>), <a href="/wiki/Proglucagon" title="Proglucagon">proglucagon</a> is cleaved by <a href="/wiki/Prohormone_convertase" class="mw-redirect" title="Prohormone convertase">prohormone convertase</a> (PC) 2 producing glicentin-related pancreatic peptide (GRPP), <a href="/wiki/Glucagon" title="Glucagon">glucagon</a>, intervening peptide-1 (IP-1) and major proglucagon fragment (MPGF).<sup id="cite_ref-jjholst_3-0" class="reference"><a href="#cite_note-jjholst-3"><span class="cite-bracket">[</span>3<span class="cite-bracket">]</span></a></sup> </p><p>In the gut and brain, <a href="/wiki/Proglucagon" title="Proglucagon">proglucagon</a> is catalysed by PC 1/3 giving rise to glicentin, which may be further processed to GRPP and <a href="/wiki/Oxyntomodulin" title="Oxyntomodulin">oxyntomodulin</a>, GLP-1, intervening peptide-2 (IP-2) and <a href="/wiki/Glucagon-like_peptide-2" title="Glucagon-like peptide-2">glucagon-like peptide-2</a> (<a href="/wiki/GLP-2" class="mw-redirect" title="GLP-2">GLP-2</a>). Initially, GLP-1 was thought to correspond to proglucagon (72–108) suitable with the <a href="/wiki/N-terminal" class="mw-redirect" title="N-terminal">N-terminal</a> of the MPGF, but sequencing experiments of endogenous GLP-1 revealed a structure corresponding to proglucagon (78–107) from which two discoveries were found. Firstly, the full-length GLP-1 (1–37) was found to be catalysed by <a href="/wiki/Endopeptidase" title="Endopeptidase">endopeptidase</a> to the biologically active GLP-1 (7–37). Secondly, the <a href="/wiki/Glycine" title="Glycine">glycine</a> corresponding to proglucagon(108) was found to serve as a substrate for <a href="/wiki/Amidation" class="mw-redirect" title="Amidation">amidation</a> of the <a href="/wiki/C-terminal" class="mw-redirect" title="C-terminal">C-terminal</a> <a href="/wiki/Arginine" title="Arginine">arginine</a> resulting in the equally potent GLP-1 (7–36) amide. In humans, almost all (>80%) secreted GLP-1 is amidated, whereas a considerable part remains GLP-1 (7–37) in other species.<sup id="cite_ref-jjholst_3-1" class="reference"><a href="#cite_note-jjholst-3"><span class="cite-bracket">[</span>3<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-4" class="reference"><a href="#cite_note-4"><span class="cite-bracket">[</span>4<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading2"><h2 id="Secretion">Secretion</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Glucagon-like_peptide-1&action=edit&section=2" title="Edit section: Secretion"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>GLP-1 is packaged in secretory granules and secreted into the <a href="/wiki/Hepatic_portal_system" title="Hepatic portal system">hepatic portal system</a> by the intestinal L-cells located primarily in the distal <a href="/wiki/Ileum" title="Ileum">ileum</a> and colon, but also found in the <a href="/wiki/Jejunum" title="Jejunum">jejunum</a> and <a href="/wiki/Duodenum" title="Duodenum">duodenum</a>. The L-cells are open-type triangular <a href="/wiki/Epithelial_cells" class="mw-redirect" title="Epithelial cells">epithelial cells</a> directly in contact with the <a href="/wiki/Lumen_(anatomy)" title="Lumen (anatomy)">lumen</a> and neuro-vascular tissue and are accordingly stimulated by various <a href="/wiki/Nutrient" title="Nutrient">nutrient</a>, <a href="/wiki/Neural" class="mw-redirect" title="Neural">neural</a> and <a href="/wiki/Endocrine" class="mw-redirect" title="Endocrine">endocrine</a> factors.<sup id="cite_ref-drucker_2-1" class="reference"><a href="#cite_note-drucker-2"><span class="cite-bracket">[</span>2<span class="cite-bracket">]</span></a></sup> </p><p>GLP-1 is released in a <a href="/wiki/Phase_(pharmacology)" class="mw-redirect" title="Phase (pharmacology)">biphasic</a> pattern with an early phase after 10–15 minutes followed by a longer second phase after 30–60 minutes upon meal ingestion. As the majority of L-cells are located in the distal <a href="/wiki/Ileum" title="Ileum">ileum</a> and colon, the early phase is likely explained by neural signalling, gut peptides or <a href="/wiki/Neurotransmitters" class="mw-redirect" title="Neurotransmitters">neurotransmitters</a>. Other evidence suggest that the amount of L-cells located in the proximal <a href="/wiki/Jejunum" title="Jejunum">jejunum</a> is sufficient to account for the early phase secretion through direct contact with luminal nutrients. Less controversially, the second phase is likely caused by direct stimulation of L-cells by digested <a href="/wiki/Nutrients" class="mw-redirect" title="Nutrients">nutrients</a>. The rate of <a href="/wiki/Gastric_emptying" class="mw-redirect" title="Gastric emptying">gastric emptying</a> is therefore an important aspect to consider, as it regulates the entry of nutrients into the <a href="/wiki/Small_intestines" class="mw-redirect" title="Small intestines">small intestines</a> where the direct stimulation occurs. One of the actions of GLP-1 is to inhibit <a href="/wiki/Gastric_emptying" class="mw-redirect" title="Gastric emptying">gastric emptying</a>, thus slowing down its own <a href="/wiki/Secretion" title="Secretion">secretion</a> upon <a href="/wiki/Postprandial" class="mw-redirect" title="Postprandial">postprandial</a> activation.<sup id="cite_ref-marathe_1-1" class="reference"><a href="#cite_note-marathe-1"><span class="cite-bracket">[</span>1<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-drucker_2-2" class="reference"><a href="#cite_note-drucker-2"><span class="cite-bracket">[</span>2<span class="cite-bracket">]</span></a></sup> </p><p>Fasting plasma concentration of biologically active GLP-1 range between 0 and 15 pmol/L in humans and is increased 2- to 3-fold upon food consumption depending on meal size and nutrient composition. Individual nutrients, such as <a href="/wiki/Fatty_acids" class="mw-redirect" title="Fatty acids">fatty acids</a>, <a href="/wiki/Essential_amino_acids" class="mw-redirect" title="Essential amino acids">essential amino acids</a> and <a href="/wiki/Dietary_fibre" class="mw-redirect" title="Dietary fibre">dietary fibre</a> have also shown to stimulate GLP-1 secretion. </p><p><a href="/wiki/Sugars" class="mw-redirect" title="Sugars">Sugars</a> have been associated with various <a href="/wiki/Signalling_pathways" class="mw-redirect" title="Signalling pathways">signalling pathways</a>, which initiate <a href="/wiki/Depolarisation" class="mw-redirect" title="Depolarisation">depolarisation</a> of the L-cell membrane causing an elevated concentration of <a href="/wiki/Cytosolic" class="mw-redirect" title="Cytosolic">cytosolic</a> Ca<sup>2+</sup> which in turn induce GLP-1 secretion. <a href="/wiki/Fatty_acids" class="mw-redirect" title="Fatty acids">Fatty acids</a> have been associated with the mobilisation of <a href="/wiki/Intracellular" class="mw-redirect" title="Intracellular">intracellular</a> Ca<sup>2+</sup> stores and subsequently release of Ca<sup>2+</sup> into the <a href="/wiki/Cytosol" title="Cytosol">cytosol</a>. The mechanisms of protein-triggered GLP-1 secretion are less clear, but the <a href="/wiki/Amino_acid" title="Amino acid">amino acid</a> proportion and composition appear important to the stimulatory effect.