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[159.112.244.16]) by mx.google.com with UTF8SMTPS id af79cd13be357-8fc2938d649si143491985a.136.2026.05.01.04.34.38 for (version=TLS1_2 cipher=ECDHE-ECDSA-AES128-GCM-SHA256 bits=128/128); Fri, 01 May 2026 04:34:39 -0700 (PDT) Received-SPF: pass (google.com: domain of bounce+a6cce7.4d1858-tjphuhs=gmail.com@mg2.substack.com designates 159.112.244.16 as permitted sender) client-ip=159.112.244.16; Authentication-Results: mx.google.com; dkim=pass header.i=@mg2.substack.com header.s=mailo header.b=F4nW39Zj; dkim=pass header.i=@mailgun.org header.s=mg header.b="glg/tStt"; spf=pass (google.com: domain of bounce+a6cce7.4d1858-tjphuhs=gmail.com@mg2.substack.com designates 159.112.244.16 as permitted sender) smtp.mailfrom="bounce+a6cce7.4d1858-tjphuhs=gmail.com@mg2.substack.com"; dmarc=pass (p=REJECT sp=REJECT dis=NONE) header.from=substack.com DKIM-Signature: a=rsa-sha256; v=1; c=relaxed/relaxed; d=mg2.substack.com; q=dns/txt; s=mailo; t=1777635278; x=1777642478; h=List-Unsubscribe-Post: List-Unsubscribe: List-Post: List-Id: List-Archive: List-Owner: Reply-To: In-Reply-To: References: Sender: Sender: Date: Message-Id: To: To: From: From: Subject: Subject: Content-Type: Mime-Version: X-Feedback-Id; bh=clESN05Buhm0obQ3kWjCuUIDps+l4+zn0jHbFAgOmro=; b=F4nW39Zj8NH+zyLvPqU8z8JKtTXN5y3/c2eFtss/d0VOuDk7WmCFe9j97a2Po3X3IxfE3wYZF8l4zsMKFOfBqtMEJ8+Yq7EtiDZqnLz/MsLEFSBI2Ev4vPiuUnnqqUvXt7dJbCULMXlXZRXaJ8iyEUu5FHNB3mFnWHFD35cP2Y4= DKIM-Signature: a=rsa-sha256; v=1; c=relaxed/relaxed; d=mailgun.org; q=dns/txt; s=mg; t=1777635278; x=1777642478; h=List-Unsubscribe-Post: List-Unsubscribe: List-Post: List-Id: List-Archive: List-Owner: Reply-To: In-Reply-To: References: Sender: Sender: Date: Message-Id: To: To: From: From: Subject: Subject: Content-Type: Mime-Version: X-Feedback-Id; bh=clESN05Buhm0obQ3kWjCuUIDps+l4+zn0jHbFAgOmro=; b=glg/tSttDaQw87kt86hPU5zGwiXQ6EBUimFtVQQC9xivMcIGODUCHqgSVXNDO41d4CYlGaa32s3vsPsrDU87529r3e1z7Sztlxsu4JxGm3L8nbqpSqARZwZttIkOGLJXOVpVuivdhJ9Hix6mmV7TSqSTTv4birVTv8ky04iOgM0= X-Mailgun-Sid: WyIxODZiYSIsInRqcGh1aHNAZ21haWwuY29tIiwiNGQxODU4Il0= X-Feedback-Id: postmaster@mg2.substack.com:post:5a78b6d5cd16820001f2a9d4:mailgun Received: by ee0679e6303617a4875bf380fe96c12b233b6588cd977e1b5477f3ed4eeaae0d with HTTP id 69f48fced132fa749b855720; Fri, 01 May 2026 11:34:38 GMT X-Mailgun-Sending-Ip: 159.112.244.16 Mime-Version: 1.0 Content-Type: multipart/alternative; boundary="687fddab2cdd7d00beaa28e6530beb470cc4cb7e30d256e717e3b37c6de6" Subject: Semaglutide and Alcohol: A New Study in The Lancet is Worthy of Attention From: Dave Knapp from On The Pen To: tjphuhs@gmail.com X-Mailgun-Tag: post X-Mailgun-Track-Clicks: false Message-Id: <20260501113147.3.b534ca94b959b059@mg2.substack.com> Date: Fri, 1 May 2026 11:31:47 +0000 Feedback-Id: post-196059429:cat-post:pub-4808993:substack Sender: Dave Knapp from On The Pen References: In-Reply-To: Reply-To: Dave Knapp from On The Pen List-Owner: List-Url: List-Archive: List-Id: List-Post: List-Unsubscribe: List-Unsubscribe-Post: List-Unsubscribe=One-Click X-Mailgun-Variables: {"category": "post", "email_generated_at": "1777635278300", "is_freemail": "true", "post_audience": "everyone", "post_id": "196059429", "post_type": "newsletter", "pub_community_enabled": "true", "publication_id": "4808993", "subdomain": "onthepen", "user_id": "273622398"} --687fddab2cdd7d00beaa28e6530beb470cc4cb7e30d256e717e3b37c6de6 Content-Type: text/plain; charset="utf-8" Content-Transfer-Encoding: quoted-printable View this post on the web at https://onthepen.substack.com/p/semaglutide-an= d-alcohol-a-new-study There=E2=80=99s a particular kind of exhaustion that comes with alcohol use= disorder. Not just the physical kind, though that=E2=80=99s real too. I=E2= =80=99m talking the kind that settles into your bones after years of trying= , having minimal success, and trying again. After