Orforglipron, a novel non‐peptide oral daily glucagon‐like peptide‐1 receptor agonist as an anti‐obesity medicine: A systematic review and meta‐analysis

Background Orforglipron is a novel once‐daily oral non‐peptide glucagon‐like peptide‐1 receptor agonist with several recently published randomized controlled trials (RCTs) evaluating its role in diabetes and obesity. No meta‐analysis has analyzed the efficacy and safety of orforglipron; this meta‐an...

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Published in:Obesity science & practice 2024-04, Vol.10 (2), p.e743-n/a
Main Authors: Dutta, Deep, Nagendra, Lakshmi, Anne, Beatrice, Kumar, Manoj, Sharma, Meha, Kamrul‐Hasan, A. B. M.
Format: Article
Language:English
Subjects:
Agonists
Bias
Blood pressure
Body mass index
Body weight loss
Clinical trials
Constipation
Diabetes
Diabetes mellitus
Drug dosages
emerging treatments
Gastroesophageal reflux
GLP1RA
Glucagon
Glucagon-like peptide 1
Hemoglobin
medications
Medicine
Meta-analysis
Obesity
orforglipron
Peptides
Placebos
Review
Side effects
Systematic review
Weight control
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container_title Obesity science & practice
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creator Dutta, Deep
Nagendra, Lakshmi
Anne, Beatrice
Kumar, Manoj
Sharma, Meha
Kamrul‐Hasan, A. B. M.
description Background Orforglipron is a novel once‐daily oral non‐peptide glucagon‐like peptide‐1 receptor agonist with several recently published randomized controlled trials (RCTs) evaluating its role in diabetes and obesity. No meta‐analysis has analyzed the efficacy and safety of orforglipron; this meta‐analysis aimed to address this knowledge gap. Methods A systematic search was conducted in electronic databases to identify RCTs that included individuals with obesity who were administered orforglipron and compared to either a placebo or an active comparator. The primary outcome of interest was the percent change in body weight. Results From 12 initially screened articles, data from three RCTs involving 774 people were analyzed with a follow‐up duration of up to 36 weeks. Compared to placebo, patients receiving orforglipron 12 mg/day (mean difference (MD), MD −5.48%, 95% CI [−7.64, −3.33], p 
doi_str_mv 10.1002/osp4.743
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B. M.</creator><creatorcontrib>Dutta, Deep ; Nagendra, Lakshmi ; Anne, Beatrice ; Kumar, Manoj ; Sharma, Meha ; Kamrul‐Hasan, A. B. M.</creatorcontrib><description>Background Orforglipron is a novel once‐daily oral non‐peptide glucagon‐like peptide‐1 receptor agonist with several recently published randomized controlled trials (RCTs) evaluating its role in diabetes and obesity. No meta‐analysis has analyzed the efficacy and safety of orforglipron; this meta‐analysis aimed to address this knowledge gap. Methods A systematic search was conducted in electronic databases to identify RCTs that included individuals with obesity who were administered orforglipron and compared to either a placebo or an active comparator. The primary outcome of interest was the percent change in body weight. Results From 12 initially screened articles, data from three RCTs involving 774 people were analyzed with a follow‐up duration of up to 36 weeks. Compared to placebo, patients receiving orforglipron 12 mg/day (mean difference (MD), MD −5.48%, 95% CI [−7.64, −3.33], p &lt; 0.01), 24 mg/day (MD −8.51%, 95% confidence interval (CI) [−9.88, −7.14], p &lt; 0.01), 36 mg/day (MD −8.84%, 95% CI [−11.68, −6.00], p &lt; 0.01) and 45 mg/day (MD −8.24%, 95% CI [−12.84, −3.63], p &lt; 0.01) had a significantly greater percent reduction in body weight. The percentage of patients being able to achieve &gt;15% weight loss from baseline was significantly higher with orforglipron 24 mg/day [Odds ratio (OR) 21.90 (95% CI [4.06, 118.15], p = 0.0003), 36 mg/day (OR 17.43, 95% CI [3.18, 95.66], p = 0.001) and 45 mg/day (OR 23.17, 95% CI [4.37, 123.03], p = 0.0002). Total but not severe adverse events were significantly higher with all the doses of orforglipron compared to placebo, with the hazard ratios being higher with higher doses. Gastrointestinal side‐effects were predominant side effects, being dose‐dependent, with nausea, vomiting, constipation, and gastroesophageal reflux being the predominant ones. Conclusion Orforglipron at 24–45 mg/day doses is an effective weight loss medication. The efficacy versus side effect profile suggests that 24–36 mg/day is the most optimal dose for orforglipron as an anti‐obesity medicine. Orforglipron at doses of 24–45 mg/day is an effective weight loss medication. The efficacy versus side effect profile suggests that 24–36 mg/day is the most optimal dose for orforglipron as an anti‐obesity medicine.