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03-10-2024 | Dementia | News

SGLT2 inhibitors may lower risk for neurodegenerative disorders

Author: Matthew Williams

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medwireNews: Treating patients with type 2 diabetes with sodium-glucose cotransporter (SGLT)2 inhibitors may decrease the risk for developing incident dementia or Parkinson’s disease (PD), shows a retrospective study.

“Despite the favorable results of SGLT2 [inhibitors] on neurologic disorders in preclinical models, clinical benefits of SGLT2 [inhibitors] has primarily been focused on cardiorenal outcomes, but relatively little on neurologic outcomes,” observe Minyoung Lee (Yonsei University College of Medicine, Seoul, South Korea) and colleagues.

To address this, they analyzed data for 358,862 Korean patients (57.9% men) aged 40 years or older (mean age 57.8 years) with a primary or secondary diagnosis of type 2 diabetes, who received SGLT2 inhibitors or any other oral antidiabetic (OAD) treatment for at least 90 days from study entry between 2014 and 2019.

The 179,431 patients receiving SGLT2 inhibitors, either as monotherapy or in combination with other medications, were propensity-score matched to an equal number of those taking other types of OAD treatments. None of the participants had a history of neurodegenerative disease, cancer, or glucagon-like peptide-1 receptor agonist use.

During a mean follow-up of 2.88 years (2.06 years for SGLT2 inhibitor users and 3.70 years for nonusers), 6837 individuals developed dementia from any cause or PD, at an incidence rate of 66.1 per 10,000 person–years. For patients taking SGLT2 inhibitors, the rate was significantly lower than that for nonusers, at 48.2 versus 76.0 per 10,000 person–years.

Lee and colleagues report that, after adjusting for a raft of confounding variables including sociodemographic covariates, comorbidities, medication use, insulin use, anthropometric measures, health behaviors, and biochemical covariates, SGLT2 inhibitor use versus nonuse was associated with “significantly decreased risks” for AD by 19%, for vascular dementia by 31%, and for PD by 20%.

For secondary composite outcomes, the results showed that the use of SGLT2 inhibitors was associated with a significant 21% reduction in the risk for all-cause dementia and a significant 22% reduction in the risk for all-cause dementia or PD.

The researchers note that there was a decreasing incidence of neurodegenerative disease the longer patients were treated with SGLT2 inhibitors. This suggests “a potential causal relationship between the SGLT2 [inhibitor] use and the decreased risk of neurodegenerative diseases rather than the chance of reverse causality,” they say.

Further analyses confirmed the benefits of SGLT2 inhibitors in reducing the risk for dementia and PD were evident irrespective of sex, medications used, and the presence of comorbidities and diabetic complications, and were consistent across sensitivity analyses adjusting for blood pressure, glucose levels, lipid profiles, and kidney function.

Lee et al point out that age had a “marginal” effect on the association between SGLT2 inhibitor use and the risk for dementia and PD, with the risk reduced by 30% among participants younger than 65 years of age, compared with 22% among those aged 65 years and older. They say that this suggests that “using SGLT2 [inhibitors] before reaching a certain age might be more advantageous in reducing the risk of neurodegenerative diseases.”

The investigators acknowledge that, as dementia risk factors develop over a longer period than the relatively short study period of less than 5 years, it remains possible that “the use of SGLT2 [inhibitors] is more likely to delay the progression of dementia rather than prevent it completely.”

Therefore, “additional studies are required to validate the long- term stability of these observations,” they conclude.

medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2024 Springer Healthcare Ltd, part of the Springer Nature Group

Neurology 2024; doi:10.1212/WNL.0000000000209805

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