Massive study looks at benefits, risks of GLP-1 weight-loss drugs
NEW YORK, Jan. 22 (UPI) -- As demand for weight-loss injections sold under brand names such as Ozempic and Wegovy continues to soar, a new study has uncovered neurological and behavioral health benefits amid increased risks for pancreatitis and kidney disease.
The study was published this week in the journal Nature Medicine.
With the drugs' novelty and soaring popularity, it's important for consumers to know about the effects on all organ systems and become aware of the need for careful monitoring, researchers noted.
The downside was finding that the drugs produced an increased risk of gastrointestinal disorders, low blood pressure, fainting, arthritic disorders, kidney stones, inflammation between the kidney tubules and drug-induced pancreatitis, the study noted.
While these negative effects are not common, they can be very serious. Kidney problems may occur without symptoms until an advanced stage with limited treatment options, researchers said.
Despite these potential side effects, Americans continue to use these drugs in huge numbers.
"We saw skyrocketing utilization" of these drugs, the study's senior and corresponding author, Dr. Ziyad Al-Aly, told UPI in explaining why he and his colleagues undertook this study.
Yet, "we realized that no one had comprehensively investigated the effectiveness and risks [of these drugs] across all possible health outcomes," said Al-Aly, a clinical epidemiologist at Washington University School of Medicine in St. Louis.
"So, we decided to conduct this comprehensive study to examine all 175 possible health outcomes, leaving no stone unturned," said Al-Aly, who also serves as director of the Clinical Epidemiology Center at VA St. Louis Health Care System, where he is head of the research and development service.
These drugs "represent a transformative advancement in medicine, and our goal was to thoroughly map this new landscape," he said.
The medications are known as glucagon-like peptide-1 receptor agonists (GLP-1RA) and include Mounjaro and Zepbound, which are injectables.
They lower blood sugar and energy intake by activating the GLP-1 receptor in the pancreas, brain and other parts of the body. Some patients and even doctors have called them "miracle drugs" because of pronounced weight loss among users.
To identify people with diabetes who used GLP-1RAs, the researchers extracted information on those with diabetes from the U.S. Department of Veterans Affairs healthcare databases.
They found 215,970 GLP-1RA users, 536,068 consumers on three commonly used blood sugar-lowering medications and 1,203,097 usual-care individuals. The total of 1,955,135 patients were enrolled between October 2017 and December 2023 and underwent follow-up for 3.7 years.
About 1 in 8, or 12%, reported ever taking the "increasingly popular class of prescription drugs [GLP-1] used for weight loss and to treat diabetes or prevent heart attacks or strokes for adults with heart disease," according to the KFF Health Tracking Poll May 2024.
This figure included 6% who said they were on such a drug at the time.
Al-Aly and his colleagues found that these sought-after medications "have broad health benefits that extend well beyond weight loss," he said. "They display effectiveness in addiction disorders, clotting disorders, seizures, infections, Alzheimer's disease and dementia."
Reduced risk for Alzheimer's and dementia may stem from the drugs' capability to lessen inflammation in the brain and prompt weight loss.
Even a modest effect -- about a 10% to 20% decline for most health outcomes -- is noteworthy for conditions with few effective treatment options -- for instance, dementia. So, the drugs may be most helpful in conjunction with lifestyle changes or other medications, Al-Aly said.
People taking these medications also experienced decreased risks of seizures and addiction to substances such as alcohol, cannabis, stimulants and opioids.
The drugs act on receptors expressed in brain areas involved in impulse control, reward and addiction, which could be the reason behind their effectiveness in suppressing appetite and addiction disorders, researchers said.
The drugs also resulted in lower risks of suicidal ideation, self-harm, bulimia and psychotic disorders, such as schizophrenia, they said, while cautioning that the drugs pose some serious risks that merit attention.
Al-Aly and his team also confirmed previous research findings describing the drugs' potential to minimize risks for heart attack, stroke and other cardiovascular concerns.
Other experts credited the researchers for embarking on a large-scale study that investigated possible unanticipated health outcomes of these popular weight-loss drugs.
"This is an extremely important and powerful study that examines 175 health outcomes in almost 2 million diabetic patients followed for 3.7 years," said Dr. Elena Ambrogini, director of the Division of Endocrinology and Metabolism at the University of Arkansas for Medical Sciences in Little Rock. She was not involved in the study.
The use of these weight-loss drugs "has greatly expanded in the last few years," as they have become the "standard of care in diabetes and obesity," said Ambrogini, who also is a staff endocrinologist and research scientist at Central Arkansas Veterans Healthcare System.
As a result, she said, expanding knowledge about the effectiveness and risks of these medications on other organs will help patients and doctors make informed decisions about care and may influence the direction of future research.
Although the study examined older, mostly White male U.S. veterans, the overall number of patients is large. It also included female participants across a large age span and different races, rendering the findings more applicable to the general population, Ambrogini added.
"These medications have unprecedented efficacy for treating obesity in diabetes and obesity in general," said Dr. W. Timothy Garvey, an endocrinologist and senior scientist at the University of Alabama-Birmingham Nutrition Obesity Research Center.
The study follows patients at a time when many were on less effective first-generation or lower-dose medications, so the benefits and risks of newer drugs remain unclear from this data, Garvey said.
Nonetheless, the findings confirm these drugs' effectiveness in reducing risk of cardiovascular outcomes in patients with diabetes, said Dr. Simin Liu, chair and distinguished professor in the Department of Epidemiology & Biostatistics at the University of California-Irvine Joe C. Wen School of Population & Public Health.
"It's crucial to continue supporting research in diabetes management as ongoing studies will help refine and optimize treatment options, ultimately benefiting patients worldwide," Liu said.
Patients still should consult their clinicians about whether these drugs are appropriate for them, considering their particular health profiles, he said.
The drugs' actions include releasing glucose-stimulated insulin, slowing of gastric emptying, which increases a feeling of fullness, and arousing neurons in the brain's satiety center. This appears to influence appetite for food, alcohol, tobacco or drugs, said Dr. Holly Kramer, a professor of public health sciences and medicine in the Division of Nephrology and Hypertension at Loyola University Chicago.
However, not every patient can tolerate the drugs. Some people become very nauseous and are unable to eat at all. Then they develop depletion of water and sodium, which can lead to kidney injury, low blood pressure and falls. In individuals with advanced chronic kidney disease, clinicians may prescribe lower dosages at the outset and then slowly escalate the amount, Kramer said.
Eventually, other uses could emerge for these medications besides weight loss, she said, adding that they "may be one of the most important medication breakthroughs in the 21st century."
