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Two studies published in March by researchers at the Veterans Affairs Saint Louis Healthcare System highlight the clinical significance of glucagon-like peptide 1 receptor agonists (GLP-1s) and their impact on reducing substance use disorder (SUD) risks. The studies also explore the impact of GLP-1 discontinuation or interruption on their effectiveness in protection against the cardiovascular events.
In one study, Al-Aly et al assigned 606,434 veterans with type 2 diabetes to 1 of 2 protocols, comparing GLP-1s with sodium-glucose cotransporter-2 (SGLT-2) inhibitors, and followed the patients for up to 3 years. Al-Aly et al found that GLP-1s were “consistently associated” with a lower risk of developing SUDs, including those involving alcohol, cannabis, cocaine, nicotine, and opioids. The findings suggested “potential preventive effects across a broad range of addictive substances.”
In participants with pre-existing SUDs, GLP-1s were also associated with reduced risks of SUD-related emergency department visits, hospital admissions, and mortality, in addition to drug overdoses and suicidal behaviors. A study published in 2025 from the same research group reported that GLP-1s could have a variety of health benefits, including reducing the risk of incident alcohol and cannabis disorders, neurocognitive disorders (such as Alzheimer's disease and dementia), coagulation disorders, cardiometabolic disorders, infectious illnesses and several respiratory conditions, but less was known about the potential for preventing development of opioid use disorder and other SUDs.
GLP-1s target the brain’s reward pathways and have recently made attention-grabbing headlines regarding celebrity weight loss, with social media boosting public interest. One study, for example, found 100 videos on TikTok with the #Ozempic viewed nearly 70 million times.
Al-Aly et al used SGLT-2 inhibitors as active comparators because “they have no established direct actions on mesolimbic reward circuits in the brain, whereas GLP-1 receptors are present in areas of the brain involved in impulse control and reward signaling.”
The second study found that quitting or pausing GLP-1 treatment for 6 months could have a rebound effect and possibly reverse any progress. Discontinuing GLP-1 treatment is common, with rates ranging from 36% to 81% in the first year. Stopping or interrupting the treatment is often followed by weight regain and a rebound in inflammation, both major drivers in cardiovascular disease risk.
The study followed 132,551 VA patients using GLP-1s and 201,136 using sulfonylureas from 2017 through 2023. About two-thirds of participants took semaglutide, prescribed as Ozempic to treat diabetes and Wegovy to reduce obesity. A total of 26% of the participants stopped GLP-1 treatment during the follow-up period, with 64% occurring during the first year. Most (67%) treatment interruptions also came in the first year.
Compared with incident use of sulfonylureas, incident use of GLP-1s was associated with a reduced risk of heart attack, stroke, or death. Patients who took the GLP-1s without interruption > 3 years experienced an 18% lower risk for heart attack or stroke.
Cardiovascular benefits accumulated with continuous use over 3 years, but even brief periods of discontinuations or interruptions could progressively erode and ultimately reverse this protection, the researchers found. Discontinuing treatment for half a year was associated with an increased risk of major adverse cardiovascular events (incidence risk ratio [IRR], 1.04), while longer gaps were progressively associated with a higher risk of disease (IRR, 1.12 for 1 year; IRR, 1.16 for 2 years of interrupted use, respectively).
Dr. Ziyad Al-Aly, a study author and Chief of the Research and Education Service at the Veterans Affairs Saint Louis Healthcare System, called it “metabolic whiplash.” In an interview, he said it was important to caution patients that these medications “need to be taken for the long haul. This is not something (patients) can take for a month or 2 or 3 and get off of it. It's not going to work like that.”
Two studies published in March by researchers at the Veterans Affairs Saint Louis Healthcare System highlight the clinical significance of glucagon-like peptide 1 receptor agonists (GLP-1s) and their impact on reducing substance use disorder (SUD) risks. The studies also explore the impact of GLP-1 discontinuation or interruption on their effectiveness in protection against the cardiovascular events.
In one study, Al-Aly et al assigned 606,434 veterans with type 2 diabetes to 1 of 2 protocols, comparing GLP-1s with sodium-glucose cotransporter-2 (SGLT-2) inhibitors, and followed the patients for up to 3 years. Al-Aly et al found that GLP-1s were “consistently associated” with a lower risk of developing SUDs, including those involving alcohol, cannabis, cocaine, nicotine, and opioids. The findings suggested “potential preventive effects across a broad range of addictive substances.”
In participants with pre-existing SUDs, GLP-1s were also associated with reduced risks of SUD-related emergency department visits, hospital admissions, and mortality, in addition to drug overdoses and suicidal behaviors. A study published in 2025 from the same research group reported that GLP-1s could have a variety of health benefits, including reducing the risk of incident alcohol and cannabis disorders, neurocognitive disorders (such as Alzheimer's disease and dementia), coagulation disorders, cardiometabolic disorders, infectious illnesses and several respiratory conditions, but less was known about the potential for preventing development of opioid use disorder and other SUDs.
GLP-1s target the brain’s reward pathways and have recently made attention-grabbing headlines regarding celebrity weight loss, with social media boosting public interest. One study, for example, found 100 videos on TikTok with the #Ozempic viewed nearly 70 million times.
Al-Aly et al used SGLT-2 inhibitors as active comparators because “they have no established direct actions on mesolimbic reward circuits in the brain, whereas GLP-1 receptors are present in areas of the brain involved in impulse control and reward signaling.”