being told, in ways spoke= n and unspoken, that the problem was really just a lack of willpower. That = if you really wanted it badly enough, you=E2=80=99d find your way out event= ually. Sound familiar? If you=E2=80=99ve lived inside the obesity fight, you know this cycle all t= oo well. The same cycle of white knuckle effort and utter disappointment. T= he same medical shrug. The same story that put the weight of a biological c= ondition squarely on the shoulders of the person carrying it. Two different= diagnoses. The same long loneliness. This week, the condition that has bee= n waiting even longer for a real pharmacological answer got some news. And = the drug at the center of it is one you already well know. Researchers in Copenhagen just published a randomized controlled trial in T= he Lancet [ https://substack.com/redirect/f4aaa0dd-0168-4075-ac83-a84505495= 628?j=3DeyJ1IjoiNGl3b2U2In0.sVDxRtmZ85v8kfdamY0krRXGMy3p768BWtuZifRB-Zs ], = one of the most respected medical journals in the world, testing whether se= maglutide, the active ingredient in Wegovy and Ozempic, could reduce heavy = drinking in people with alcohol use disorder. The results were clear enough= that they=E2=80=99ll be difficult for the medical community to set aside. = People in the study who received weekly semaglutide injections reduced thei= r heavy drinking days by 41% over six months. People who received a placebo= , a salt water injection, reduced theirs by 26%. That gap, roughly 14 perce= ntage points, is statistically robust and clinically meaningful. Semaglutid= e didn=E2=80=99t just help a little. It helped in a way that showed up clea= rly against a control group that was also receiving therapy and weekly chec= k-ins, conditions that already tend to move the needle on their own. In the= obesity world, we call those =E2=80=9Clifestyle modifications=E2=80=9D. The trial enrolled 108 people, split evenly between the drug and placebo. E= veryone received cognitive behavioral therapy across the 26 weeks. By the e= nd, the people on semaglutide were not only having fewer heavy drinking day= s. They were also drinking less per drinking day, reporting significantly l= ess craving, showing improved liver enzyme numbers, and losing considerably= more weight than the placebo group. For decades, the FDA has approved exactly three medications for alcohol use= disorder: disulfiram, acamprosate, and naltrexone. Three medications for a= condition that accounts for 5% of deaths worldwide every year. Those medic= ations help some people, and that certainly matters. It matters in the same= way that phentermine and orlistat mattered to obesity. A useful way to thi= nk about how well a treatment works is something called the number needed t= o treat, which captures how many people have to take the drug for one perso= n to meaningfully benefit. For the existing approved medications, that numb= er sits at 7 or higher. For semaglutide in this trial, it was 4.3. That gap= represents real people, and real outcomes that currently aren=E2=80=99t ha= ppening for them. What makes this study harder to dismiss than a self-reported survey alone i= s that the researchers also measured a blood biomarker called phosphatidyle= thanol, which reflects actual alcohol intake independent of what people say= =2E Drinking diaries and questionnaires= are useful, but they carry the weight= of memory and motivation. The biomarker confirmed what the self-reports sh= owed, and that convergence matters. When two different kinds of evidence po= int in the same direction, the signal gets stronger. This study enrolled people who were obese, BMI of 30 or above, because prio= r research suggested GLP-1 medications might work better in that population= =2E That means we don=E2=80=99t yet know w= hether the same effect holds for pe= ople with AUD who aren=E2=80=99t carrying extra weight, and that=E2=80=99s = a meaningful