Semaglutide can protect against cognitive impairment and nicotine abuse

In a new study published in eClinicalMedicine, researchers found that the use of semaglutide, a drug prescribed primarily for type 2 diabetes, does not increase the risk of developing cognitive or psychiatric conditions. Surprisingly, semaglutide may even provide protection against cognitive impairment and nicotine abuse. These findings were derived by reviewing the electronic health records of tens of thousands of patients over the course of one year.

Semaglutide is an active ingredient in many medications, including Ozempic. It works by mimicking a hormone called glucagon-like peptide-1 (GLP-1), which helps regulate blood sugar levels. In addition to its effects on reducing glucose, semaglutide is also recognized for its potential benefits in weight control, which leads to its approval to treat obesity as well. The drug has received a lot of attention because of its effectiveness in improving metabolic health, reducing cardiovascular risks and helping to lose weight.

The focus of the new study stems from its growing use and emerging concerns about its safety profile. Although randomized controlled trials have confirmed the benefits of semaglutide in metabolic and cardiovascular health, there have been reports of negative neuropsychiatric effects, such as worsening mood and suicidal behavior.

These reports have prompted regulatory agencies such as the European Medicines Agency and the United Kingdom’s Medicines and Healthcare Regulatory Agency to review the safety of GLP-1 agonists, including semaglutide. The United States Food and Drug Administration also conducted a preliminary investigation but found no causal link. Despite this, concerns persisted within the medical community and society.

Because of these concerns, the researchers planned to provide a complete analysis of the risks associated with semaglutide by analyzing electronic health records from a large number of patients.

“I became interested in studying glucagon-like peptide-1 receptor agonists (GLP1-RAs) for neuropsychiatric diseases about 4 years ago, when, sadly, I saw a patient start drinking one of these drugs for diabetes, which also improved cognitive symptoms,” said study author Riccardo De Giorgi, a medical lecturer at the University of Oxford.

“I started planning a clinical trial, which is currently underway, to investigate this issue in healthy volunteers. Meanwhile, regulatory bodies such as the EMA and the MHRA have started research into GLP1-RAs after some reports of adverse neuropsychiatric events in people taking these drugs for diabetes or weight loss. bodies. So we thought we could use the information available on a platform called TriNetX to contribute to this research. “

TriNetX US Collaborative Network is a comprehensive database containing the anonymized electronic health records of more than 100 million patients in 62 health care organizations in the United States. The study focused on patients aged 18 and over who had been diagnosed with type 2 diabetes and received their first prescription for semaglutide between December 2017 and May 2021. The researchers compared these patients with three other groups, each given a different antidiabetic medication: sitagliptin, empagliflozin or glipizide.

The groups were carefully matched based on 179 variables, including demographics, socioeconomic status, lifestyle, health care utilization, comorbidities, and use of other medications. This intense game ensured that the comparison between the teams was as fair as possible.

The researchers tracked the presence of 22 neurological and psychiatric outcomes, including conditions such as cognitive impairment, dementia, epilepsy, depression, anxiety disorders and substance abuse. of drugs. They also reviewed all-cause mortality in the year following the initial order. The occurrence of these effects was analyzed using statistical methods that allowed a detailed comparison between semaglutide and other drugs.

The results revealed that semaglutide was not associated with an increased risk of any of the psychological or psychiatric conditions studied. In fact, semaglutide was associated with a lower risk of cognitive impairment and nicotine abuse compared to sitagliptin and glipizide.

Specifically, the risk of cognitive impairment was significantly lower in patients taking semaglutide compared to those taking sitagliptin (hazard ratio 0.72) and glipizide (hazard ratio 0.72). In addition, the risk of nicotine dependence was lower in the semaglutide group compared to all three comparator drugs.

These findings are consistent with another recent study, which found that people with type 2 diabetes treated with glucagon-like peptide-1 agonists, such as Ozempic, had less chance of developing dementia. The

“In addition to the lack of safety concerns, we were pleased to see that the use of semaglutide appeared to be positively associated with a lower risk of cognitive impairment and nicotine use,” De Giorgi said. tell PsyPost. “This is because there are several other studies that have looked at the mechanisms of action of these drugs, and they suggest that semaglutide may have a neuroprotective effect. while it works to control our brain’s reward system.”

“These methods, if wrong, may be explained by the problems mentioned above. Therefore, it has been interesting to see how the evidence from pre-clinical and clinical research is consistent.”

The study also found that semaglutide was associated with a lower risk of all-cause mortality compared to sitagliptin, glipizide and empagliflozin. This finding is very important, although it should be interpreted with caution due to possible limitations regarding the completeness of the death registration link in the database used.

“The main takeaway is that semaglutide appears to be safe from a neurological and psychological point of view in people taking it for the treatment of diabetes,” De Giorgi said. “Besides glucose control and weight loss, these drugs may have other benefits for the brain health of these patients, but we need clinical trials to confirm this.”

While these results are promising, it is important to note the study’s limitations. A major limitation is that the study is observational, meaning it can identify associations but cannot establish causation. Therefore, although the results suggest that semaglutide may have protective effects on mental health and nicotine abuse, it cannot be definitively stated that semaglutide causes these benefits.

“We must not make the mistake of including a cause between the exposure (semaglutide) and the results (mental and psychological problems) measured,” De Giorgi noted. “Therefore, we must be careful before considering any medical proposal. However, this study contributes to the growing body of research that provides encouragement regarding the negative neuropsychiatric effects of semaglutide and similar medications. ”

Future research should focus on confirming these findings with long-term controlled trials and exploring the mechanisms by which semaglutide may exert its protective effects on mental health and substance abuse. Clinical trials that include biomarkers of disease progression and long-term follow-up may be important to understand the potential neuroprotective and anti-inflammatory effects of semaglutide.

Despite these limitations, this study provides important information regarding the safety of semaglutide and its potential benefits beyond glycemic control in patients with type 2 diabetes. 2. These findings are particularly important considering the high burden of mental health problems in patients with diabetes and the growing use of GLP-1 RAs for various health conditions. .

“There is a lot of interest in investigating the potential of semaglutide and similar drugs now,” De Giorgi explained. “Other important studies in this context are for example: ISAP and EVOKE Plus for mental disorders, and STAR-T for alcohol use disorders. As mentioned above, my research group is also looking at methods of “Understanding the effects of semaglutide in healthy individuals – the OxSENSE study.”

He added: “This is an exciting part of medical research, but we must proceed with caution.” “Drugs like semaglutide may be powerful tools for many health conditions, but they are new drugs and we need more research. In addition, these drugs do not have the potential to be monotherapy, so significant research investment may be needed to determine exactly which people are most likely to benefit, and which people are likely to have problems unwelcome.”

The study, “12-month neurological and cognitive outcomes of semaglutide use for type 2 diabetes: propensity-score matched cohort study,” was written by Riccardo De Giorgi, Ivan Koychev, Amanda I. Adler, Philip J. Cowen, Catherine J . Harmer, Paul J. Harrison, and Maxime Taquet.