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TOPLINE:

In adults with type 2 diabetes (T2D), the use of SGLT2 inhibitors was associated with lower risks for delirium and all-cause mortality than the use of metformin, with more prominent protective effects in high-risk patients such as those aged 80 years or older.

METHODOLOGY:

• T2D is a recognized risk factor for delirium. Although several studies have shown neuroprotective effects of metformin and cognitive protection by SGLT2 inhibitors, a real-world comparative analysis is lacking.
• Researchers conducted a retrospective cohort study using data from electronic health records of healthcare organizations worldwide for a head-to-head comparison of metformin and SGLT2 inhibitors in preventing delirium among patients with T2D.
• After propensity score matching, they included adults with T2D who initiated either SGLT2 inhibitors (n = 79,723; mean age, 65.52 years; 39.77% women) or metformin (n = 79,723; mean age, 65.62 years; 39.43% women) between January 2005 and January 2025.
• The primary outcome was the first recorded diagnosis of delirium, and the secondary outcome was all-cause mortality.

TAKEAWAY:

• The use of SGLT2 inhibitors was associated with a lower risk for incident delirium than the use of metformin (adjusted hazard ratio [aHR], 0.91; 95% CI, 0.87-0.95).
• The risk for all-cause mortality was also reduced in patients who used SGLT2 inhibitors (aHR, 0.85; 95% CI, 0.87-0.88).
• The protective effect of SGLT2 inhibitors against delirium was most prominent in patients aged 80 years or older (aHR, 0.83; P < .0001), men (aHR, 0.94; P = .0131), White patients (aHR, 0.90; P < .0001), and patients with better glycemic control with A1c levels between 5% and 6.49% (aHR, 0.91; P = .0212).
• Among patients who used SGLT2 inhibitors, the use of medicines such as insulin, sulfonylureas, antiepileptics, and sedatives was also associated with a significantly reduced risk for delirium (P < .05 for all).

IN PRACTICE:

“By leveraging real-world data on an unprecedented scale, this study not only bridges a critical knowledge gap but also paves the way for a paradigm shift in first-line diabetes management, prioritizing both metabolic and neurocognitive health,” the study authors wrote.

SOURCE:

This study was led by Mingyang Sun and Xiaoling Wang, Department of Anesthesiology and Perioperative Medicine, People’s Hospital of Zhengzhou University, Henan Provincial People’s Hospital in Zhengzhou, China. It was published online in Diabetes Care.

LIMITATIONS:

The researchers relied on diagnostic codes which may have missed milder cases of delirium, especially those managed outside hospital settings. The presence of residual confounding factors could not be completely ruled out. Information on neurocognitive markers was absent, which restricted the understanding of the neuroprotective effects of SGLT2 inhibitors.

DISCLOSURES:

This study was supported by grants from National Key Research and Development Program of China, National Natural Science Foundation of China, and Lo-Hsu Medical Foundation, Lotung Poh-Ai Hospital. The authors reported having no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.