gap given how many people live with alcohol use disorder acros= s a wide range of body types. The trial also ran only 26 weeks, with no fol= low-up data collected after it ended, so there=E2=80=99s no way to know yet= whether the gains hold a year out, or what happens when someone stops the = drug. Side effects were real and worth naming honestly. More than half of t= he people on semaglutide experienced nausea, along with constipation, reflu= x, and fatigue at higher rates than the placebo group. Most of those effect= s were temporary and mild to moderate, but this is not a medication that as= ks nothing of your body. And it bears repeating that this was one trial, 10= 8 people, in one city in Denmark, with a study population that was predomin= antly White. The researchers themselves are careful to say that larger, mor= e diverse studies are needed before anyone should consider using this drug = off-label for AUD. This is just the beginning. Eli Lilly has a dual GLP-1/GIP co-agonist calle= d brenipatide that is being looked at for a whole host of nueralogical diso= rders. A large phase 3 trial with a potential submission for approval and a= n actual indication will begin this year. The incretin class of medications= are serving up hope to many people fighting various addictions.=20 There are an estimated 8 million Americans living with both obesity and pro= blematic alcohol use. For them, a drug already prescribed and in many cases= covered for weight loss may be doing something else quietly. Despite sever= al years of anecdotal evidience, science is now meaningfully catching up to= the potential benefits of these medications. For the broader population of= people with AUD, this study adds meaningful weight to a growing body of ev= idence that GLP-1 receptor agonists deserve serious investigation as a trea= tment for addiction, not just metabolism. The door has been stuck for a ver= y long time. This research doesn=E2=80=99t fling it open, but it moves it. = And for people who have been pushing on it for years, that is not nothing. Unsubscribe https://substack.com/redirect/2/eyJlIjoiaHR0cHM6Ly9vbnRoZXBlbi5= zdWJzdGFjay5jb20vYWN0aW9uL2Rpc2FibGVfZW1haWw_dG9rZW49ZXlKMWMyVnlYMmxrSWpveU= 56TTJNakl6T1Rnc0luQnZjM1JmYVdRaU9qRTVOakExT1RReU9Td2lhV0YwSWpveE56YzNOak0xT= WpjNExDSmxlSEFpT2pFNE1Ea3hOekV5Tnpnc0ltbHpjeUk2SW5CMVlpMDBPREE0T1Rreklpd2lj= M1ZpSWpvaVpHbHpZV0pzWlY5bGJXRnBiQ0o5LnFpYkVfR2xEOWpldVBOR2ZuUXV5LUoteEJhZmh= VZlgyeXZiQUhfU3FvRTAiLCJwIjoxOTYwNTk0MjksInMiOjQ4MDg5OTMsImYiOnRydWUsInUiOj= I3MzYyMjM5OCwiaWF0IjoxNzc3NjM1Mjc4LCJleHAiOjIwOTMyMTEyNzgsImlzcyI6InB1Yi0wI= iwic3ViIjoibGluay1yZWRpcmVjdCJ9.Ktxz34FJmQEswwwpw2kbBUb_wmkU-rrzSYq8pUnRuv4= ? --687fddab2cdd7d00beaa28e6530beb470cc4cb7e30d256e717e3b37c6de6 Content-Type: text/html; charset="utf-8" Content-Transfer-Encoding: quoted-printable = Semaglutide and Alcohol: A New Study in The Lancet is Worthy of Attention</= title><style> @media (max-width: 1024px) { .typography .pullquote-align-left, .typography.editor .pullquote-align-left, .typography .pullquote-align-right, 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8px; top: 45px; } } @media not all and (min-resolution: 0.001dpcm) { @supports (-webkit-appearance: none) { p a:not(.primary.button), .post p:not(.button-wrapper) a:not(.primary.button), .footnote a.footnote-anchor:not(.primary.button), .thread-head .markup p:not(.button-wrapper) a:not(.primary.button) { color: #f34dc9; text-decoration: none; } p a:not(.primary.button):hover, .post p:not(.button-wrapper) a:not(.primary.button):hover, .footnote a.footnote-anchor:not(.primary.button):hover, .thread-head .markup p:not(.button-wrapper) a:not(.primary.button):hove= r { text-decoration: underline; } } }</style></head><body class=3D"email-body" style=3D"font-kerning: auto;--im= age-offset-margin: -120px;"><img src=3D"https://eotrx.substackcdn.com/o/8f4= deb9086e88513/p.gif?token=3DeyJtIjoiPDIwMjYwNTAxMTEzMTQ3LjMuYjUzNGNhOTRiOTU= 