<sup id="cite_ref-5" class="reference"><a href="#cite_note-5"><span class="cite-bracket">[</span>5<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading2"><h2 id="Degradation">Degradation</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Glucagon-like_peptide-1&action=edit&section=3" title="Edit section: Degradation"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>Once secreted, GLP-1 is extremely susceptible to the catalytic activity of the proteolytic enzyme <a href="/wiki/Dipeptidyl_peptidase-4" title="Dipeptidyl peptidase-4">dipeptidyl peptidase-4</a> (<a href="/wiki/DPP-4" class="mw-redirect" title="DPP-4">DPP-4</a>). Specifically, <a href="/wiki/DPP-4" class="mw-redirect" title="DPP-4">DPP-4</a> cleaves the <a href="/wiki/Peptide_bond" title="Peptide bond">peptide bond</a> between <a href="/wiki/Alanine" title="Alanine">Ala</a><sup>8</sup>-<a href="/wiki/Glutamic_acid" title="Glutamic acid">Glu</a><sup>9</sup> resulting in the abundant GLP-1 (9–36) amide constituting 60–80 % of total GLP-1 in circulation. <a href="/wiki/DPP-4" class="mw-redirect" title="DPP-4">DPP-4</a> is widely expressed in multiple tissues and cell types and exists in both a membrane-anchored and soluble circulating form. Notably, <a href="/wiki/DPP-4" class="mw-redirect" title="DPP-4">DPP-4</a> is expressed on the surface of <a href="/wiki/Endothelial_cells" class="mw-redirect" title="Endothelial cells">endothelial cells</a>, including those located directly adjacent to GLP-1 secretion sites.<sup id="cite_ref-drucker_2-3" class="reference"><a href="#cite_note-drucker-2"><span class="cite-bracket">[</span>2<span class="cite-bracket">]</span></a></sup> Consequently, less than 25% of secreted GLP-1 is estimated to leave the gut intact. Additionally, presumably due to the high concentration of <a href="/wiki/DPP-4" class="mw-redirect" title="DPP-4">DPP-4</a> found on <a href="/wiki/Hepatocytes" class="mw-redirect" title="Hepatocytes">hepatocytes</a>, 40–50% of the remaining active GLP-1 is degraded across the <a href="/wiki/Liver" title="Liver">liver</a>. Thus, due to the activity of <a href="/wiki/DPP-4" class="mw-redirect" title="DPP-4">DPP-4</a> only 10–15 % of secreted GLP-1 reaches circulation intact.<sup id="cite_ref-jjholst_3-2" class="reference"><a href="#cite_note-jjholst-3"><span class="cite-bracket">[</span>3<span class="cite-bracket">]</span></a></sup> </p><p><a href="/wiki/Neutral_endopeptidase" class="mw-redirect" title="Neutral endopeptidase">Neutral endopeptidase</a> 24.11 (NEP 24.11) is a membrane-bound zinc metallopeptidase widely expressed in several tissues, but found in particularly high concentrations in the <a href="/wiki/Kidneys" class="mw-redirect" title="Kidneys">kidneys</a>, which is also identified accountable for the rapid degradation of GLP-1. It primarily cleaves peptides at the <a href="/wiki/N-terminal" class="mw-redirect" title="N-terminal">N-terminal</a> side of <a href="/wiki/Aromatic_amino_acids" class="mw-redirect" title="Aromatic amino acids">aromatic amino acids</a> or <a href="/wiki/Hydrophobic" class="mw-redirect" title="Hydrophobic">hydrophobic</a> <a href="/wiki/Amino_acids" class="mw-redirect" title="Amino acids">amino acids</a> and is estimated to contribute by up to 50% of the GLP-1 degradation. However, the activity only becomes apparent once the degradation of <a href="/wiki/DPP-4" class="mw-redirect" title="DPP-4">DPP-4</a> has been prevented, as the majority of GLP-1 reaching the <a href="/wiki/Kidneys" class="mw-redirect" title="Kidneys">kidneys</a> have already been processed by <a href="/wiki/DPP-4" class="mw-redirect" title="DPP-4">DPP-4</a>. Similarly, <a href="/wiki/Renal_clearance" class="mw-redirect" title="Renal clearance">renal clearance</a> appear more significant for the elimination of already inactivated GLP-1.<sup id="cite_ref-6" class="reference"><a href="#cite_note-6"><span class="cite-bracket">[</span>6<span class="cite-bracket">]</span></a></sup> </p><p>The resulting <a href="/wiki/Half-life" title="Half-life">half-life</a> of active GLP-1 is approximately 2 minutes, which is however sufficient to activate <a href="/wiki/GLP-1_receptor" class="mw-redirect" title="GLP-1 receptor">GLP-1 receptors</a>. </p> <div class="mw-heading mw-heading2"><h2 id="Physiological_functions">Physiological functions</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Glucagon-like_peptide-1&action=edit&section=4" title="Edit section: Physiological functions"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <figure class="mw-default-size mw-halign-right" typeof="mw:File/Thumb"><a href="/wiki/File:FunctionsOfGLP-1.png" class="mw-file-description"><img src="//upload.wikimedia.org/wikipedia/en/thumb/7/7b/FunctionsOfGLP-1.png/220px-FunctionsOfGLP-1.png" decoding="async" width="220" height="174" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/en/thumb/7/7b/FunctionsOfGLP-1.png/330px-FunctionsOfGLP-1.png 1.5x, //upload.wikimedia.org/wikipedia/en/thumb/7/7b/FunctionsOfGLP-1.png/440px-FunctionsOfGLP-1.png 2x" data-file-width="3452" data-file-height="2732" /></a><figcaption>Functions of GLP-1</figcaption></figure> <p>GLP-1 possesses several physiological properties making it (and its <a href="/wiki/Functional_analog_(chemistry)" title="Functional analog (chemistry)">functional analogs</a>) a subject of intensive investigation as a potential treatment of <a href="/wiki/Diabetes_mellitus" class="mw-redirect" title="Diabetes mellitus">diabetes mellitus</a>, as these actions induce long-term improvements along with the immediate effects.<sup class="noprint Inline-Template" style="white-space:nowrap;">[<i><a href="/wiki/Wikipedia:Verifiability" title="Wikipedia:Verifiability"><span title="Quotation needed from source to verify. (June 2017)">need quotation to verify</span></a></i>]</sup><sup id="cite_ref-7" class="reference"><a href="#cite_note-7"><span class="cite-bracket">[</span>7<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-8" class="reference"><a href="#cite_note-8"><span class="cite-bracket">[</span>8<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-9" class="reference"><a href="#cite_note-9"><span class="cite-bracket">[</span>9<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-10" class="reference"><a href="#cite_note-10"><span class="cite-bracket">[</span>10<span class="cite-bracket">]</span></a></sup> Although reduced GLP-1 secretion has previously been associated with attenuated incretin effect in patients with <a href="/wiki/Type_2_diabetes" title="Type 2 diabetes">type 2 diabetes</a>, it is now granted that GLP-1 secretion in patients with type 2 diabetes does not differ from healthy subjects.<sup id="cite_ref-11" class="reference"><a href="#cite_note-11"><span class="cite-bracket">[</span>11<span class="cite-bracket">]</span></a></sup> </p><p>The most noteworthy effect of GLP-1 is its ability to promote insulin secretion in a glucose-dependent manner. As GLP-1 binds to <a href="/wiki/GLP-1_receptor" class="mw-redirect" title="GLP-1 receptor">GLP-1 receptors</a> expressed on the <a href="/wiki/Beta_cell" title="Beta cell">pancreatic β cells</a>, the receptors couple to <a href="/wiki/Heterotrimeric_G_protein" title="Heterotrimeric G protein">G-protein</a> subunits and activate <a href="/wiki/Adenylate_cyclase" class="mw-redirect" title="Adenylate cyclase">adenylate cyclase</a> that increases the production of <a href="/wiki/Cyclic_adenosine_monophosphate" title="Cyclic adenosine monophosphate">cAMP</a> from <a href="/wiki/Adenosine_triphosphate" title="Adenosine triphosphate">ATP</a>.