</description><identifier>ISSN: 2055-2238</identifier><identifier>EISSN: 2055-2238</identifier><identifier>DOI: 10.1002/osp4.743</identifier><identifier>PMID: 38414573</identifier><language>eng</language><publisher>United States: John Wiley &amp; Sons, Inc</publisher><subject>Agonists ; Bias ; Blood pressure ; Body mass index ; Body weight loss ; Clinical trials ; Constipation ; Diabetes ; Diabetes mellitus ; Drug dosages ; emerging treatments ; Gastroesophageal reflux ; GLP1RA ; Glucagon ; Glucagon-like peptide 1 ; Hemoglobin ; medications ; Medicine ; Meta-analysis ; Obesity ; orforglipron ; Peptides ; Placebos ; Review ; Side effects ; Systematic review ; Weight control</subject><ispartof>Obesity science &amp; practice, 2024-04, Vol.10 (2), p.e743-n/a</ispartof><rights>2024 The Authors. Obesity Science &amp; Practice published by World Obesity and The Obesity Society and John Wiley &amp; Sons Ltd.</rights><rights>2024. This work is published under http://creativecommons.org/licenses/by-nc/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c4663-761ed1ecb6c4641f3d31a9a5fb0787aedfd9c80e1744c6e0e5feba3ff239541f3</cites><orcidid>0000-0003-0249-2523 ; 0000-0003-4915-8805 ; 0000-0001-6865-5554 ; 0000-0002-5681-6522</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/3046367786/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/3046367786?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,11562,25753,27924,27925,37012,37013,44590,46052,46476,53791,53793,75126</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38414573$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Dutta, Deep</creatorcontrib><creatorcontrib>Nagendra, Lakshmi</creatorcontrib><creatorcontrib>Anne, Beatrice</creatorcontrib><creatorcontrib>Kumar, Manoj</creatorcontrib><creatorcontrib>Sharma, Meha</creatorcontrib><creatorcontrib>Kamrul‐Hasan, A. B. M.</creatorcontrib><title>Orforglipron, a novel non‐peptide oral daily glucagon‐like peptide‐1 receptor agonist as an anti‐obesity medicine: A systematic review and meta‐analysis</title><title>Obesity science &amp; practice</title><addtitle>Obes Sci Pract</addtitle><description>Background Orforglipron is a novel once‐daily oral non‐peptide glucagon‐like peptide‐1 receptor agonist with several recently published randomized controlled trials (RCTs) evaluating its role in diabetes and obesity. No meta‐analysis has analyzed the efficacy and safety of orforglipron; this meta‐analysis aimed to address this knowledge gap. Methods A systematic search was conducted in electronic databases to identify RCTs that included individuals with obesity who were administered orforglipron and compared to either a placebo or an active comparator. The primary outcome of interest was the percent change in body weight. Results From 12 initially screened articles, data from three RCTs involving 774 people were analyzed with a follow‐up duration of up to 36 weeks. Compared to placebo, patients receiving orforglipron 12 mg/day (mean difference (MD), MD −5.48%, 95% CI [−7.64, −3.33], p &lt; 0.01), 24 mg/day (MD −8.51%, 95% confidence interval (CI) [−9.88, −7.14], p &lt; 0.01), 36 mg/day (MD −8.84%, 95% CI [−11.68, −6.00], p &lt; 0.01) and 45 mg/day (MD −8.24%, 95% CI [−12.84, −3.63], p &lt; 0.01) had a significantly greater percent reduction in body weight. The percentage of patients being able to achieve &gt;15% weight loss from baseline was significantly higher with orforglipron 24 mg/day [Odds ratio (OR) 21.90 (95% CI [4.06, 118.15], p = 0.0003), 36 mg/day (OR 17.43, 95% CI [3.18, 95.66], p = 0.001) and 45 mg/day (OR 23.17, 95% CI [4.37, 123.03], p = 0.0002). Total but not severe adverse events were significantly higher with all the doses of orforglipron compared to placebo, with the hazard ratios being higher with higher doses. Gastrointestinal side‐effects were predominant side effects, being dose‐dependent, with nausea, vomiting, constipation, and gastroesophageal reflux being the predominant ones. Conclusion Orforglipron at 24–45 mg/day doses is an effective weight loss medication. The efficacy versus side effect profile suggests that 24–36 mg/day is the most optimal dose for orforglipron as an anti‐obesity medicine. Orforglipron at doses of 24–45 mg/day is an effective weight loss medication. 