5YjA1OUBtZzIuc3Vic3RhY2suY29tPiIsInUiOjI3MzYyMjM5OCwiciI6InRqcGh1aHNAZ21haW= wuY29tIiwiZCI6Im1nMi5zdWJzdGFjay5jb20iLCJwIjoxOTYwNTk0MjksInQiOiJuZXdzbGV0d= GVyIiwiYSI6ImV2ZXJ5b25lIiwicyI6NDgwODk5MywiYyI6InBvc3QiLCJmIjp0cnVlLCJwb3Np= dGlvbiI6InRvcCIsImlhdCI6MTc3NzYzNTI3OCwiZXhwIjoxNzgwMjI3Mjc4LCJpc3MiOiJwdWI= tMCIsInN1YiI6ImVvIn0.KUOEUOGZLQ-bJEnK27ESM3YMZjwOHGibR0XsqYE2IO0" alt=3D"" = width=3D"1" height=3D"1" border=3D"0" style=3D"height:1px !important;width:= 1px !important;border-width:0 !important;margin-top:0 !important;margin-bot= tom:0 !important;margin-right:0 !important;margin-left:0 !important;padding= -top:0 !important;padding-bottom:0 !important;padding-right:0 !important;pa= dding-left:0 !important;"/><div class=3D"preview" style=3D"display:none;fon= t-size:1px;color:#333333;line-height:1px;max-height:0px;max-width:0px;opaci= ty:0;overflow:hidden;">Anecdotes are slowly becoming science</div><div clas= s=3D"preview" style=3D"display:none;font-size:1px;color:#333333;line-height= :1px;max-height:0px;max-width:0px;opacity:0;overflow:hidden;">͏  =   ­͏     ­͏     ­T= 7;     ­͏     ­͏     &= #173;͏     ­͏     ­͏   =   ­͏     ­͏     ­͏= ;     ­͏     ­͏     &#= 173;͏     ­͏     ­͏   &= #8199; ­͏     ­͏     ­͏=     ­͏     ­͏     = 73;͏     ­͏     ­͏   &#= 8199; ­͏     ­͏     ­͏ =     ­͏     ­͏     = 3;͏     ­͏     ­͏   = 199; ­͏     ­͏     ­͏ &= nbsp;   ­͏     ­͏     ­= ;͏     ­͏     ­͏   Q= 99; ­͏     ­͏     ­͏ &n= bsp;   ­͏     ­͏     ­= ͏     ­͏     ­͏   ̳= 9; ­͏     ­͏     ­͏ &nb= sp;   ­͏     ­͏     ­&= #847;     ­͏     ­͏    = ; ­͏     ­͏     ­͏ &nbs= p;   ­͏     ­͏     ­&#= 847;     ­͏     ­͏    = ­͏     ­͏     ­͏  = ;   ­͏     ­͏     ­= 47;     ­͏     ­͏     = ­͏     ­͏     ­͏  =   ­͏     ­͏     ­T= 7;     ­͏     ­͏     &= #173;͏     ­͏     ­͏   =   ­͏     ­͏     ­͏= ;     ­͏     ­͏     &#= 173;͏     ­͏     ­͏   &= #8199; ­͏     ­͏     ­͏=     ­͏     ­͏     = 73;͏     ­͏     ­͏   &#= 8199; ­͏     ­͏     ­͏ =     ­͏     ­͏     = 3;͏     ­͏     ­͏   = 199; ­͏     ­͏     ­͏ &= nbsp;   ­͏     ­͏     ­= ;͏     ­͏     ­͏   Q= 99; ­͏     ­͏     ­͏ &n= bsp;   ­͏     ­͏     ­= ͏     ­͏     ­͏   ̳= 9; ­͏     ­͏     ­͏ &nb= sp;   ­͏     ­͏     ­&= #847;     ­͏     ­͏    = ; ­͏     ­͏     ­͏ &nbs= p;   ­͏     ­͏     ­&#= 847;     ­͏     ­͏    = ­͏     ­͏     ­͏  = ;   ­͏     ­͏     ­= 47;     ­͏     ­͏     = ­͏     ­͏     ­͏  =   ­͏     ­͏     ­T= 7;     ­͏     ­͏     &= #173;͏     ­͏     ­͏   =   ­͏     ­͏     ­͏= ;     ­͏     ­͏     &#= 173;͏     ­͏     ­͏   &= #8199; ­͏     ­͏     ­͏=     ­͏     ­͏     = 73;͏     ­͏     ­͏   &#= 8199; ­͏     ­͏     ­͏ =     ­͏     ­͏     = 3;͏     ­͏     ­͏   = 199; ­͏     ­͏     ­͏ &= nbsp;   ­͏     ­͏     ­= ;͏     ­͏     ­͏   Q= 99; ­͏     ­͏     ­͏ &n= bsp;   ­͏     ­͏     ­= ͏     ­͏     ­͏   ̳= 9; ­͏     ­</div><table class=3D"email-body-conta= iner" role=3D"presentation" width=3D"100%" border=3D"0" cellspacing=3D"0" c= ellpadding=3D"0"><tbody><tr><td></td><td class=3D"content" width=3D"550"></= td><td></td></tr><tr><td></td><td class=3D"content" width=3D"550" align=3D"= left"><div style=3D"font-size: 16px;line-height: 26px;max-width: 550px;widt= h: 100%;margin: 0 auto;overflow-wrap: break-word;"><table role=3D"presentat= ion" width=3D"100%" border=3D"0" cellspacing=3D"0" cellpadding=3D"0"><tbody= ><tr><td align=3D"right" style=3D"height:20px;"><table role=3D"presentation= " width=3D"auto" border=3D"0" cellspacing=3D"0" cellpadding=3D"0"><tbody><t= r><td style=3D"vertical-align:middle;"><span class=3D"pencraft pc-reset res= et-IxiVJZ tw-font-body tw-text-ssm tw-text-substack-secondary" style=3D"fon= t-family: SF Pro Text, -apple-system, system-ui, BlinkMacSystemFont, Inter,= Segoe UI, Roboto, Helvetica, Arial, sans-serif, Apple Color Emoji, Segoe U= I Emoji, Segoe UI Symbol;font-size: 13px;color: unset;list-style: none;text= -decoration: unset;margin: 