<sup id="cite_ref-jjholst_3-3" class="reference"><a href="#cite_note-jjholst-3"><span class="cite-bracket">[</span>3<span class="cite-bracket">]</span></a></sup> Subsequently, activation of secondary pathways, including PKA and <a href="/wiki/RAPGEF4" title="RAPGEF4">Epac2</a>, alters the ion channel activity causing elevated levels of cytosolic Ca<sup>2+</sup> that enhances exocytosis of insulin-containing granules. During the process, influx of glucose ensures sufficient ATP to sustain the stimulatory effect.<sup id="cite_ref-jjholst_3-4" class="reference"><a href="#cite_note-jjholst-3"><span class="cite-bracket">[</span>3<span class="cite-bracket">]</span></a></sup> </p><p>Additionally, GLP-1 ensures the β cell insulin stores are replenished to prevent exhaustion during secretion by promoting insulin gene transcription, <a href="/wiki/MRNA" class="mw-redirect" title="MRNA">mRNA</a> stability and biosynthesis.<sup id="cite_ref-drucker_2-4" class="reference"><a href="#cite_note-drucker-2"><span class="cite-bracket">[</span>2<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-rondas_12-0" class="reference"><a href="#cite_note-rondas-12"><span class="cite-bracket">[</span>12<span class="cite-bracket">]</span></a></sup> GLP-1 evidently also increases<sup id="cite_ref-Rachmany_1621–1636_13-0" class="reference"><a href="#cite_note-Rachmany_1621–1636-13"><span class="cite-bracket">[</span>13<span class="cite-bracket">]</span></a></sup> β cell mass by promoting proliferation and neogenesis while inhibiting <a href="/wiki/Apoptosis" title="Apoptosis">apoptosis</a>. As both type 1 and 2 diabetes are associated with reduction of functional β cells, this effect is highly interesting regarding diabetes treatment.<sup id="cite_ref-rondas_12-1" class="reference"><a href="#cite_note-rondas-12"><span class="cite-bracket">[</span>12<span class="cite-bracket">]</span></a></sup> Considered almost as important as the effect of enhancing insulin secretion, GLP-1 has been shown to inhibit glucagon secretion at glucose levels above fasting levels. Critically, this does not affect the glucagon response to <a href="/wiki/Hypoglycemia" title="Hypoglycemia">hypoglycemia</a> as this effect is also glucose-dependent. The inhibitory effect is presumably mediated indirectly through <a href="/wiki/Somatostatin" title="Somatostatin">somatostatin</a> secretion, but a direct effect cannot be completely excluded.<sup id="cite_ref-gautier_14-0" class="reference"><a href="#cite_note-gautier-14"><span class="cite-bracket">[</span>14<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-seino_15-0" class="reference"><a href="#cite_note-seino-15"><span class="cite-bracket">[</span>15<span class="cite-bracket">]</span></a></sup> </p><p>In the brain, GLP-1 receptor activation has been linked with neurotrophic effects including <a href="/wiki/Neurogenesis" title="Neurogenesis">neurogenesis</a><sup id="cite_ref-16" class="reference"><a href="#cite_note-16"><span class="cite-bracket">[</span>16<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-Bertilsson_326–338_17-0" class="reference"><a href="#cite_note-Bertilsson_326–338-17"><span class="cite-bracket">[</span>17<span class="cite-bracket">]</span></a></sup> and <a href="/wiki/Neuroprotection" title="Neuroprotection">neuroprotective</a> effects including reduced necrotic<sup id="cite_ref-DellaValle_721–732_18-0" class="reference"><a href="#cite_note-DellaValle_721–732-18"><span class="cite-bracket">[</span>18<span class="cite-bracket">]</span></a></sup> and apoptotic<sup id="cite_ref-19" class="reference"><a href="#cite_note-19"><span class="cite-bracket">[</span>19<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-DellaValle_721–732_18-1" class="reference"><a href="#cite_note-DellaValle_721–732-18"><span class="cite-bracket">[</span>18<span class="cite-bracket">]</span></a></sup> signaling, <a href="/wiki/Cell_death" title="Cell death">cell death</a>,<sup id="cite_ref-20" class="reference"><a href="#cite_note-20"><span class="cite-bracket">[</span>20<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-21" class="reference"><a href="#cite_note-21"><span class="cite-bracket">[</span>21<span class="cite-bracket">]</span></a></sup> and dysfunctions.<sup id="cite_ref-22" class="reference"><a href="#cite_note-22"><span class="cite-bracket">[</span>22<span class="cite-bracket">]</span></a></sup> In the diseased brain, GLP-1 receptor agonist treatment is associated with protection against a range of experimental disease models such as <a href="/wiki/Parkinson%27s_disease" title="Parkinson's disease">Parkinson's disease</a>,<sup id="cite_ref-Li_1285–1290_23-0" class="reference"><a href="#cite_note-Li_1285–1290-23"><span class="cite-bracket">[</span>23<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-Bertilsson_326–338_17-1" class="reference"><a href="#cite_note-Bertilsson_326–338-17"><span class="cite-bracket">[</span>17<span class="cite-bracket">]</span></a></sup> <a href="/wiki/Alzheimer%27s_disease" title="Alzheimer's disease">Alzheimer's disease</a>,<sup id="cite_ref-24" class="reference"><a href="#cite_note-24"><span class="cite-bracket">[</span>24<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-25" class="reference"><a href="#cite_note-25"><span class="cite-bracket">[</span>25<span class="cite-bracket">]</span></a></sup> stroke,<sup id="cite_ref-Li_1285–1290_23-1" class="reference"><a href="#cite_note-Li_1285–1290-23"><span class="cite-bracket">[</span>23<span class="cite-bracket">]</span></a></sup> <a href="/wiki/Traumatic_brain_injury" title="Traumatic brain injury">traumatic brain injury</a>,<sup id="cite_ref-Rachmany_1621–1636_13-1" class="reference"><a href="#cite_note-Rachmany_1621–1636-13"><span class="cite-bracket">[</span>13<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-DellaValle_721–732_18-2" class="reference"><a href="#cite_note-DellaValle_721–732-18"><span class="cite-bracket">[</span>18<span class="cite-bracket">]</span></a></sup> and <a href="/wiki/Multiple_sclerosis" title="Multiple sclerosis">multiple sclerosis</a>.<sup id="cite_ref-26" class="reference"><a href="#cite_note-26"><span class="cite-bracket">[</span>26<span class="cite-bracket">]</span></a></sup> In accordance with the expression of GLP-1 receptor on brainstem and hypothalamus, GLP-1 has been shown to promote satiety and thereby reduce food and water intake. Consequently, diabetic subjects treated with GLP-1 receptor agonists often experience weight loss as opposed to the weight gain commonly induced with other treatment agents.<sup id="cite_ref-drucker_2-5" class="reference"><a href="#cite_note-drucker-2"><span class="cite-bracket">[</span>2<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-seino_15-1" class="reference"><a href="#cite_note-seino-15"><span class="cite-bracket">[</span>15<span class="cite-bracket">]</span></a></sup> </p><p>In the stomach, GLP-1 inhibits gastric emptying, acid secretion and motility, which collectively decrease appetite. By decelerating gastric emptying GLP-1 reduces postprandial glucose excursion which is another attractive property regarding diabetes treatment. However, these gastrointestinal activities are also the reason why subjects treated with GLP-1-based agents occasionally experience <a href="/wiki/Nausea" title="Nausea">nausea</a>.