Prior SGLT2 Inhibitor and Metformin Use and Risk of Long COVID in Type 2 Diabetes: A Nationwide Population-Based Cohort Study.

Abstract

Introduction: Patients with type 2 diabetes mellitus (T2DM) are at increased risk of post-acute sequelae after COVID-19 (PASC). Sodium-glucose cotransporter-2 inhibitors (SGLT2i) and metformin may have systemic benefits beyond glycemic control. We evaluated the impact of prior SGLT2i and metformin use on the risk of post-acute COVID-19 complications.

Methods: We conducted a retrospective, population-based cohort study using national healthcare claims databases, from July 1, 2021 to February 28, 2023. Cohorts were stratified based on SGLT2i or metformin, against patients had not received these medications. Overlap weighting was applied to adjust for baseline differences in demographics, vaccination status, comorbidities, and prior healthcare utilization. Competing-risks regression models were used to assess differences in the risk of long-COVID outcomes between 31 and 300 days post-infection.

Results: Among 71,698 patients with T2DM, 22,501 (31.4%) had prior SGLT2i use, and 66,792 (93.1%) had prior metformin use. Compared with non-SGLT2i users, patients treated with SGLT2i had a significantly lower risk of neurological sequelae (aHR = 0.60 [0.45-0.81]), particularly memory and cognitive impairment (aHR = 0.63 [0.41-0.98]). SGLT2i was also associated with a reduced risk of post-acute symptoms (aHR = 0.87 [0.77-0.99]). Metformin use was associated with significantly lower risk of composite post-acute outcomes (aHR = 0.80 [0.68-0.96]) and post-acute symptoms (aHR = 0.77 [0.63-0.93]). Amongst patients on metformin, the addition of SGLT2i further lowered the risk of neurological sequelae (aHR = 0.81 [0.71-0.93]) and composite symptoms (aHR 0.87 [0.76-0.99]).

Conclusion: SGLT2i and metformin use were associated with a lower risk of PASC and post-acute symptoms. There may be additional protective benefits when both agents are used concurrently.