0;"><div class=3D"pencraft pc-reset align-right-= VJbKw5 size-12-mmZ61m reset-IxiVJZ" style=3D"list-style: none;color: unset;= text-align: right;font-size: 12px;line-height: 16px;text-decoration: unset;= margin: 0;"><span class=3D"pencraft pc-reset reset-IxiVJZ" translated=3D"" = 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M2MjIzOTgsInBvc3RfaWQiOjE5NjA1OTQyOSwiaWF0IjoxNzc3NjM1Mjc4LCJleHAiOjE3ODAyM= jcyNzgsImlzcyI6InB1Yi00ODA4OTkzIiwic3ViIjoicG9zdC1yZWFjdGlvbiJ9.B6nHOSzBX7i= X5kn1FPJdK3X3E5GEeV2DCfrBrWPo9H4" style=3D"color: rgb(54,55,55);text-decora= tion: none;">Semaglutide and Alcohol: A New Study in The Lancet is Worthy o= f Attention</a></h1><h3 class=3D"subtitle subtitle-HEEcLo" dir=3D"auto" sty= le=3D"direction: auto;text-align: start;unicode-bidi: isolate;font-family: = 'SF Pro Display',-apple-system-headline,system-ui,-apple-system,BlinkMacSys= temFont,'Segoe UI',Roboto,Helvetica,Arial,sans-serif,'Apple Color Emoji','S= egoe UI Emoji','Segoe UI Symbol';font-weight: normal;-webkit-font-smoothing= : antialiased;-moz-osx-font-smoothing: antialiased;-webkit-appearance: opti= mizelegibility;-moz-appearance: optimizelegibility;appearance: optimizelegi= bility;margin: 4px 0 0;color: #777777;line-height: 24px;font-size: 18px;mar= gin-top: 12px;">Anecdotes are slowly becoming science</h3><table class=3D"p= 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":null,"title":null,"type":"image/png",&= quot;href":null,"belowTheFold":false,"topImage":tr= ue,"internalRedirect":"https://onthepen.substack.com/i/19605= 9429?img=3Dhttps%3A%2F%2Fsubstack-post-media.s3.amazonaws.com%2Fpublic%2Fim= ages%2F09265cec-b63b-404c-8fb7-4f7f773b9530_1536x1024.png","isPro= cessing":false,"align":null,"offset":false}" alt= =3D"" width=3D"550" height=3D"366.7925824175824" src=3D"https://substackcdn= =2Ecom/image/fetch/$s_!ZYG-!,w_1100,c_l= imit,f_auto,q_auto:good,fl_progressive= :steep/https%3A%2F%2Fsubstack-post-media.s3.amazonaws.com%2Fpublic%2Fimages= %2F09265cec-b63b-404c-8fb7-4f7f773b9530_1536x1024.png" style=3D"border: non= e !important;vertical-align: middle;display: block;-ms-interpolation-mode: = bicubic;height: auto;margin-bottom: 0;width: auto !important;max-width: 100= % !important;margin: 0 auto;"></a></td><td style=3D"text-align: center;"></= td></tr></tbody></table></figure></div><p style=3D"margin: 0 0 20px 0;color= : rgb(54,55,55);line-height: 26px;font-size: 16px;">There’s a particu= lar kind of exhaustion that comes with alcohol use disorder. Not just the p= hysical kind, though that’s real too. I’m talking the kind that= settles into your bones after years of trying, having minimal success, and= trying again. After being told, in ways spoken and unspoken, that the prob= lem was really just a lack of willpower. That if you really wanted it badly= enough, you’d find your way out eventually. Sound familiar?</p><p st= yle=3D"margin: 0 0 20px 0;color: rgb(54,55,55);line-height: 26px;font-size:= 16px;">If you’ve lived inside the obesity fight, you know this cycle= all too well. The same cycle of white knuckle effort and utter disappointm= ent. The same medical shrug. The same story that put the weight of a biolog= ical condition squarely on the shoulders of the person carrying it. Two dif= ferent diagnoses. The same long loneliness. This week, the condition that h= as been waiting even longer for a real pharmacological answer got some news= =2E And the drug at the center of it is= one you already well know.