GLP-1 agonists reduce substance use disorder (SUD): a role for chemsex drugs?
6 March 2026. Related: Early access, Side effects, Coinfections and complications.
Simon Collins, HIV i-Base
When i-Base reported several GLP-1 studies in people living with HIV from CROI 2024, we included a discussion about whether anecdotal reports of breaking the reward mechanism associated with reduced craving for food might have a role to reduce dependence on chemsex drugs which currently have no effective treatment to support and manage withdrawal. [1]
This impact on breaking the craving for food has also been reported as a potential mechanism for the weight loss seen with GLP-1 receptor agonist – and anecdotal reductions in drinking less alcohol and smoking fewer cigarettes, also supported results from a small phase 2 study. [2]
A large observational study in BMJ adds further data to this potential benefit from use in substance used disorder (SUD). [3]
This study involved more than 600,000 veterans with diabetes (mean age 65 years, 90% male) who received their care in the large Veteran’s Affairs cohort and who were treated with GLP-1 receptor agonists in two protocols. This depending on whether SGLT-2 inhibitors were a comparative treatment in people without SUD (Protocol 1 – with seven trials on each substance) or as an additional treatment in people with existing SUD (Protocol 2 – a single study with clinical endpoints).
The results showed a clear and consistent reduction in the use of cannabis, cocaine, nicotine, opioid and other substances, together with reduced hospital visits, mortality and suicide. See Table 1.
The use of GLP-1 receptor agonists compared to SGLT-2 inhibitors was associated with significantly reduced risk of disorders related to each substance in Protocol 1 and significantly fewer clinical events in Protocol 2.
Table 1: Different risk of incident substance use disorders and clinical events
| Substance / event | HR | 95%CI | NRD per 1000 people (95%CI) |
| Protocol 1: Incident SUDs by substance | |||
| Alcohol use | 0.82 | 0.78 to 0.85 | −5.57 (−6.61 to −4.53) |
| Cannabis use | 0.86 | 0.81 to 0.90 | −2.25 (−3.00 to −1.50) |
| Cocaine use | 0.80 | 0.72 to 0.88 | −0.97 (−1.37 to −0.57) |
| Nicotine use | 0.80 | 0.74 to 0.87 | −1.64 (−2.19 to −1.09) |
| Opioid use | 0.75 | 0.67 to 0.85 | −0.86 (−1.19 to −0.52) |
| Other SUDs | 0.87 | 0.81 to 0.94 | −1.12 (−1.68 to −0.55) |
| Composite of all incident SUDs | 0.86 | 0.83 to 0.88 | −6.61 (−7.95 to −5.26) |
| Protocol 2 (SUD-related clinical events) | |||
| ER visits | 0.69 | 0.61 to 0.78 | −8.92 (−11.59 to −6.25) |
| Hospital admissions | 0.74 | 0.65 to 0.85 | −6.23 (−8.73 to −3.74) |
| Mortality | 0.50 | 0.32 to 0.79 | −1.52 (−2.32 to −0.72) |
| Drug overdose | 0.61 | 0.42 to 0.88 | −1.49 (−2.43 to −0.55) |
| Suicidal ideation or attempt | 0.75 | 0.67 to 0.83 | −9.95 (−13.14 to −6.77) |
Key: HR = Hazard ratio, CI = Confidence Interval, NRD = net 3-year risk difference per 1000 people
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These data support pilot studies to see whether GLP-1 agonist could have a similar protective role in other substance use disorders that affect people living with HIV and other marginalised communities.
This include to break the use and need for chemsex drugs that include methamphetamine (crystal/crystal meth/Tina/meth), mephedrone (meph) and GHB/GBL (G, Gina).
Although the manufacturers of these drugs have not supported research studies that include people living with HIV, new research might become possible to plan now in countries where patents on semaglutide expire in 2027.
References
- CROI 2024: HIV studies with semaglutide: significant benefits but limited access for treatment and research. HTB (10 March 2024).
https://i-base.info/htb/47286 - Semaglutide reduces alcohol and cigarette use in a randomised phase 2 study. HTB (12 February 2025).
https://i-base.info/htb/50245 - Cai M et al. Glucagon-like peptide-1 receptor agonists and risk of substance use disorders among US veterans with type 2 diabetes: cohort study. BMJ 2026392:e086886, doi: 10.1136/bmj-2025-086886 (04 March 2026).
https://www.bmj.com/content/392/bmj-2025-086886