Study: GLP-1s ‘hold promise’ for treating a wide range of diseases and health outcomes

Key takeaways:

• GLP-1 receptor agonists reduced the risk for dozens of possible adverse health outcomes.
• However, many health outcomes, like nausea and vomiting, saw their risks increase with GLP-1 use.

Glucagon-like peptide-1 receptor agonist use corresponded with risk reductions for dozens of diseases and adverse health outcomes, such as dementia and stroke, a new analysis published in Nature Medicine showed.

The data show that the drugs “have a wide array of beneficial effects but not without risks,” Ziyad Al-Aly, MD, FASN, an assistant professor of medicine at the Washington University School of Medicine in St. Louis, said during a press briefing.

Al-Aly explained that the use of GLP-1s has soared in the last couple years while multiple studies have captured their far-reaching benefits, but “[we] realized that no one has comprehensively investigated the effectiveness and risks of GLP-1 receptor agonists across all possible health outcomes.”

In the study, Al-Aly and colleagues mapped out associations between GLP-1s and 175 possible health outcomes by comparing a cohort of people with diabetes who used the treatments (n = 215,970) with:

• those who used sulfonylureas (n = 159,465);
• those who used dipeptidyl peptidase-4, or DPP-IV, inhibitors (n = 117,989);
• those who used sodium-glucose cotransporter-2, or SGLT2, inhibitors (n = 258,614);
• a control group made up of an equal proportion of people using sulfonylureas, DPP-IV inhibitors and SGLT2 inhibitors (n = 536,068); and
• a control group of people who continued use of non-GLP-1 receptor agonist antihyperglycemics, defined as usual care (n = 1,203,097).

The researchers built study cohorts with information taken from the U.S. Department of Veterans Affairs databases, at a median follow-up of 3.6 years.

The researchers found that the use of GLP-1s corresponded with a decreased risk for 42 health outcomes vs. usual care.

They observed risk reductions for multiple substance use disorders, such as cannabis use disorder (HR = 0.88; 95% CI, 0.83-0.93), alcohol use disorder (HR = 0.89; 95% CI, 0.86-0.92) and opioid use disorder (HR = 0.87; 95% CI, 0.82-0.92).

The analysis also showed that GLP-1 receptor agonist use may be beneficial for other mental health outcomes because the risks for suicidal ideation, attempt or intentional self-harm (HR = 0.9; 95% CI, 0.86-0.94), schizophrenia and other psychotic disorders (HR = 0.82; 95% CI, 0.76-0.89) and neurocognitive disorders like Alzheimer’s disease (HR = 0.88; 95% CI, 0.78-0.99) and dementia (HR = 0.92; 95% CI, 0.88-0.97) all decreased.

The medications further resulted in risk reductions for some infectious diseases, including bacterial infections (HR = 0.88; 95% CI, 0.86-0.9) and pneumonia (HR = 0.84; 95% CI, 0.82-0.86).

Al-Aly and colleagues noted association for GLP-1 use and reduced risk for several cardiovascular events like heart failure (HR = 0.89; 95% CI, 0.87-0.91), cardiac arrest (HR = 0.78; 95% CI, 0.71-0.85), pulmonary hypertension (HR = 0.82; 95% CI, 0.78-0.85), ischemic stroke (HR = 0.93; 95% CI, 0.9-0.96) and myocardial infarction (HR = 0.91; 95% CI, 0.87-0.94), as were the risks for chronic kidney disease (HR = 0.97; 95% CI, 0.96-0.99) acute kidney injury (HR = 0.88; 95% CI, 0.86-0.9) and COPD (HR = 0.9; 95% CI, 0.87-0.92).

“We also saw reduced risk for coagulation disorders including deep vein thrombosis and embolism,” Al-Aly said at the briefing.

GLP-1s also demonstrated potential downsides, increasing the risk for 19 health outcomes. These included abdominal pain (HR = 1.12; 95% CI, 1.1-1.13), gastritis (HR = 1.1; 95% CI, 1.06-1.14), nausea and vomiting (HR = 1.3; 95% CI, 1.26-1.33), sleep disturbances (HR = 1.12; 95% CI, 1.1-1.14), headaches (HR = 1.1; 95% CI, 1.08-1.13) and arthritis (HR = 1.11; 95% CI, 1.09-1.13).

“We also saw an increased risk of low [BP],” Al-Aly added. “Some people actually have low [BP] to the point where they have syncope.”

There were some study limitations. For example, individuals in the cohorts were older and mostly white men, thus hurting the results’ generalizability to the general population, while the researchers could not rule out residual confounding.

Aly-Aly concluded that treating obesity and metabolic syndrome with GLP-1s is “likely to have broad benefits that extend beyond just reducing BMI or reducing weight,” while the drugs “hold promise” for addressing other diseases.