</p><p styl= e=3D"margin: 0 0 20px 0;color: rgb(54,55,55);line-height: 26px;font-size: 1= 6px;"><span>Researchers in Copenhagen just published a randomized controlle= d trial in </span><a href=3D"https://substack.com/redirect/f4aaa0dd-0168-40= 75-ac83-a84505495628?j=3DeyJ1IjoiNGl3b2U2In0.sVDxRtmZ85v8kfdamY0krRXGMy3p76= 8BWtuZifRB-Zs" style=3D"color: #f34dc9;text-decoration: none;">The Lancet</= a><span>, one of the most respected medical journals in the world, testing = whether semaglutide, the active ingredient in Wegovy and Ozempic, could red= uce heavy drinking in people with alcohol use disorder. The results were cl= ear enough that they’ll be difficult for the medical community to set= aside. People in the study who received weekly semaglutide injections redu= ced their heavy drinking days by 41% over six months. People who received a= placebo, a salt water injection, reduced theirs by 26%. That gap, roughly = 14 percentage points, is statistically robust and clinically meaningful. Se= maglutide didn’t just help a little. It helped in a way that showed u= p clearly against a control group that was also receiving therapy and weekl= y check-ins, conditions that already tend to move the needle on their own. = In the obesity world, we call those “lifestyle modifications”.<= /span></p><table class=3D"static-file-embed-table" cellspacing=3D"16" data-= component-name=3D"FileToDOMStatic" style=3D"width: 100%;z-index: 5;margin-b= ottom: 1rem;border: 1px solid rgb(0,0,0,.1);background-color: rgb(255,255,2= 55);border-radius: 8px;"><tbody><tr><td class=3D"static-file-embed-thumbnai= l-container default" style=3D"position: relative;min-width: 74px;max-width:= 74px;width: 74px;height: 74px;"><img class=3D"static-file-embed-thumbnail = default" src=3D"https://substackcdn.com/image/fetch/$s_!0Cy0!,w_32,h_32,c_f= ill,f_auto,q_auto:good,fl_progressive:steep,g_auto/https%3A%2F%2Fsubstack.c= om%2Fimg%2Fattachment_icon.svg" style=3D"width: 100px !important;border: no= ne !important;vertical-align: middle;max-width: 42px !important;max-height:= 42px !important;display: block;-ms-interpolation-mode: bicubic;height: aut= o;margin: 0 auto;"></td><td class=3D"static-file-embed-details default" sty= le=3D"width: 100%;position: relative;vertical-align: center;min-height: 37p= x;height: 37px;"><div class=3D"static-file-embed-details-h1" style=3D"font-= family: 'SF Pro Display', -apple-system, system-ui, BlinkMacSystemFont, 'In= ter', 'Segoe UI', Roboto, Helvetica, Arial, sans-serif, 'Apple Color Emoji'= , 'Segoe UI Emoji', 'Segoe UI Symbol';-webkit-font-smoothing: antialiased;-= moz-osx-font-smoothing: antialiased;-webkit-appearance: optimizelegibility;= -moz-appearance: optimizelegibility;appearance: optimizelegibility;letter-s= pacing: -0.012em;font-style: normal;font-weight: 600;font-size: 16px;line-h= eight: 26px;">Lancet Study: Semaglutide vs Pacebo for ...</div><div class= =3D"static-file-embed-details-h2" style=3D"font-family: 'SF Pro Display', -= apple-system, system-ui, BlinkMacSystemFont, 'Inter', 'Segoe UI', Roboto, H= elvetica, Arial, sans-serif, 'Apple Color Emoji', 'Segoe UI Emoji', 'Segoe = UI Symbol';-webkit-font-smoothing: antialiased;-moz-osx-font-smoothing: ant= ialiased;-webkit-appearance: optimizelegibility;-moz-appearance: optimizele= gibility;appearance: optimizelegibility;letter-spacing: -0.012em;font-style= : normal;font-weight: normal;color: rgb(119,119,119);font-size: 16px;line-h= eight: 26px;">954KB ∙ PDF file</div></td></tr><tr><td class=3D"static= -file-embed-button-container" colspan=3D"2" style=3D"text-decoration: none;= width: 100%;"><table class=3D"static-file-embed-button" cellspacing=3D"0" s= tyle=3D"width: 100%;vertical-align: center;text-align: center;font-family: = 'SF Pro Display', -apple-system, system-ui, BlinkMacSystemFont, 'Inter', 'S= egoe UI', Roboto, Helvetica, Arial, sans-serif, 'Apple Color Emoji', 'Segoe= UI Emoji', 'Segoe UI Symbol';-webkit-font-smoothing: antialiased;-moz-osx-= font-smoothing: antialiased;-webkit-appearance: optimizelegibility;-moz-app= earance: optimizelegibility;appearance: optimizelegibility;letter-spacing: = -0.012em;font-style: normal;font-weight: 600;font-size: 16px;"><tbody><tr><= td align=3D"center"><a class=3D"static-file-embed-anchor" href=3D"https://s= ubstack.com/redirect/ff5c6244-4e9a-459b-9a75-5f263fa5d532?j=3DeyJ1IjoiNGl3b= 