Canada: Study on SGLT2 Inhibitors and Dementia Risk

The new use of sodium-glucose cotransporter-2 (SGLT2) inhibitors compared with dipeptidyl peptidase 4 (DPP-4) inhibitors confers 20% lower dementia risk in older people with type 2 diabetes, a recent study published in Diabetes Care has stated.

SGLT2 inhibitors are a class of prescription medications approved by the FDA to be used with exercise and diet to lower blood sugar in adults with type 2 diabetes. The drugs in this class include:

• Empagliflozin
• Dapagliflozin
• Canagliflozin

DPP-4 inhibitors, also called gliptins, are a class of oral diabetic medications which are FDA-approved for treating type 2 diabetes in adults. FDA-approved DPP inhibitors include:

• Linagliptin
• Saxagliptin
• Alogliptin
• Sitagliptin

It is known that type 2 diabetes raises the risk of dementia, but there is a lack of clear evidence to recommend interventions that can lower this risk. For this purpose, Walter Swardfager from the University of Toronto in Toronto, Ontario, Canada, and colleagues aimed to determine whether the new use of SGLT2 inhibitors compared with DPP-4 inhibitors was linked with a lower risk of dementia in a population-based retrospective cohort study.

The cohort included Ontario residents aged ≥66 who were new users of a DPP-4 inhibitor or an SGLT2 inhibitor from 1 July 2016 - 31 March 2021. A validated algorithm for Alzheimer's disease and related dementias was used to identify incident dementia. Adjusted hazard ratios (aHR) for time to incident dementia were obtained using Propensity-score weighted Cox proportional hazards models.

The observation window was initiated at 1-year lag time from cohort entry to address disease latency and reverse causality. The primary analysis followed the intention-to-treat exposure definition, and secondary as-treated research was conducted.

Study Findings

• Among 106,903 individuals, SGLT2 inhibitors compared with DPP-4 inhibitors were associated with a lower risk of dementia (14.2/1,000 person-years; aHR 0.80) over a mean follow-up of 2.80 years from cohort entry.
• When stratified by different SGLT2 inhibitors, dapagliflozin exhibited the lowest risk (aHR 0.67), followed by empagliflozin (aHR 0.78), whereas canagliflozin showed no association (aHR 0.96).
• The as-treated analysis observed a more significant association (aHR 0.66) than the intention-to-treat analysis.

"The results indicate an association between SGLT2 inhibitors and lower dementia risk in older people with type 2 diabetes," the authors conclude. "Randomized controlled trials are warranted."

Reference

Che-Yuan Wu, Carina Iskander, Christa Wang, Lisa Y. Xiong, Baiju R. Shah, Jodi D. Edwards, Moira K. Kapral, Nathan Herrmann, Krista L. Lanctôt, Mario Masellis, Richard H. Swartz, Hugo Cogo-Moreira, Bradley J. MacIntosh, Jennifer S. Rabin, Sandra E. Black, Refik Saskin, Walter Swardfager; Association of Sodium–Glucose Cotransporter-2 Inhibitors with Time to Dementia: A Population-Based Cohort Study. Diabetes Care 2022; dc221705. https://doi.org/10.2337/dc22-1705