Diabetes Drugs GLP-1RA and SGLT2I Lower Dementia Risk in Older Adults, Study Finds

Diabetes Drugs GLP-1RA and SGLT2I Lower Dementia Risk in Older Adults, Study Finds

A new study links two widely prescribed diabetes drugs to a 33–43% lower risk of Alzheimer's and related dementias, offering hope for transforming existing treatments to address one of the most devastating diseases of aging.

A study recently published in the journalJAMA -Neurologydetermines the potential impact of new anti-diabetes drugs on the risk of Alzheimer's disease and related dementia (ADRD).

Novel approaches to treating ADRD

ADRD, characterized by progressive cognitive impairment, currently affects approximately seven million older adults in the United States. Researchers predict that up to 14 million people in the United States will be diagnosed by 2060. Recently, the US Food and Drug Administration (FDA) has approved several disease-modifying treatments for ADACANMABS treatments and donanemab, some of which are aducanumab, lecanemab, and donanemab, and donanemab, and donanemab, and donanemab, and donanemab, and donanemab, and donanemab, and donanemab, and donanemaNemab) and donanemab; However, their effectiveness and risks remain unclear.

To overcome the high costs and potential adverse effects associated with novel AD drugs, researchers are increasingly interested in repurposing existing drugs for novel therapeutic indications. For example, several studies have recently reported that low-glucose medications such as glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium glucose cotransporter-2 inhibitors (SGLT2Is) may reduce the risk of ADRD. Despite these observations, the association between these medications and ADRD risk remains unclear.

Study results

Electronic health data from a Florida+ Clinical Research Consortium were obtained between January 2014 and June 2023. All patients were at least 50 years old and diagnosed with T2DM without prior diagnosis of ADRD.

Patients prescribed either GLP-1RAS or SGLT2Is were more likely to be female, younger than the overall age of the T2DM cohort, and have higher blood pressure compared to patients prescribed other glucose-lowering medications.

The incidence of ADRD in patients prescribed GLP-1RS compared to other anti-diabetes drugs was 4.35 and 6.6 per 1,000 people, respectively. Patients prescribed SGLT2Is also had a lower risk of ADRD, at a rate of 4.19 cases per 1,000 people compared to 7.23 cases in patients prescribed other glucose-lowering medications.

These results indicate that both GLP-1RA use and SGLT2 use were associated with a significantly reduced risk of developing ADRD. No significant difference in ADRD risk was observed when comparing the use of GLP-1RA and SGLT2.

GLP-1RAs are associated with numerous health benefits that may contribute to the reduced risk of ADRD in diabetics, some of which include reduced neuroinflammation, improved insulin sensitivity in the brain, and greater neurogenesis. These drugs can also promote synaptic plasticity while reducing the accumulation of amyloid-β and tau proteins.

SGLT2Is may also increase blood flow to the brain and reduce exposure to oxidizing molecules while promoting mitochondrial function.

Both drug classes are associated with improved vascular health and beneficial metabolic effects that are strongly linked to cognitive performance. The mechanisms of action shared between both GLP-1RAS and SGLT2IS likely contribute to their similar risk reduction profile for ADRD.

Use of GLP-1RA was associated with a 33% lower risk of ADRD, while use of SGLT2I was associated with a 43% lower risk compared to other glucose-lowering medications. “

Future prospects

The development of ADRD is a protracted process that typically occurs over several years, with pathologic changes often occurring before clinical symptoms can be detected. Therefore, due to the short follow-up period for the current analysis, additional studies are required to confirm the long-term neuroprotective effects of GLP-1RAS and SGLT2Is.

Longitudinal studies, particularly randomized controlled trials (RCTs), are needed to monitor the long-term effects of GLP-1RA and SGLT2I on ADRD risk in diabetic patients. Additional studies that employ more rigorous analytical methods while adjusting for covariate factors are also warranted.

However, the study results suggest that GLP-1RAS and SGLT2Is have neuroprotective effects that could be used as part of broader therapeutic regimens to prevent ADRD in diabetic patients. Notably, the reduced ADRD risk remained consistent when different ethnicities, gender, obesity status, and insulin or metformin use were considered in the analysis, indicating the generalizability of these observations.

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