<sup id="cite_ref-gautier_14-1" class="reference"><a href="#cite_note-gautier-14"><span class="cite-bracket">[</span>14<span class="cite-bracket">]</span></a></sup> </p><p>GLP-1 has also shown signs of carrying out protective and regulatory effects in numerous other tissues, including heart, tongue, adipose, muscles, bones, kidneys, liver and lungs. </p> <div class="mw-heading mw-heading2"><h2 id="Research_history">Research history</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Glucagon-like_peptide-1&action=edit&section=5" title="Edit section: Research history"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>In the early 1980s, Richard Goodman and P. Kay Lund were <a href="/wiki/Postdoctoral_researcher" title="Postdoctoral researcher">postdoctoral researchers</a> working in <a href="/wiki/Joel_Habener" title="Joel Habener">Joel Habener</a>'s laboratory at <a href="/wiki/Massachusetts_General_Hospital" title="Massachusetts General Hospital">Massachusetts General Hospital</a>.<sup id="cite_ref-Molteni_27-0" class="reference"><a href="#cite_note-Molteni-27"><span class="cite-bracket">[</span>27<span class="cite-bracket">]</span></a></sup> Starting in 1979, Goodman harvested DNA from <a href="/wiki/Lophius_americanus" title="Lophius americanus">American anglerfish</a> <a href="/wiki/Pancreatic_islets" title="Pancreatic islets">islet cells</a> and spliced the DNA into bacteria to find the gene for <a href="/wiki/Somatostatin" title="Somatostatin">somatostatin</a>, then Lund joined the Habener lab and used Goodman's bacteria to search for the gene for glucagon.<sup id="cite_ref-Molteni_27-1" class="reference"><a href="#cite_note-Molteni-27"><span class="cite-bracket">[</span>27<span class="cite-bracket">]</span></a></sup> In 1982, they published their discovery that the gene for proglucagon actually codes for three peptides: glucagon and two novel peptides.<sup id="cite_ref-Molteni_27-2" class="reference"><a href="#cite_note-Molteni-27"><span class="cite-bracket">[</span>27<span class="cite-bracket">]</span></a></sup> Those two novel peptides were later isolated, identified, and investigated by other researchers, and are now known as glucagon-like peptide-1 and glucagon-like peptide-2.<sup id="cite_ref-Molteni_27-3" class="reference"><a href="#cite_note-Molteni-27"><span class="cite-bracket">[</span>27<span class="cite-bracket">]</span></a></sup> </p><p>In the 1980s, <a href="/wiki/Svetlana_Mojsov" title="Svetlana Mojsov">Svetlana Mojsov</a> worked on the identification of GLP-1 at Mass General, where she was head of a peptide synthesis facility.<sup id="cite_ref-:0_28-0" class="reference"><a href="#cite_note-:0-28"><span class="cite-bracket">[</span>28<span class="cite-bracket">]</span></a></sup> To try to identify whether a specific fragment of GLP-q was an incretin, Mojsov created an incretin-antibody and developed ways to track its presence. She identified that a stretch of 31 amino acids in the GLP-1 was an incretin.<sup id="cite_ref-29" class="reference"><a href="#cite_note-29"><span class="cite-bracket">[</span>29<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-30" class="reference"><a href="#cite_note-30"><span class="cite-bracket">[</span>30<span class="cite-bracket">]</span></a></sup> Mojsov and her collaborators <a href="/wiki/Daniel_J._Drucker" title="Daniel J. Drucker">Daniel J. Drucker</a> and Habener showed that small quantities of lab-synthesized GLP-1 could trigger insulin.<sup id="cite_ref-31" class="reference"><a href="#cite_note-31"><span class="cite-bracket">[</span>31<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-32" class="reference"><a href="#cite_note-32"><span class="cite-bracket">[</span>32<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-33" class="reference"><a href="#cite_note-33"><span class="cite-bracket">[</span>33<span class="cite-bracket">]</span></a></sup> </p><p>Mojsov fought to have her name included in patents, with Mass General eventually agreeing to amend four patents to include her name. She received her one-third of drug royalties for one year.<sup id="cite_ref-:03_34-0" class="reference"><a href="#cite_note-:03-34"><span class="cite-bracket">[</span>34<span class="cite-bracket">]</span></a></sup> </p><p>The discovery of GLP-1's extremely short half-life meant that it was impossible to develop into a drug.<sup id="cite_ref-Winkler_35-0" class="reference"><a href="#cite_note-Winkler-35"><span class="cite-bracket">[</span>35<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-Dunaief_36-0" class="reference"><a href="#cite_note-Dunaief-36"><span class="cite-bracket">[</span>36<span class="cite-bracket">]</span></a></sup> This caused diabetes research to shift towards other therapeutic options such as targeting the GLP-1 receptor, which then led to the development of GLP-1 receptor agonists.<sup id="cite_ref-Winkler_35-1" class="reference"><a href="#cite_note-Winkler-35"><span class="cite-bracket">[</span>35<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-Dunaief_36-1" class="reference"><a href="#cite_note-Dunaief-36"><span class="cite-bracket">[</span>36<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading2"><h2 id="See_also">See also</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Glucagon-like_peptide-1&action=edit&section=6" title="Edit section: See also"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <ul><li><a href="/wiki/Glucagon" title="Glucagon">Glucagon</a></li> <li><a href="/wiki/Glucagon-like_peptide_1_receptor" class="mw-redirect" title="Glucagon-like peptide 1 receptor">Glucagon-like peptide 1 receptor</a></li> <li><a href="/wiki/Glucagon-like_peptide-2" title="Glucagon-like peptide-2">Glucagon-like peptide-2</a></li> <li><a href="/wiki/Type_2_diabetes" title="Type 2 diabetes">Type 2 diabetes</a></li> <li><a href="/wiki/GLP-1_receptor_agonist" title="GLP-1 receptor agonist">GLP-1 receptor agonists</a> : <a href="/wiki/Albiglutide" title="Albiglutide">albiglutide</a>, <a href="/wiki/Dulaglutide" title="Dulaglutide">dulaglutide</a>, <a href="/wiki/Exenatide" title="Exenatide">exenatide</a>, <a href="/wiki/Liraglutide" title="Liraglutide">liraglutide</a>, <a href="/wiki/Lixisenatide" title="Lixisenatide">lixisenatide</a>, <a href="/wiki/Tirzepatide" title="Tirzepatide">tirzepatide</a> and <a href="/wiki/Semaglutide" title="Semaglutide">semaglutide</a>, the latter of which is marketed under the brands Ozempic, Rybelsus and Wegovy.