2U2In0.sVDxRtmZ85v8kfdamY0krRXGMy3p768BWtuZifRB-Zs" style=3D"text-decoratio= n: none !important;background-color: rgb(238,238,238);border: 1px solid rgb= (0,0,0,.1);color: rgb(119,119,119);height: 20px;width: 100%;display: inline= -block;border-radius: 8px;line-height: 20px;padding-top: 20px;padding-botto= m: 20px;">Download</a></td></tr></tbody></table></td></tr></tbody></table><= p style=3D"margin: 0 0 20px 0;color: rgb(54,55,55);line-height: 26px;font-s= ize: 16px;">The trial enrolled 108 people, split evenly between the drug an= d placebo. Everyone received cognitive behavioral therapy across the 26 wee= ks. By the end, the people on semaglutide were not only having fewer heavy = drinking days. They were also drinking less per drinking day, reporting sig= nificantly less craving, showing improved liver enzyme numbers, and losing = considerably more weight than the placebo group.</p><p style=3D"margin: 0 0= 20px 0;color: rgb(54,55,55);line-height: 26px;font-size: 16px;">For decade= s, the FDA has approved exactly three medications for alcohol use disorder:= disulfiram, acamprosate, and naltrexone. Three medications for a condition= that accounts for 5% of deaths worldwide every year. Those medications hel= p some people, and that certainly matters. It matters in the same way that = phentermine and orlistat mattered to obesity. A useful way to think about h= ow well a treatment works is something called the number needed to treat, w= hich captures how many people have to take the drug for one person to meani= ngfully benefit. For the existing approved medications, that number sits at= 7 or higher. For semaglutide in this trial, it was 4.3. That gap represent= s real people, and real outcomes that currently aren’t happening for = them.</p><p style=3D"margin: 0 0 20px 0;color: rgb(54,55,55);line-height: 2= 6px;font-size: 16px;">What makes this study harder to dismiss than a self-r= eported survey alone is that the researchers also measured a blood biomarke= r called phosphatidylethanol, which reflects actual alcohol intake independ= ent of what people say. Drinking diaries and questionnaires are useful, but= they carry the weight of memory and motivation. The biomarker confirmed wh= at the self-reports showed, and that convergence matters. When two differen= t kinds of evidence point in the same direction, the signal gets stronger.<= /p><p style=3D"margin: 0 0 20px 0;color: rgb(54,55,55);line-height: 26px;fo= nt-size: 16px;">This study enrolled people who were obese, BMI of 30 or abo= ve, because prior research suggested GLP-1 medications might work better in= that population. That means we don’t yet know whether the same effec= t holds for people with AUD who aren’t carrying extra weight, and tha= t’s a meaningful gap given how many people live with alcohol use diso= rder across a wide range of body types. The trial also ran only 26 weeks, w= ith no follow-up data collected after it ended, so there’s no way to = know yet whether the gains hold a year out, or what happens when someone st= ops the drug. Side effects were real and worth naming honestly. More than h= alf of the people on semaglutide experienced nausea, along with constipatio= n, reflux, and fatigue at higher rates than the placebo group. Most of thos= e effects were temporary and mild to moderate, but this is not a medication= that asks nothing of your body. And it bears repeating that this was one t= rial, 108 people, in one city in Denmark, with a study population that was = predominantly White. The researchers themselves are careful to say that lar= ger, more diverse studies are needed before anyone should consider using th= is drug off-label for AUD.