Thiazolidinediones (TZD) such as PioglitazoneAppears to Prevent Dementia, Whereas Sulfonylureas Appear to Increase Risk, New Observational Study of Patients type 2 diabetes Suggest.
Data from national electronic medical records from the US Department of Veterans Affairs showed a 22% lower risk of dementia with TZD monotherapy and a 12% higher risk with sulfonylurea monotherapy. metformin Monotherapy. The apparent protective effect of TZDs was greater in overweight or obese individuals. obesity.
“Our findings provide additional information to assist clinicians in choosing [glucose-lowering medications] mild or moderate type 2 diabetes and [who] increased risk of dementia,” Xin Tang and colleagues wrote in their paper. publish online October 11th BMJ Open Diabetes Research & Care.
According to Tang and colleagues, this result [glucose-lowering medications] On dementia, where previous findings are inconsistent. Studies with less than 3 years of his follow-up reported mostly non-associations, whereas studies with longer follow-up usually yielded protective results. The median follow-up he had was 6.8 years, long enough to detect treatment differences. ”
“supplement [a] metformin or [a] TZDs may partially counteract the prodemencia effect. “These findings may help guide drug selection for older patients with type 2 diabetes who are at high risk for dementia,” they observe.
Randomized trials needed to determine cause and effect
Dr Ivan Koychev, Senior Clinical Investigator at Oxford University Psychiatry, told the UK Science Media Center: Medications may help prevent dementia. ”
Koychev said the findings on TZDs, also known as glitazones, are glucagon-like peptide-1 (GLP-1) agonists and sodium-glucose cotransporter 2 (SGLT2) inhibitors.
“The main limitation of this study is that after the first 2 years, which the authors were interested in, the participants could have been prescribed any other type 2 diabetes medication (GLP-1 agonist or SGLT2 inhibitor). May reduce the risk of dementia and directly generate glitazones [TZD] Effects are more difficult to discern,” said Koychev.
And he noted that study design limits causal attribution. “It is also important to note that people with type 2 diabetes are at increased risk for both dementia and cognitive impairment, and these drugs are only prescribed to these patients. not from this patient group.”
Dr. James Connell, Head of Translational Sciences at Alzheimer’s Research UK, agrees. “This observational study found that people with type 2 diabetes taking thiazolidinediones had a lower risk of dementia than those taking the most common medications for type 2 diabetes, but it was It only shows an association between drug use and dementia risk, not a causal relationship.”
“Double-blind and placebo-controlled clinical trials are needed to see if the drug works. [TDZ] Whether you have diabetes or not, it may help lower your risk of dementia. If anyone has any questions about what treatment they are receiving, please consult your doctor,” he told the UK Science Media Centre.
Opposing effects of sulfonylureas, TZDs versus metformin
Tang et al., from the Department of Epidemiology and Biostatistics at the University of Arizona Mel and Enid Zuckerman College of Public Health Tucson, started hypoglycemic drugs between 2001 and 2017 and at least 1 year from 2001. They said he was over 60 years old and had no dementia at baseline.Mostly white (76.8%) and male (96.9%), two-thirds (63.1%) are obese, with an average of A1c It was 6.8%.
Overall, 31,125 developed all-cause dementia. The incidence was 8.2 cases per 1000 person-years for him, which ranged from 6.2 cases per 1000 person-years taking metformin monotherapy to 13.4 cases per 1000 person-years taking both sulfonylureas and TZDs. It was in the range of.
The hazard ratio (HR) for all-cause dementia for sulfonylurea monotherapy compared with metformin monotherapy was significantly 1.12.There was also an increased risk vascular dementiathe HR is 1.14.
In contrast, TZD monotherapy was associated with a significantly lower risk of all-cause dementia (HR, 0.78), Alzheimer’s disease (HR, 0.89) and vascular dementia (HR, 0.43), compared with metformin monotherapy.
The combination of metformin and TZDs also reduced the risk of all-cause dementia, whereas regimens containing sulfonylureas increased the risk of all-cause dementia and vascular dementia.
Most of the results did not change significantly when the drug exposure window was extended to 2 years.
More pronounced effect in obese people
The 1-year protective effects of TZD monotherapy and metformin plus TZD compared to metformin alone were more pronounced in participants aged 75 years or younger and with a body mass index (BMI) >25 kg/m.2 Comparison between people aged 75 and over and those with a normal BMI.
On the other hand, the risk of dementia from sulfonylureas was higher in people with higher BMI.
This work was funded in part by grants from the National Human Genome Institute, the National Science Foundation, the National Institute of Diabetes, Digestive and Kidney Diseases, and the National Heart, Lung, and Blood Institute. Zhou made no further disclosures. Koychev was the principal investigator of a study sponsored by the University of Oxford and Novo He was funded by Nordisk in which GLP-1 agonists semaglutide Reduces the risk of dementia in older people.
BMJ Open Diabreath Care. 2022;10:e002894. full text
Miriam E. Tucker is a freelance journalist based in Washington, DC. She is a regular contributor to her Medscape, and her other work appears in her The Washington Post, her Shots blog on NPR, and Diabetes Forecast magazine. She uses @MiriamETucker on her Twitter.
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