</li> <li><a href="/wiki/Dipeptidyl_peptidase-4" title="Dipeptidyl peptidase-4">Dipeptidyl peptidase-4</a></li> <li><a href="/wiki/Glucose-dependent_insulinotropic_peptide" class="mw-redirect" title="Glucose-dependent insulinotropic peptide">Glucose-dependent insulinotropic peptide</a></li></ul> <div class="mw-heading mw-heading2"><h2 id="References">References</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Glucagon-like_peptide-1&action=edit&section=7" title="Edit section: References"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <style data-mw-deduplicate="TemplateStyles:r1239543626">.mw-parser-output .reflist{margin-bottom:0.5em;list-style-type:decimal}@media screen{.mw-parser-output .reflist{font-size:90%}}.mw-parser-output .reflist .references{font-size:100%;margin-bottom:0;list-style-type:inherit}.mw-parser-output .reflist-columns-2{column-width:30em}.mw-parser-output .reflist-columns-3{column-width:25em}.mw-parser-output .reflist-columns{margin-top:0.3em}.mw-parser-output .reflist-columns ol{margin-top:0}.mw-parser-output .reflist-columns li{page-break-inside:avoid;break-inside:avoid-column}.mw-parser-output .reflist-upper-alpha{list-style-type:upper-alpha}.mw-parser-output .reflist-upper-roman{list-style-type:upper-roman}.mw-parser-output .reflist-lower-alpha{list-style-type:lower-alpha}.mw-parser-output .reflist-lower-greek{list-style-type:lower-greek}.mw-parser-output .reflist-lower-roman{list-style-type:lower-roman}</style><div class="reflist reflist-columns references-column-width" style="column-width: 32em;"> <ol class="references"> <li id="cite_note-marathe-1"><span class="mw-cite-backlink">^ <a href="#cite_ref-marathe_1-0"><sup><i><b>a</b></i></sup></a> <a href="#cite_ref-marathe_1-1"><sup><i><b>b</b></i></sup></a></span> <span class="reference-text"><style data-mw-deduplicate="TemplateStyles:r1238218222">.mw-parser-output cite.citation{font-style:inherit;word-wrap:break-word}.mw-parser-output .citation q{quotes:"\"""\"""'""'"}.mw-parser-output .citation:target{background-color:rgba(0,127,255,0.133)}.mw-parser-output .id-lock-free.id-lock-free a{background:url("//upload.wikimedia.org/wikipedia/commons/6/65/Lock-green.svg")right 0.1em center/9px no-repeat}.mw-parser-output .id-lock-limited.id-lock-limited a,.mw-parser-output .id-lock-registration.id-lock-registration a{background:url("//upload.wikimedia.org/wikipedia/commons/d/d6/Lock-gray-alt-2.svg")right 0.1em center/9px no-repeat}.mw-parser-output .id-lock-subscription.id-lock-subscription a{background:url("//upload.wikimedia.org/wikipedia/commons/a/aa/Lock-red-alt-2.svg")right 0.1em center/9px no-repeat}.mw-parser-output .cs1-ws-icon a{background:url("//upload.wikimedia.org/wikipedia/commons/4/4c/Wikisource-logo.svg")right 0.1em center/12px no-repeat}body:not(.skin-timeless):not(.skin-minerva) .mw-parser-output .id-lock-free a,body:not(.skin-timeless):not(.skin-minerva) .mw-parser-output .id-lock-limited a,body:not(.skin-timeless):not(.skin-minerva) .mw-parser-output .id-lock-registration a,body:not(.skin-timeless):not(.skin-minerva) .mw-parser-output .id-lock-subscription a,body:not(.skin-timeless):not(.skin-minerva) .mw-parser-output .cs1-ws-icon a{background-size:contain;padding:0 1em 0 0}.mw-parser-output .cs1-code{color:inherit;background:inherit;border:none;padding:inherit}.mw-parser-output .cs1-hidden-error{display:none;color:var(--color-error,#d33)}.mw-parser-output .cs1-visible-error{color:var(--color-error,#d33)}.mw-parser-output .cs1-maint{display:none;color:#085;margin-left:0.3em}.mw-parser-output .cs1-kern-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right{padding-right:0.2em}.mw-parser-output .citation .mw-selflink{font-weight:inherit}@media screen{.mw-parser-output .cs1-format{font-size:95%}html.skin-theme-clientpref-night .mw-parser-output .cs1-maint{color:#18911f}}@media screen and (prefers-color-scheme:dark){html.skin-theme-clientpref-os .mw-parser-output .cs1-maint{color:#18911f}}</style><cite id="CITEREFMaratheRaynerJonesHorowitz2013" class="citation journal cs1">Marathe CS, Rayner CK, Jones KL, Horowitz M (June 2013). "Glucagon-like peptides 1 and 2 in health and disease: a review". <i>Peptides</i>. <b>44</b>: 75–86. <a href="/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<a rel="nofollow" class="external text" href="https://doi.org/10.1016%2Fj.peptides.2013.01.014">10.1016/j.peptides.2013.01.014</a>. <a href="/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/23523778">23523778</a>. <a href="/wiki/S2CID_(identifier)" class="mw-redirect" title="S2CID (identifier)">S2CID</a> <a rel="nofollow" class="external text" href="https://api.semanticscholar.org/CorpusID:22641629">22641629</a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=Peptides&rft.atitle=Glucagon-like+peptides+1+and+2+in+health+and+disease%3A+a+review&rft.volume=44&rft.pages=75-86&rft.date=2013-06&rft_id=https%3A%2F%2Fapi.semanticscholar.org%2FCorpusID%3A22641629%23id-name%3DS2CID&rft_id=info%3Apmid%2F23523778&rft_id=info%3Adoi%2F10.1016%2Fj.peptides.2013.01.014&rft.aulast=Marathe&rft.aufirst=CS&rft.au=Rayner%2C+CK&rft.au=Jones%2C+KL&rft.au=Horowitz%2C+M&rfr_id=info%3Asid%2Fen.wikipedia.org%3AGlucagon-like+peptide-1" class="Z3988"></span></span> </li> <li id="cite_note-drucker-2"><span class="mw-cite-backlink">^ <a href="#cite_ref-drucker_2-0"><sup><i><b>a</b></i></sup></a> <a href="#cite_ref-drucker_2-1"><sup><i><b>b</b></i></sup></a> <a href="#cite_ref-drucker_2-2"><sup><i><b>c</b></i></sup></a> <a href="#cite_ref-drucker_2-3"><sup><i><b>d</b></i></sup></a> <a href="#cite_ref-drucker_2-4"><sup><i><b>e</b></i></sup></a> <a href="#cite_ref-drucker_2-5"><sup><i><b>f</b></i></sup></a></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFBaggioDrucker2007" class="citation journal cs1">Baggio LL, Drucker DJ (May 2007). <a rel="nofollow" class="external text" href="https://doi.org/10.1053%2Fj.gastro.2007.03.054">"Biology of incretins: GLP-1 and GIP"</a>. <i>Gastroenterology</i>. <b>132</b> (6): 2131–57. <a href="/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<span class="id-lock-free" title="Freely accessible"><a rel="nofollow" class="external text" href="https://doi.org/10.1053%2Fj.gastro.2007.03.054">10.1053/j.gastro.2007.03.054</a></span>. <a href="/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/17498508">17498508</a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=Gastroenterology&rft.atitle=Biology+of+incretins%3A+GLP-1+and+GIP&rft.volume=132&rft.issue=6&rft.pages=2131-57&rft.date=2007-05&rft_id=info%3Adoi%2F10.1053%2Fj.gastro.2007.03.054&rft_id=info%3Apmid%2F17498508&rft.aulast=Baggio&rft.aufirst=LL&rft.au=Drucker%2C+DJ&rft_id=https%3A%2F%2Fdoi.org%2F10.1053%252Fj.gastro.2007.03.054&rfr_id=info%3Asid%2Fen.wikipedia.org%3AGlucagon-like+peptide-1" class="Z3988"></span></span> </li> <li id="cite_note-jjholst-3"><span class="mw-cite-backlink">^ <a href="#cite_ref-jjholst_3-0"><sup><i><b>a</b></i></sup></a> <a href="#cite_ref-jjholst_3-1"><sup><i><b>b</b></i></sup></a> <a href="#cite_ref-jjholst_3-2"><sup><i><b>c</b></i></sup></a> <a href="#cite_ref-jjholst_3-3"><sup><i><b>d</b></i></sup></a> <a href="#cite_ref-jjholst_3-4"><sup><i><b>e</b></i></sup></a></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFHolst2007" class="citation journal cs1">Holst JJ (October 2007). 