Weight-loss drugs linked to unexpected benefits and risks

Demand for weight-loss medications such as Ozempic and Wegovy continues to rise, with a recent study reporting that one in eight Americans has taken or is currently taking the drugs to cope with diabetes, heart disease or obesity. 

Formally known as glucagon-like peptide-1 receptor agonists (GLP-1RA) and including brands like Mounjaro and Zepbound, these weight-loss drugs have been dubbed “miracle drugs” due to the notable weight loss they often induce.

Their benefits for human health are well recognized, yet little has been known about how they affect different organ systems.

Analyzing the benefits and risks of weight-loss drugs 

Scientists at Washington University School of Medicine in St. Louis and the Veterans Affairs (VA) St. Louis Health Care System set out to address this knowledge gap.

The team conducted a systematic evaluation of health outcomes among more than two million individuals with diabetes who have used these medications. 

The analysis revealed strong benefits to cognitive and behavioral health, while also showing increased risks for pancreatitis and kidney conditions, among others. 

The study, published in Nature Medicine, sheds new light on the overall profile of GLP-1RA drugs.

A systematic look across all organ systems

Study senior author Dr. Ziyad Al-Aly is a clinical epidemiologist and nephrologist at the John J. Cochran Veterans Hospital in St. Louis.

“Given the drugs’ newness and skyrocketing popularity, it is important to systematically examine their effects on all body systems – leaving no stone unturned – to understand what they do and what they don’t do,” said Dr. Al-Aly.

“Our approach has allowed us to build a comprehensive atlas mapping the associations of GLP-1RA spanning all organ systems. The study’s results provide insights into some known and previously unrecognized benefits and risks of GLP-1RA that may be useful to inform clinical care and guide research agendas.”

GLP-1RA medications are taken weekly by injection and work by simulating hormones that decrease appetite and slow digestion, promoting prolonged satiety. Alongside a balanced diet and regular exercise, they have become an increasingly popular method of addressing diabetes, obesity, and certain heart conditions.

Weight-loss drugs and mental health

To gain a clearer picture of how these drugs influence human health, researchers at Washington University analyzed de-identified records from the U.S. Department of Veterans Affairs. 

The team compared 175 health outcomes in veterans who used GLP-1RA medications to those who used other diabetes treatments, such as Jardiance, Glipizide, and Januvia. The dataset encompassed over two million veterans of varying ages, races, and sexes treated for diabetes between October 2017 and December 2023.

The study revealed that GLP-1RA medications significantly benefit neurological and behavioral health, including decreased risks of seizures and addiction to various substances such as alcohol, cannabis, stimulants and opioids. 

The findings also indicated a reduction in suicidal ideation, self-harm, bulimia and psychotic disorders such as schizophrenia, and a decreased risk of neurological diseases such as Alzheimer’s and dementia.

Possible mechanisms behind the benefits

“Interestingly, GLP-1RA drugs act on receptors that are expressed in brain areas involved in impulse control, reward and addiction – potentially explaining their effectiveness in curbing appetite and addiction disorders,” said Dr. Al-Aly. 

“These drugs also reduce inflammation in the brain and result in weight loss; both these factors may improve brain health and explain the reduced risk of conditions like Alzheimer’s disease and dementia.”

Even though the associated health benefits generally provide only a 10 percent to 20 percent reduction in certain risks, they hold particular promise for diseases with few effective treatments. 

“However, the modest effect does not negate the potential value of these drugs, especially for conditions where few effective treatment options exist, for example, dementia,” noted Dr. Al-Aly. “This may also imply that these drugs are most beneficial when used in conjunction with other interventions, such as lifestyle changes or other medications.”

The study reaffirmed existing evidence that GLP-1RA medications lower risk for heart attacks, strokes, and other heart-related concerns.

Recognizing the risks of weight-loss drugs 

Though these findings highlight the broad advantages of GLP-1RA drugs, the study also confirmed certain risks, especially in the gastrointestinal tract. 

“These have been well documented in the research and anecdotally,” said Dr. Al-Aly. “Our study confirmed such findings.” Patients may experience nausea, vomiting, diarrhea, or, in rare instances, stomach paralysis.

Additionally, the study revealed newer information on how these drugs can potentially harm the pancreas and kidneys. While not common, pancreatitis can occur and poses a serious threat, and kidney problems may progress unnoticed until they reach an advanced stage. 

“GLP-1RA drugs can have broad health benefits,” said Dr. Al-Aly. “However, they are not without risks. Our findings underscore the possibility for wider applications for these medications but also highlight important risks that should be carefully monitored in people taking these drugs.”

Implications for future use

As more people turn to GLP-1RA medications like Ozempic, Wegovy, Mounjaro, and Zepbound, understanding both their benefits and their potential downsides is key. 

The large-scale veteran population data examined in this study presents a detailed view of how these drugs interact with multiple body systems. 

Ultimately, this awareness can help physicians and patients make more informed decisions about managing diabetes, obesity, and heart disease, while emphasizing the need for vigilance in monitoring for adverse effects, particularly in the pancreas and kidneys.

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