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B. M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Orforglipron, a novel non‐peptide oral daily glucagon‐like peptide‐1 receptor agonist as an anti‐obesity medicine: A systematic review and meta‐analysis</atitle><jtitle>Obesity science &amp; practice</jtitle><addtitle>Obes Sci Pract</addtitle><date>2024-04</date><risdate>2024</risdate><volume>10</volume><issue>2</issue><spage>e743</spage><epage>n/a</epage><pages>e743-n/a</pages><issn>2055-2238</issn><eissn>2055-2238</eissn><abstract>Background Orforglipron is a novel once‐daily oral non‐peptide glucagon‐like peptide‐1 receptor agonist with several recently published randomized controlled trials (RCTs) evaluating its role in diabetes and obesity. No meta‐analysis has analyzed the efficacy and safety of orforglipron; this meta‐analysis aimed to address this knowledge gap. Methods A systematic search was conducted in electronic databases to identify RCTs that included individuals with obesity who were administered orforglipron and compared to either a placebo or an active comparator. The primary outcome of interest was the percent change in body weight. Results From 12 initially screened articles, data from three RCTs involving 774 people were analyzed with a follow‐up duration of up to 36 weeks. Compared to placebo, patients receiving orforglipron 12 mg/day (mean difference (MD), MD −5.48%, 95% CI [−7.64, −3.33], p &lt; 0.01), 24 mg/day (MD −8.51%, 95% confidence interval (CI) [−9.88, −7.14], p &lt; 0.01), 36 mg/day (MD −8.84%, 95% CI [−11.68, −6.00], p &lt; 0.01) and 45 mg/day (MD −8.24%, 95% CI [−12.84, −3.63], p &lt; 0.01) had a significantly greater percent reduction in body weight. The percentage of patients being able to achieve &gt;15% weight loss from baseline was significantly higher with orforglipron 24 mg/day [Odds ratio (OR) 21.90 (95% CI [4.06, 118.15], p = 0.0003), 36 mg/day (OR 17.43, 95% CI [3.18, 95.66], p = 0.001) and 45 mg/day (OR 23.17, 95% CI [4.37, 123.03], p = 0.0002). Total but not severe adverse events were significantly higher with all the doses of orforglipron compared to placebo, with the hazard ratios being higher with higher doses. Gastrointestinal side‐effects were predominant side effects, being dose‐dependent, with nausea, vomiting, constipation, and gastroesophageal reflux being the predominant ones. Conclusion Orforglipron at 24–45 mg/day doses is an effective weight loss medication. The efficacy versus side effect profile suggests that 24–36 mg/day is the most optimal dose for orforglipron as an anti‐obesity medicine. Orforglipron at doses of 24–45 mg/day is an effective weight loss medication. The efficacy versus side effect profile suggests that 24–36 mg/day is the most optimal dose for orforglipron as an anti‐obesity medicine.</abstract><cop>United States</cop><pub>John Wiley &amp; Sons, Inc</pub><pmid>38414573</pmid><doi>10.1002/osp4.743</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0003-0249-2523</orcidid><orcidid>https://orcid.org/0000-0003-4915-8805</orcidid><orcidid>https://orcid.org/0000-0001-6865-5554</orcidid><orcidid>https://orcid.org/0000-0002-5681-6522</orcidid><oa>free_for_read</oa></addata></record>
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source Open Access: Wiley-Blackwell Open Access Journals; Publicly Available Content Database; PubMed Central
subjects Agonists
Bias
Blood pressure
Body mass index
Body weight loss
Clinical trials
Constipation
Diabetes
Diabetes mellitus
Drug dosages
emerging treatments
Gastroesophageal reflux
GLP1RA
Glucagon
Glucagon-like peptide 1
Hemoglobin
medications
Medicine
Meta-analysis
Obesity
orforglipron
Peptides
Placebos
Review
Side effects
Systematic review
Weight control
title Orforglipron, a novel non‐peptide oral daily glucagon‐like peptide‐1 receptor agonist as an anti‐obesity medicine: A systematic review and meta‐analysis
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