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peptide-2">GLP2</a></li></ul></li></ul> </div></td></tr></tbody></table></div> <div class="navbox-styles"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1129693374"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1236075235"></div><div role="navigation" class="navbox" aria-labelledby="Oral_diabetes_medication,_insulins_and_insulin_analogs,_and_other_drugs_used_in_diabetes_(A10)" style="padding:3px"><table class="nowraplinks mw-collapsible expanded navbox-inner" style="border-spacing:0;background:transparent;color:inherit"><tbody><tr><th scope="col" class="navbox-title" colspan="2"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1129693374"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1239400231"><div class="navbar plainlinks hlist navbar-mini"><ul><li class="nv-view"><a href="/wiki/Template:Oral_hypoglycemics_and_insulin_analogs" title="Template:Oral hypoglycemics and insulin analogs"><abbr title="View this template">v</abbr></a></li><li class="nv-talk"><a href="/wiki/Template_talk:Oral_hypoglycemics_and_insulin_analogs" title="Template talk:Oral hypoglycemics and insulin analogs"><abbr title="Discuss this template">t</abbr></a></li><li class="nv-edit"><a href="/wiki/Special:EditPage/Template:Oral_hypoglycemics_and_insulin_analogs" title="Special:EditPage/Template:Oral hypoglycemics and insulin analogs"><abbr title="Edit this template">e</abbr></a></li></ul></div><div id="Oral_diabetes_medication,_insulins_and_insulin_analogs,_and_other_drugs_used_in_diabetes_(A10)" style="font-size:114%;margin:0 4em">Oral <a href="/wiki/Diabetes_medication" title="Diabetes medication">diabetes medication</a>, <a href="/wiki/Insulin" title="Insulin">insulins</a> and <a href="/wiki/Insulin_analog" title="Insulin analog">insulin analogs</a>, and other drugs used in diabetes (<a href="/wiki/ATC_code_A10" title="ATC code A10">A10</a>)</div></th></tr><tr><td colspan="2" class="navbox-list navbox-odd hlist" style="width:100%;padding:0"><div style="padding:0 0.25em"></div><table class="nowraplinks mw-collapsible mw-collapsed navbox-subgroup" style="border-spacing:0"><tbody><tr><th scope="col" class="navbox-title" colspan="2"><div id="Insulins_/_insulin_analogs" style="font-size:114%;margin:0 4em"><a href="/wiki/Insulin" title="Insulin">Insulins</a> / <a href="/wiki/Insulin_analog" title="Insulin analog">insulin analogs</a></div></th></tr><tr><td colspan="2" class="navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"></div><table class="nowraplinks navbox-subgroup" style="border-spacing:0"><tbody><tr><th scope="row" class="navbox-group" style="width:1%"><i>fast-acting</i></th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Insulin_aspart" title="Insulin aspart">Insulin aspart</a></li> <li><a href="/wiki/Insulin_glulisine" title="Insulin glulisine">Insulin glulisine</a></li> <li><a href="/wiki/Insulin_lispro" title="Insulin lispro">Insulin lispro</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><i>short-acting</i></th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Regular_insulin" title="Regular insulin">Regular insulin</a><sup>#</sup></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><i>long-acting</i></th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Insulin_detemir" title="Insulin detemir">Insulin detemir</a><sup>#</sup></li> <li><a href="/wiki/Insulin_glargine" title="Insulin glargine">Insulin glargine</a><sup>#</sup> (<a href="/wiki/Insulin_glargine/lixisenatide" title="Insulin glargine/lixisenatide">+lixisenatide</a>)</li> <li><a href="/wiki/NPH_insulin" title="NPH insulin">NPH insulin</a></li> <li><a href="/wiki/Lente_insulin" title="Lente insulin">Lente insulin</a><sup>‡</sup></li> <li><a href="/wiki/Ultralente_insulin" title="Ultralente insulin">Ultralente insulin</a><sup>‡</sup></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><i>ultra-long-acting</i></th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Insulin_degludec" title="Insulin degludec">Insulin degludec</a><sup>#</sup> (<a href="/wiki/Insulin_degludec/insulin_aspart" title="Insulin degludec/insulin aspart">+insulin aspart</a>, <a href="/wiki/Insulin_degludec/liraglutide" title="Insulin degludec/liraglutide">+liraglutide</a>)</li> <li><a href="/wiki/Insulin_icodec" title="Insulin icodec">Insulin icodec</a><sup>†</sup> (<a href="/wiki/Insulin_icodec/semaglutide" title="Insulin icodec/semaglutide">+semaglutide</a>)</li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><i><a href="/wiki/Inhalable_insulin" title="Inhalable insulin">inhalable</a></i></th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li>Exubera<sup>‡</sup></li> <li>Afrezza</li></ul> </div></td></tr></tbody></table><div> <div class="hlist"> <ul><li><sup>#</sup><a href="/wiki/WHO_Model_List_of_Essential_Medicines" title="WHO Model List of Essential Medicines">WHO-EM</a></li> <li><sup>‡</sup><a href="/wiki/List_of_withdrawn_drugs" title="List of withdrawn drugs">Withdrawn</a> from market</li> <li><a href="/wiki/Clinical_trial" title="Clinical trial">Clinical trials</a>: <ul><li><sup>†</sup><a href="/wiki/Phases_of_clinical_research#Phase_III" title="Phases of clinical research">Phase III</a></li> <li><sup>§</sup>Never to phase III</li></ul></li></ul> </div></div></td></tr></tbody></table><div></div></td></tr><tr><td colspan="2" class="navbox-list navbox-odd hlist" style="width:100%;padding:0"><div style="padding:0 0.25em"></div><table class="nowraplinks mw-collapsible mw-collapsed navbox-subgroup" style="border-spacing:0"><tbody><tr><th scope="col" class="navbox-title" colspan="2"><div id="Non-insulins" style="font-size:114%;margin:0 4em">Non-insulins</div></th></tr><tr><td colspan="2" class="navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"></div><table class="nowraplinks navbox-subgroup" style="border-spacing:0"><tbody><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Anti-diabetic_medication#Sensitizers" class="mw-redirect" title="Anti-diabetic medication">Insulin sensitizers</a></th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"></div><table class="nowraplinks navbox-subgroup" style="border-spacing:0"><tbody><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Biguanide" title="Biguanide">Biguanides</a></th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Buformin" title="Buformin">Buformin</a><sup>‡</sup></li> <li><a href="/wiki/Metformin" title="Metformin">Metformin</a><sup>#</sup></li> <li><a href="/wiki/Phenformin" title="Phenformin">Phenformin</a><sup>‡</sup></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Thiazolidinedione" title="Thiazolidinedione">TZDs</a>/"glitazones" (<a href="/wiki/PPAR_agonist" title="PPAR agonist">PPAR</a>)</th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Ciglitazone" title="Ciglitazone">Ciglitazone</a><sup>§</sup></li> <li><a href="/wiki/Darglitazone" title="Darglitazone">Darglitazone</a><sup>§</sup></li> <li><a href="/wiki/Englitazone" title="Englitazone">Englitazone</a><sup>§</sup></li> <li><a href="/wiki/Lobeglitazone" title="Lobeglitazone">Lobeglitazone</a></li> <li><a href="/wiki/Netoglitazone" title="Netoglitazone">Netoglitazone</a><sup>§</sup></li> <li><a href="/wiki/Pioglitazone" title="Pioglitazone">Pioglitazone</a></li> <li><a href="/wiki/Rivoglitazone" title="Rivoglitazone">Rivoglitazone</a><sup>†</sup></li> <li><a href="/wiki/Rosiglitazone" title="Rosiglitazone">Rosiglitazone</a></li> <li><a href="/wiki/Troglitazone" title="Troglitazone">Troglitazone</a><sup>‡</sup></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/PPAR_agonist#Dual_PPAR_agonists" title="PPAR agonist">Dual PPAR agonists</a></th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Aleglitazar" title="Aleglitazar">Aleglitazar</a><sup>†</sup></li> <li><a href="/wiki/Muraglitazar" title="Muraglitazar">Muraglitazar</a><sup>§</sup></li> <li><a href="/wiki/Saroglitazar" title="Saroglitazar">Saroglitazar</a></li> <li><a href="/wiki/Tesaglitazar" title="Tesaglitazar">Tesaglitazar</a><sup>§</sup></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Amylin" title="Amylin">Amylin</a> analogs and <a