</p><div class=3D"subscribe-widget is-signed-up" = data-component-name=3D"SubscribeWidget" style=3D"margin: 0 0 1em;direction:= ltr;font-size: 16px;line-height: 26px;"><div class=3D"pencraft pc-reset bu= tton-wrapper" style=3D"text-decoration: unset;list-style: none;font-size: 1= 6px;line-height: 26px;text-align: center;cursor: pointer;border-radius: 4px= ;"><a class=3D"button subscribe-btn primary" href=3D"https://substack.com/r= edirect/2/eyJlIjoiaHR0cHM6Ly9vbnRoZXBlbi5zdWJzdGFjay5jb20vc3Vic2NyaWJlP3V0b= V9zb3VyY2U9cG9zdCZ1dG1fY2FtcGFpZ249ZW1haWwtY2hlY2tvdXQmbmV4dD1odHRwcyUzQSUy= RiUyRm9udGhlcGVuLnN1YnN0YWNrLmNvbSUyRnAlMkZzZW1hZ2x1dGlkZS1hbmQtYWxjb2hvbC1= hLW5ldy1zdHVkeSZyPTRpd29lNiZ0b2tlbj1leUoxYzJWeVgybGtJam95TnpNMk1qSXpPVGdzSW= 1saGRDSTZNVGMzTnpZek5USTNPQ3dpWlhod0lqb3hOemd3TWpJM01qYzRMQ0pwYzNNaU9pSndkV= 0l0TkRnd09EazVNeUlzSW5OMVlpSTZJbU5vWldOcmIzVjBJbjAuYWJfOE4tcWJWMXhLS3A3OThQ= Y0tJc0pqNVY1X2trekNiT2UzdUNZcDNzVSIsInAiOjE5NjA1OTQyOSwicyI6NDgwODk5MywiZiI= 6dHJ1ZSwidSI6MjczNjIyMzk4LCJpYXQiOjE3Nzc2MzUyNzgsImV4cCI6MjA5MzIxMTI3OCwiaX= NzIjoicHViLTAiLCJzdWIiOiJsaW5rLXJlZGlyZWN0In0._CI-0RqKMN6scGgrzuOZtKFsKjriQ= msXIAFSfg7_cVQ?&utm_medium=3Demail&utm_source=3Dsubscribe-widget&utm_conten= t=3D196059429" style=3D"font-family: system-ui,-apple-system,BlinkMacSystem= Font,'Segoe UI',Roboto,Helvetica,Arial,sans-serif,'Apple Color Emoji','Sego= e UI Emoji','Segoe UI Symbol';display: inline-block;box-sizing: border-box;= cursor: pointer;border: none;border-radius: 8px;font-size: 14px;line-height= : 20px;font-weight: 600;text-align: center;opacity: 1;outline: none;white-s= pace: nowrap;text-decoration: none !important;margin: 0 auto;background-col= or: #f34dc9;color: #ffffff !important;padding: 12px 20px;height: auto;"><sp= an style=3D"color: #ffffff;text-decoration: none;">Upgrade to paid</span></= a></div></div><p style=3D"margin: 0 0 20px 0;color: rgb(54,55,55);line-heig= ht: 26px;font-size: 16px;">This is just the beginning. Eli Lilly has a dual= GLP-1/GIP co-agonist called brenipatide that is being looked at for a whol= e host of nueralogical disorders. A large phase 3 trial with a potential su= bmission for approval and an actual indication will begin this year. The in= cretin class of medications are serving up hope to many people fighting var= ious addictions. </p><p style=3D"margin: 0 0 20px 0;color: rgb(54,55,55);li= ne-height: 26px;font-size: 16px;margin-bottom: 0;">There are an estimated 8= million Americans living with both obesity and problematic alcohol use. Fo= r them, a drug already prescribed and in many cases covered for weight loss= may be doing something else quietly. Despite several years of anecdotal ev= idience, science is now meaningfully catching up to the potential benefits = of these medications. For the broader population of people with AUD, this s= tudy adds meaningful weight to a growing body of evidence that GLP-1 recept= or agonists deserve serious investigation as a treatment for addiction, not= just metabolism. The door has been stuck for a very long time. This resear= ch doesn’t fling it open, but it moves it. And for people who have be= en pushing on it for years, that is not nothing.</p></div></div><div class= =3D"container-border" style=3D"margin: 32px 0 0;width: 100%;box-sizing: bor= der-box;border-top: 1px solid #e6e6e6;font-size: 16px;line-height: 26px;"><= /div><div class=3D"typography" style=3D"--image-offset-margin: -120px;font-= size: 16px;line-height: 26px;"><div class=3D"postscript" style=3D"margin: 3= 2px 0;font-size: 16px;line-height: 26px;"><div class=3D"body markup" dir=3D= "auto" style=3D"text-align: initial;font-size: 16px;line-height: 26px;width= : 100%;word-break: break-word;margin-bottom: 16px;"><h2 class=3D"header-anc= hor-post" style=3D"position: relative;font-family: 'SF Pro Display',-apple-= system-headline,system-ui,-apple-system,BlinkMacSystemFont,'Segoe UI',Robot= o,Helvetica,Arial,sans-serif,'Apple Color Emoji','Segoe UI Emoji','Segoe UI= Symbol';font-weight: bold;-webkit-font-smoothing: antialiased;-moz-osx-fon= t-smoothing: antialiased;-webkit-appearance: 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