diff --git a/domains/health/glp1-receptor-agonists-address-substance-use-disorders-through-mesolimbic-dopamine-modulation.md b/domains/health/glp1-receptor-agonists-address-substance-use-disorders-through-mesolimbic-dopamine-modulation.md index 493aec190..d405b203f 100644 --- a/domains/health/glp1-receptor-agonists-address-substance-use-disorders-through-mesolimbic-dopamine-modulation.md +++ b/domains/health/glp1-receptor-agonists-address-substance-use-disorders-through-mesolimbic-dopamine-modulation.md @@ -60,3 +60,10 @@ Qeadan et al. (2025) retrospective cohort study of 1.3M patients across 136 US h **Source:** Grigson PS et al., Addiction Science & Clinical Practice 2025 NCT06548490 is the first Phase 2 RCT testing semaglutide for treatment-refractory OUD (n=200, patients already on buprenorphine/methadone who continue illicit use). Trial enrolled first participant January 2025, expected completion November 2026. Protocol formally published in Addiction Science & Clinical Practice (May 2025, PMID 40502777). This represents the definitive human trial that will either confirm or refute the animal/observational signal for OUD, extending the mechanism from AUD to opioid use disorders. + + +## Supporting Evidence + +**Source:** Hendershot et al., JAMA Psychiatry 2025 + +First RCT evidence: 26-week trial of 108 AUD+obesity patients showed semaglutide+CBT reduced heavy drinking days 41.1%, with NNT 4.3 versus 7+ for approved AUD medications. Blood-alcohol biomarkers corroborated self-reports. However, a separate cohort study found 195% increased MDD risk with GLP-1 agonists, requiring psychiatric screening. diff --git a/domains/health/glp1-receptor-agonists-demonstrate-superior-efficacy-for-alcohol-use-disorder-in-comorbid-obesity-population.md b/domains/health/glp1-receptor-agonists-demonstrate-superior-efficacy-for-alcohol-use-disorder-in-comorbid-obesity-population.md new file mode 100644 index 000000000..98ed8040b --- /dev/null +++ b/domains/health/glp1-receptor-agonists-demonstrate-superior-efficacy-for-alcohol-use-disorder-in-comorbid-obesity-population.md @@ -0,0 +1,20 @@ +--- +type: claim +domain: health +description: "Semaglutide plus CBT reduced heavy drinking days 41.1% in RCT, achieving NNT 4.3 versus 7+ for naltrexone and acamprosate, but limited to AUD patients with obesity comorbidity" +confidence: experimental +source: Hendershot et al., JAMA Psychiatry 2025; NIH press release April 2026 +created: 2026-05-02 +title: GLP-1 receptor agonists demonstrate NNT 4.3 for alcohol use disorder in adults with comorbid obesity — superior to all approved AUD medications +agent: vida +sourced_from: health/2026-04-xx-nih-jama-psychiatry-glp1-cbt-alcohol-use-disorder-rct.md +scope: causal +sourcer: NIH / JAMA Psychiatry +supports: ["glp1-receptor-agonists-address-substance-use-disorders-through-mesolimbic-dopamine-modulation"] +challenges: ["the mental health supply gap is widening not closing because demand outpaces workforce growth and technology primarily serves the already-served rather than expanding access"] +related: ["glp1-receptor-agonists-address-substance-use-disorders-through-mesolimbic-dopamine-modulation", "semaglutide-produces-large-effect-aud-reduction-through-vta-dopamine-suppression"] +--- + +# GLP-1 receptor agonists demonstrate NNT 4.3 for alcohol use disorder in adults with comorbid obesity — superior to all approved AUD medications + +A 26-week randomized, double-blind, placebo-controlled trial of 108 patients with both alcohol use disorder and obesity found that weekly semaglutide plus standard cognitive behavioral therapy produced a 41.1% reduction in heavy drinking days, with 13.7% greater improvement than placebo. The number needed to treat (NNT) was 4.3 — meaning approximately 4-5 patients need treatment to prevent one heavy drinking day. This represents a substantial improvement over approved AUD medications: naltrexone and acamprosate have NNTs of 7 or higher. Blood-alcohol biomarkers corroborated self-reported data, addressing a common validity concern in addiction research. The mechanism is hypothesized to involve GLP-1 receptor modulation of mesolimbic dopamine pathways, reducing the hedonic value of alcohol similar to how it reduces food craving. However, this finding is limited to the studied population: adults with comorbid AUD and obesity, which represents approximately 40% of AUD patients. A separate community-based cohort study found 195% increased risk of major depressive disorder among individuals treated with liraglutide or semaglutide, though this observational finding may be confounded by indication (obese/metabolically ill patients have higher baseline depression rates). Phase 3 trials are now underway to determine whether this efficacy translates to broader AUD populations and whether the depression risk signal is causal. diff --git a/inbox/queue/2026-04-xx-nih-jama-psychiatry-glp1-cbt-alcohol-use-disorder-rct.md b/inbox/archive/health/2026-04-xx-nih-jama-psychiatry-glp1-cbt-alcohol-use-disorder-rct.md similarity index 98% rename from inbox/queue/2026-04-xx-nih-jama-psychiatry-glp1-cbt-alcohol-use-disorder-rct.md rename to inbox/archive/health/2026-04-xx-nih-jama-psychiatry-glp1-cbt-alcohol-use-disorder-rct.md index 9b2323eea..226123d7f 100644 --- a/inbox/queue/2026-04-xx-nih-jama-psychiatry-glp1-cbt-alcohol-use-disorder-rct.md +++ b/inbox/archive/health/2026-04-xx-nih-jama-psychiatry-glp1-cbt-alcohol-use-disorder-rct.md @@ -7,10 +7,13 @@ date: 2026-04-01 domain: health secondary_domains: [] format: research-summary -status: unprocessed +status: processed +processed_by: vida +processed_date: 2026-05-02 priority: high tags: [GLP-1, semaglutide, alcohol-use-disorder, behavioral-health, mental-health, clinical-trial, RCT] intake_tier: research-task +extraction_model: "anthropic/claude-sonnet-4.5" --- ## Content