href="/wiki/DACRA" class="mw-redirect" title="DACRA">DACRAs</a></th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Cagrilintide" title="Cagrilintide">Cagrilintide</a><sup>§</sup></li> <li><a href="/wiki/Pramlintide" title="Pramlintide">Pramlintide</a></li></ul> </div></td></tr></tbody></table><div></div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Anti-diabetic_medication#Secretagogues" class="mw-redirect" title="Anti-diabetic medication">Secretagogues</a></th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"></div><table class="nowraplinks navbox-subgroup" style="border-spacing:0"><tbody><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/ATP-sensitive_potassium_channel" title="ATP-sensitive potassium channel">K<sup>+</sup><sub>ATP</sub></a></th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"></div><table class="nowraplinks navbox-subgroup" style="border-spacing:0"><tbody><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Sulfonylurea" title="Sulfonylurea">Sulfonylureas</a></th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><i>1st generation</i>: <a href="/wiki/Acetohexamide" title="Acetohexamide">Acetohexamide</a></li> <li><a href="/wiki/Carbutamide" title="Carbutamide">Carbutamide</a></li> <li><a href="/wiki/Chlorpropamide" title="Chlorpropamide">Chlorpropamide</a></li> <li><a href="/w/index.php?title=Glycyclamide&action=edit&redlink=1" class="new" title="Glycyclamide (page does not exist)">Glycyclamide</a></li> <li><a href="/wiki/Metahexamide" title="Metahexamide">Metahexamide</a></li> <li><a href="/wiki/Tolazamide" title="Tolazamide">Tolazamide</a></li> <li><a href="/wiki/Tolbutamide" title="Tolbutamide">Tolbutamide</a></li></ul> <ul><li><i>2nd generation</i>: <a href="/wiki/Glibenclamide" title="Glibenclamide">Glibenclamide (glyburide)</a></li> <li><a href="/wiki/Glibornuride" title="Glibornuride">Glibornuride</a></li> <li><a href="/wiki/Glicaramide" title="Glicaramide">Glicaramide</a></li> <li><a href="/wiki/Gliclazide" title="Gliclazide">Gliclazide</a><sup>#</sup></li> <li><a href="/wiki/Glimepiride" title="Glimepiride">Glimepiride</a></li> <li><a href="/wiki/Glipizide" title="Glipizide">Glipizide</a></li> <li><a href="/wiki/Gliquidone" title="Gliquidone">Gliquidone</a></li> <li><a href="/wiki/Glisoxepide" title="Glisoxepide">Glisoxepide</a></li> <li><a href="/wiki/Glyclopyramide" title="Glyclopyramide">Glyclopyramide</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Meglitinide" title="Meglitinide">Meglitinides</a>/"glinides"</th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Mitiglinide" title="Mitiglinide">Mitiglinide</a></li> <li><a href="/wiki/Nateglinide" title="Nateglinide">Nateglinide</a></li> <li><a href="/wiki/Repaglinide" title="Repaglinide">Repaglinide</a></li></ul> </div></td></tr></tbody></table><div></div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Glucagon-like_peptide-1_receptor_agonist" class="mw-redirect" title="Glucagon-like peptide-1 receptor agonist">GLP-1 receptor agonists</a></th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Albiglutide" title="Albiglutide">Albiglutide</a><sup>‡</sup></li> <li><a href="/wiki/Danuglipron" title="Danuglipron">Danuglipron</a><sup>†</sup></li> <li><a href="/wiki/Dulaglutide" title="Dulaglutide">Dulaglutide</a></li> <li><a href="/wiki/Exenatide" title="Exenatide">Exenatide</a></li> <li><a href="/wiki/Liraglutide" title="Liraglutide">Liraglutide</a></li> <li><a href="/wiki/Lixisenatide" title="Lixisenatide">Lixisenatide</a></li> <li><a href="/wiki/Orforglipron" title="Orforglipron">Orforglipron</a><sup>§</sup></li> <li><a href="/wiki/Semaglutide" title="Semaglutide">Semaglutide</a></li> <li><a href="/wiki/Taspoglutide" title="Taspoglutide">Taspoglutide</a><sup>†</sup></li></ul> </div><table class="nowraplinks navbox-subgroup" style="border-spacing:0"><tbody><tr><th id="GLP1_poly-agonist_peptides" scope="row" class="navbox-group" style="width:1%"><a href="/wiki/GLP1_poly-agonist_peptides" title="GLP1 poly-agonist peptides">GLP1 poly-agonist peptides</a></th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Mazdutide" title="Mazdutide">Mazdutide</a> (GLP-1/<a href="/wiki/Glucagon_receptor" title="Glucagon receptor">GCGR</a>)</li> <li><a href="/wiki/Retatrutide" title="Retatrutide">Retatrutide</a><sup>§</sup> (GLP-1/GIP/GCGR)</li> <li><a href="/wiki/Tirzepatide" title="Tirzepatide">Tirzepatide</a> (GLP-1/GIP)</li></ul> </div></td></tr></tbody></table><div> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Dipeptidyl_peptidase-4_inhibitor" title="Dipeptidyl peptidase-4 inhibitor">DPP-4 inhibitors</a>/"gliptins"</th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Alogliptin" title="Alogliptin">Alogliptin</a></li> <li><a href="/wiki/Anagliptin" title="Anagliptin">Anagliptin</a></li> <li><a href="/wiki/Evogliptin" title="Evogliptin">Evogliptin</a></li> <li><a href="/w/index.php?title=Garvagliptin&action=edit&redlink=1" class="new" title="Garvagliptin (page does not exist)">Garvagliptin</a></li> <li><a href="/wiki/Gemigliptin" title="Gemigliptin">Gemigliptin</a></li> <li><a href="/wiki/Gosogliptin" title="Gosogliptin">Gosogliptin</a></li> <li><a href="/wiki/Linagliptin" title="Linagliptin">Linagliptin</a></li> <li><a href="/w/index.php?title=Melogliptin&action=edit&redlink=1" class="new" title="Melogliptin (page does not exist)">Melogliptin</a></li> <li><a href="/wiki/Omarigliptin" title="Omarigliptin">Omarigliptin</a></li> <li><a href="/wiki/Saxagliptin" title="Saxagliptin">Saxagliptin</a></li> <li><a href="/wiki/Sitagliptin" title="Sitagliptin">Sitagliptin</a></li> <li><a href="/wiki/Teneligliptin" title="Teneligliptin">Teneligliptin</a></li> <li><a href="/wiki/Trelagliptin" title="Trelagliptin">Trelagliptin</a></li> <li><a href="/wiki/Vildagliptin" title="Vildagliptin">Vildagliptin</a></li></ul> </div></td></tr></tbody></table><div></div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%">Other</th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"></div><table class="nowraplinks navbox-subgroup" style="border-spacing:0"><tbody><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Aldose_reductase_inhibitor" title="Aldose reductase inhibitor">Aldose reductase inhibitors</a></th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Epalrestat" title="Epalrestat">Epalrestat</a></li> <li><a href="/wiki/Fidarestat" title="Fidarestat">Fidarestat</a><sup>§</sup></li> <li><a href="/wiki/Ranirestat" title="Ranirestat">Ranirestat</a><sup>†</sup></li> <li><a href="/wiki/Tolrestat" title="Tolrestat">Tolrestat</a><sup>‡</sup></li> <li><a href="/wiki/Zenarestat" title="Zenarestat">Zenarestat</a><sup>§</sup></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Alpha-glucosidase_inhibitor" title="Alpha-glucosidase inhibitor">Alpha-glucosidase inhibitors</a></th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Acarbose" title="Acarbose">Acarbose</a></li> <li><a href="/wiki/Miglitol" title="Miglitol">Miglitol</a></li> <li><a href="/wiki/Voglibose" title="Voglibose">Voglibose</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Gliflozin" class="mw-redirect" title="Gliflozin">SGLT2 inhibitors</a>/"gliflozins"</th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Canagliflozin" title="Canagliflozin">Canagliflozin</a></li> <li><a href="/wiki/Dapagliflozin" title="Dapagliflozin">Dapagliflozin</a></li> <li><a href="/wiki/Empagliflozin" title="Empagliflozin">Empagliflozin</a><sup>#</sup></li> <li><a