Evaluating the Benefits and Risks of Weight Loss Drugs

By Irene Yeh 

April 3, 2025 | Weight loss medications are in “skyrocketing” utilization, according to Ziyad Al-Aly, clinical epidemiologist at the Washington University School of Medicine in St. Louis (WashU Medicine). Yet there have been no comprehensive investigations or studies on the effectiveness and risks of glucagon-like peptide-1 receptor agents (GLP-1RA). Researchers at the WashU Medicine collaborated with the Veterans Affairs (VA) St. Louis Health Care System to examine and evaluate more than two million people with diabetes taking popular weight loss drugs such as Ozempic.  

The Benefits and Risks 

Dubbed ‘miracle drugs,’ GLP-1RA’s have gained a reputation of enhancing weight loss among users. While this is helpful for patients with obesity and/or obesity-related illnesses, information on the drugs’ effects on the organ systems are sparse. The team used the VA’s database to examine a cohort of almost 216,000 veterans who were treated for diabetes from October 2017 to December 2023. The veterans who were on GLP-1RA's were compared to more than 2.4 million individuals who were not on GLP-1RA’s, including sulfonylureas, dipeptidyl peptidase 4 (DPP4), sodium-glucose cotransporter-2 (SGLT2), and non-GL-1RA antihyperglycemics. The team developed an atlas of the associations of GLP-1RA use versus each comparator with 175 health outcomes, “leaving no stone unturned” (Nature Medicine, DOI: https://doi.org/10.1038/s41591-025-03542-9).  

“The VA operates the largest integrated health care system in the US and all of its data is digitized, making it an ideal environment to study this question,” explains Al-Aly. The results revealed that GLP-1RA medications reduced the risks of substance use disorders, psychotic disorders (e.g. suicidal ideation and schizophrenia), seizures, neurocognitive disorders (e.g. Alzheimer’s disease and dementia), clotting disorders, infections, chronic obstructive pulmonary disease, liver failure and cancer, and inflammatory bowel disease. These discoveries are greatly beneficial, as they provide hopeful treatment options for patients with any of the above-mentioned illnesses and disorders. 

However, the risks found included several gastrointestinal disorders (including nausea, vomiting, diarrhea, constipation, gastroesophageal reflux disease, stomach paralysis, diverticulosis, and diverticulitis), low blood pressure, fainting, sleep problems, headaches, kidney stones and inflammation, and drug-induced pancreatis. It was a novel finding that GLP-1RA drugs can negatively affect the kidneys and pancreas. 

While GLP-1RA’s showed positive effects, the magnitude of associated benefits is modest, with only 10-20% reduction for most outcomes. “These drugs work; I understand the enthusiasm,” says Al-Aly. “But we really don’t know the long-term effects of using them and also the effects of discontinuation.” 

The findings of this evaluation provide insight on potential treatment for patients with certain diseases, but they also serve to emphasize and remind patients and clinicians that these ‘miracle drugs’ still carry great risks. Those who are on GLP-1RA drugs must be monitored closely and carefully.