A recent study conducted by the Karolinska Institutet has found that people with type 2 diabetes who are treated with glucagon-like peptide-1 agonists, such as Ozempic, have a reduced risk of developing dementia. The findings, published in the journal eClinicalMedicine, suggest that this class of medication could have a protective effect on cognitive health for diabetic patients.
Type 2 diabetes is a chronic condition characterized by high blood sugar levels due to insulin resistance or inadequate insulin production. Individuals with this condition are at a significantly higher risk of developing dementia, a debilitating cognitive disorder.
With the increasing prevalence of type 2 diabetes globally, understanding how to mitigate its complications, including dementia, is growing in importance. Researchers aimed to explore whether newer diabetes medications like glucagon-like peptide-1 agonists and dipeptidyl peptidase-4 inhibitors could reduce the risk of dementia compared to older drugs such as sulfonylureas.
Glucagon-like peptide-1 agonists work by mimicking a hormone that increases insulin secretion, reduces glucagon secretion, and slows gastric emptying, thereby helping to regulate blood sugar levels. Dipeptidyl peptidase-4 inhibitors prevent the breakdown of incretin hormones, which also help to increase insulin production and decrease glucose levels.
The researchers utilized a comprehensive dataset from Swedish national registers, including the National Patient Register, the National Prescribed Drug Register, and several others. These registers provided detailed information on patient diagnoses, prescribed medications, and other relevant health data. The study included over three million Swedish residents aged 65 or older, spanning from January 1, 2004, to December 31, 2020. Participants had type 2 diabetes but no history of dementia or significant contraindications for the medications being studied.
The study design emulated a clinical trial by dividing participants into three groups based on the type of diabetes medication they initiated: glucagon-like peptide-1 agonists, dipeptidyl peptidase-4 inhibitors, or sulfonylureas. The primary outcome measured was the onset of dementia, identified through diagnosis codes or prescriptions for anti-dementia drugs. Participants were followed from the time they met the study’s eligibility criteria until they developed dementia, died, or reached the study’s end date.
Out of the 88,381 participants, those who started treatment with glucagon-like peptide-1 agonists had a notably lower incidence of dementia compared to those who used dipeptidyl peptidase-4 inhibitors or sulfonylureas. Specifically, the incidence rate of dementia was 6.7 per 1000 person-years for glucagon-like peptide-1 agonists, 11.8 for dipeptidyl peptidase-4 inhibitors, and 13.7 for sulfonylureas.
The weighted analysis, which adjusted for various baseline characteristics, showed that glucagon-like peptide-1 agonists were associated with a 31% lower risk of dementia compared to dipeptidyl peptidase-4 inhibitors and a 59% lower risk compared to sulfonylureas. Even when considering adherence to the medication (per-protocol analysis), the protective effect of glucagon-like peptide-1 agonists remained significant.
While the study’s findings are promising, there are several caveats to consider. First, despite extensive efforts to balance participant characteristics, residual confounding due to unmeasured factors may still be present. For instance, the severity of diabetes and cardiovascular risk could influence the outcomes. Although the study adjusted for many health conditions and socioeconomic factors, the precise duration and severity of diabetes were not fully accounted for.
Second, the diagnosis of dementia relied on national registers, which, while comprehensive, may not capture all cases accurately. Misclassification of dementia subtypes and underdiagnosis could impact the results.
Third, the study’s findings are based on observational data, which can suggest associations but cannot definitively establish causation. Randomized controlled trials are needed to confirm the protective effect of glucagon-like peptide-1 agonists against dementia.
Additionally, the study compared the relative effectiveness of three drug classes but did not measure their absolute effects against a placebo. Further research comparing these medications to placebos would provide a clearer picture of their true impact on dementia risk.
“This is important because it can help doctors make better decisions about which medicines to use for older patients with type 2 diabetes,” said Bowen Tang, a Ph.D. student in Sara Hägg’s research group at the Department of Medical Epidemiology and Biostatistics at Karolinska Institutet. “However, proper randomized trials are needed to establish with certainty that GLP-1 agonists reduce the risk of dementia.”
The study, “Comparative effectiveness of glucagon-like peptide-1 agonists, dipeptidyl peptidase-4 inhibitors, and sulfonylureas on the risk of dementia in older individuals with type 2 diabetes in Sweden: an emulated trial study,” was authored by Bowen Tang, Arvid Sjölander, Jonas W. Wastesson, Géric Maura, Pierre-Olivier Blotiere, Máté Szilcz, Jonathan K.L. Mak, Chenxi Qin, Michael Alvarsson, Dorota Religa, Kristina Johnell, and Sara Hägg.