href="/wiki/Ertugliflozin" title="Ertugliflozin">Ertugliflozin</a></li> <li><a href="/wiki/Ipragliflozin" title="Ipragliflozin">Ipragliflozin</a></li> <li><a href="/wiki/Luseogliflozin" title="Luseogliflozin">Luseogliflozin</a></li> <li><a href="/wiki/Remogliflozin_etabonate" title="Remogliflozin etabonate">Remogliflozin</a><sup>§</sup></li> <li><a href="/wiki/Sergliflozin_etabonate" title="Sergliflozin etabonate">Sergliflozin</a><sup>§</sup></li> <li><a href="/wiki/Sotagliflozin" title="Sotagliflozin">Sotagliflozin</a></li> <li><a href="/wiki/Tofogliflozin" title="Tofogliflozin">Tofogliflozin</a><sup>†</sup></li> <li><a href="/wiki/Velagliflozin" title="Velagliflozin">Velagliflozin</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%">Other</th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Benfluorex" title="Benfluorex">Benfluorex</a><sup>‡</sup></li> <li><a href="/wiki/Bromocriptine" title="Bromocriptine">Bromocriptine</a></li> <li><a href="/wiki/Imeglimin" title="Imeglimin">Imeglimin</a></li></ul> </div></td></tr></tbody></table><div></div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Combination_drug" title="Combination drug">Combinations</a></th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"></div><table class="nowraplinks navbox-subgroup" style="border-spacing:0"><tbody><tr><td colspan="2" class="navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Alogliptin/metformin" class="mw-redirect" title="Alogliptin/metformin">Alogliptin/metformin</a></li> <li><a href="/wiki/Canagliflozin/metformin" title="Canagliflozin/metformin">Canagliflozin/metformin</a></li> <li><a href="/wiki/Cagrilintide/semaglutide" title="Cagrilintide/semaglutide">Cagrilintide/semaglutide</a><sup>§</sup></li> <li><a href="/wiki/Dapagliflozin/metformin" title="Dapagliflozin/metformin">Dapagliflozin/metformin</a></li> <li><a href="/wiki/Dapagliflozin/saxagliptin" title="Dapagliflozin/saxagliptin">Dapagliflozin/saxagliptin</a></li> <li><a href="/wiki/Dapagliflozin/saxagliptin/metformin" title="Dapagliflozin/saxagliptin/metformin">Dapagliflozin/saxagliptin/metformin</a></li> <li><a href="/wiki/Empagliflozin/linagliptin" title="Empagliflozin/linagliptin">Empagliflozin/linagliptin</a></li> <li><a href="/wiki/Empagliflozin/metformin" title="Empagliflozin/metformin">Empagliflozin/metformin</a></li> <li><a href="/w/index.php?title=Gemigliptin/rosuvastatin&action=edit&redlink=1" class="new" title="Gemigliptin/rosuvastatin (page does not exist)">Gemigliptin/rosuvastatin</a></li> <li><a href="/wiki/Glibenclamide/metformin" title="Glibenclamide/metformin">Glibenclamide (glyburide)/metformin</a></li> <li><a href="/w/index.php?title=Glimepiride/rosiglitazone&action=edit&redlink=1" class="new" title="Glimepiride/rosiglitazone (page does not exist)">Glimepiride/rosiglitazone</a></li> <li><a href="/wiki/Linagliptin/metformin" class="mw-redirect" title="Linagliptin/metformin">Linagliptin/metformin</a></li> <li><a href="/w/index.php?title=Metformin/acarbose&action=edit&redlink=1" class="new" title="Metformin/acarbose (page does not exist)">Metformin/acarbose</a></li> <li><a href="/wiki/Metformin/ertugliflozin" class="mw-redirect" title="Metformin/ertugliflozin">Metformin/ertugliflozin</a></li> <li><a href="/w/index.php?title=Metformin/evogliptin&action=edit&redlink=1" class="new" title="Metformin/evogliptin (page does not exist)">Metformin/evogliptin</a></li> <li><a href="/w/index.php?title=Metformin/gemigliptin&action=edit&redlink=1" class="new" title="Metformin/gemigliptin (page does not exist)">Metformin/gemigliptin</a></li> <li><a href="/w/index.php?title=Metformin/repaglinide&action=edit&redlink=1" class="new" title="Metformin/repaglinide (page does not exist)">Metformin/repaglinide</a></li> <li><a href="/w/index.php?title=Metformin/sulfonylureas&action=edit&redlink=1" class="new" title="Metformin/sulfonylureas (page does not exist)">Metformin/sulfonylureas</a></li> <li><a href="/w/index.php?title=Metformin/teneligliptin&action=edit&redlink=1" class="new" title="Metformin/teneligliptin (page does not exist)">Metformin/teneligliptin</a></li> <li><a href="/w/index.php?title=Phenformin/sulfonylureas&action=edit&redlink=1" class="new" title="Phenformin/sulfonylureas (page does not exist)">Phenformin/sulfonylureas</a></li> <li><a href="/wiki/Pioglitazone/alogliptin" class="mw-redirect" title="Pioglitazone/alogliptin">Pioglitazone/alogliptin</a></li> <li><a href="/wiki/Pioglitazone/glimepiride" title="Pioglitazone/glimepiride">Pioglitazone/glimepiride</a></li> <li><a href="/wiki/Pioglitazone/metformin" title="Pioglitazone/metformin">Pioglitazone/metformin</a></li> <li><a href="/w/index.php?title=Pioglitazone/sitagliptin&action=edit&redlink=1" class="new" title="Pioglitazone/sitagliptin (page does not exist)">Pioglitazone/sitagliptin</a></li> <li><a href="/wiki/Rosiglitazone/metformin" class="mw-redirect" title="Rosiglitazone/metformin">Rosiglitazone/metformin</a></li> <li><a href="/wiki/Saxagliptin/metformin" class="mw-redirect" title="Saxagliptin/metformin">Saxagliptin/metformin</a></li> <li><a href="/wiki/Dapagliflozin/sitagliptin" title="Dapagliflozin/sitagliptin">Sitagliptin/dapagliflozin</a></li> <li><a href="/w/index.php?title=Sitagliptin/ertugliflozin&action=edit&redlink=1" class="new" title="Sitagliptin/ertugliflozin (page does not exist)">Sitagliptin/ertugliflozin</a></li> <li><a href="/wiki/Sitagliptin/metformin" title="Sitagliptin/metformin">Sitagliptin/metformin</a></li> <li><a href="/wiki/Simvastatin/sitagliptin" class="mw-redirect" title="Simvastatin/sitagliptin">Sitagliptin/simvastatin</a></li> <li><a href="/wiki/Vildagliptin/metformin" title="Vildagliptin/metformin">Vildagliptin/metformin</a></li></ul> </div></td></tr></tbody></table><div></div></td></tr></tbody></table><div> <div class="hlist"> <ul><li><sup>#</sup><a href="/wiki/WHO_Model_List_of_Essential_Medicines" title="WHO Model List of Essential Medicines">WHO-EM</a></li> <li><sup>‡</sup><a href="/wiki/List_of_withdrawn_drugs" title="List of withdrawn drugs">Withdrawn</a> from market</li> <li><a href="/wiki/Clinical_trial" title="Clinical trial">Clinical trials</a>: <ul><li><sup>†</sup><a href="/wiki/Phases_of_clinical_research#Phase_III" title="Phases of clinical research">Phase III</a></li> <li><sup>§</sup>Never to phase III</li></ul></li></ul> </div></div></td></tr></tbody></table><div></div></td></tr></tbody></table></div> <p><br /> American diabetes association:link-<a rel="nofollow" class="external free" href="http://diabetes.diabetesjournals.org/content/56/1/8.full">http://diabetes.diabetesjournals.org/content/56/1/8.full</a> </p>    </div><noscript><img src="https://login.wikimedia.org/wiki/Special:CentralAutoLogin/start?type=1x1" alt="" width="1" height="1" style="border: none; position: absolute;"></noscript> <div class="printfooter" data-nosnippet="">Retrieved from "<a dir="ltr" href="https://en.wikipedia.org/w/index.php?title=Glucagon-like_peptide-1&oldid=1259103048">https://en.wikipedia.org/w/index.php?title=Glucagon-like_peptide-1&oldid=1259103048</a>"</div></div> <div id="catlinks" class="catlinks" data-mw="interface"><div id="mw-normal-catlinks" class="mw-normal-catlinks"><a href="/wiki/Help:Category" title="Help:Category">Categories</a>: <ul><li><a href="/wiki/Category:Anti-diabetic_drugs" 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