The second study found that quitting or pausing GLP-1 treatment for 6 months could have a rebound effect and possibly reverse any progress. Discontinuing GLP-1 treatment is common, with rates ranging from 36% to 81% in the first year. Stopping or interrupting the treatment is often followed by weight regain and a rebound in inflammation, both major drivers in cardiovascular disease risk.
The study followed 132,551 VA patients using GLP-1s and 201,136 using sulfonylureas from 2017 through 2023. About two-thirds of participants took semaglutide, prescribed as Ozempic to treat diabetes and Wegovy to reduce obesity. A total of 26% of the participants stopped GLP-1 treatment during the follow-up period, with 64% occurring during the first year. Most (67%) treatment interruptions also came in the first year.
Compared with incident use of sulfonylureas, incident use of GLP-1s was associated with a reduced risk of heart attack, stroke, or death. Patients who took the GLP-1s without interruption > 3 years experienced an 18% lower risk for heart attack or stroke.
Cardiovascular benefits accumulated with continuous use over 3 years, but even brief periods of discontinuations or interruptions could progressively erode and ultimately reverse this protection, the researchers found. Discontinuing treatment for half a year was associated with an increased risk of major adverse cardiovascular events (incidence risk ratio [IRR], 1.04), while longer gaps were progressively associated with a higher risk of disease (IRR, 1.12 for 1 year; IRR, 1.16 for 2 years of interrupted use, respectively).
Dr. Ziyad Al-Aly, a study author and Chief of the Research and Education Service at the Veterans Affairs Saint Louis Healthcare System, called it “metabolic whiplash.” In an interview, he said it was important to caution patients that these medications “need to be taken for the long haul. This is not something (patients) can take for a month or 2 or 3 and get off of it. It's not going to work like that.”
Two studies published in March by researchers at the Veterans Affairs Saint Louis Healthcare System highlight the clinical significance of glucagon-like peptide 1 receptor agonists (GLP-1s) and their impact on reducing substance use disorder (SUD) risks. The studies also explore the impact of GLP-1 discontinuation or interruption on their effectiveness in protection against the cardiovascular events.
In one study, Al-Aly et al assigned 606,434 veterans with type 2 diabetes to 1 of 2 protocols, comparing GLP-1s with sodium-glucose cotransporter-2 (SGLT-2) inhibitors, and followed the patients for up to 3 years. Al-Aly et al found that GLP-1s were “consistently associated” with a lower risk of developing SUDs, including those involving alcohol, cannabis, cocaine, nicotine, and opioids. The findings suggested “potential preventive effects across a broad range of addictive substances.”
In participants with pre-existing SUDs, GLP-1s were also associated with reduced risks of SUD-related emergency department visits, hospital admissions, and mortality, in addition to drug overdoses and suicidal behaviors. A study published in 2025 from the same research group reported that GLP-1s could have a variety of health benefits, including reducing the risk of incident alcohol and cannabis disorders, neurocognitive disorders (such as Alzheimer's disease and dementia), coagulation disorders, cardiometabolic disorders, infectious illnesses and several respiratory conditions, but less was known about the potential for preventing development of opioid use disorder and other SUDs.
GLP-1s target the brain’s reward pathways and have recently made attention-grabbing headlines regarding celebrity weight loss, with social media boosting public interest. One study, for example, found 100 videos on TikTok with the #Ozempic viewed nearly 70 million times.
Al-Aly et al used SGLT-2 inhibitors as active comparators because “they have no established direct actions on mesolimbic reward circuits in the brain, whereas GLP-1 receptors are present in areas of the brain involved in impulse control and reward signaling.”
The second study found that quitting or pausing GLP-1 treatment for 6 months could have a rebound effect and possibly reverse any progress. Discontinuing GLP-1 treatment is common, with rates ranging from 36% to 81% in the first year. Stopping or interrupting the treatment is often followed by weight regain and a rebound in inflammation, both major drivers in cardiovascular disease risk.
The study followed 132,551 VA patients using GLP-1s and 201,136 using sulfonylureas from 2017 through 2023. About two-thirds of participants took semaglutide, prescribed as Ozempic to treat diabetes and Wegovy to reduce obesity. A total of 26% of the participants stopped GLP-1 treatment during the follow-up period, with 64% occurring during the first year. Most (67%) treatment interruptions also came in the first year.
Compared with incident use of sulfonylureas, incident use of GLP-1s was associated with a reduced risk of heart attack, stroke, or death. Patients who took the GLP-1s without interruption > 3 years experienced an 18% lower risk for heart attack or stroke.
Cardiovascular benefits accumulated with continuous use over 3 years, but even brief periods of discontinuations or interruptions could progressively erode and ultimately reverse this protection, the researchers found. Discontinuing treatment for half a year was associated with an increased risk of major adverse cardiovascular events (incidence risk ratio [IRR], 1.04), while longer gaps were progressively associated with a higher risk of disease (IRR, 1.12 for 1 year; IRR, 1.16 for 2 years of interrupted use, respectively).
Dr. Ziyad Al-Aly, a study author and Chief of the Research and Education Service at the Veterans Affairs Saint Louis Healthcare System, called it “metabolic whiplash.” In an interview, he said it was important to caution patients that these medications “need to be taken for the long haul. This is not something (patients) can take for a month or 2 or 3 and get off of it. It's not going to work like that.”