The impact of weight loss related to risk of new-onset atrial fibrillation in patients with type 2 diabetes mellitus treated with sodium–glucose cotransporter 2 inhibitor

Background: Sodium–glucose cotransporter 2 inhibitor (SGLT2i) use reduces body weight (BW) in patients with type 2 diabetes mellitus (T2DM). Obesity and T2DM are strong risk factors of new-onset atrial fibrillation (AF). However, whether BW loss following SGLT2i treatment reduces AF risk in patients with T2DM remains unclear. Methods: We used a medical database from a multicenter health care provider in Taiwan, which included 10,237 patients with T2DM, from June 1, 2016 to December 31, 2018, whose BW data at baseline and at 12 weeks of SGLT2i treatment were available. Patients were followed up from the drug index date until the occurrence of new-onset AF, discontinuation of the SGLT2i, or the end of the study period, whichever occurred first. Results: The patients’ baseline body mass index (BMI) was 28.08 ± 4.88 kg/m². SGLT2i treatment was associated with a BW loss of 1.35 ± 3.28 kg (1.78%± 4.47%). There were 37.4%, 47.0%, and 15.6% of patients experienced no-BW loss (n = 3832), BW loss 0.0–4.9% (n = 4814), and ≥ 5.0% (n = 1591) following SGLT2i treatment, respectively. Compared with patients with baseline BMI < 23 kg/m², AF risk significantly increased in patients with baseline BMI ≥ 27.5 kg/m² (P for trend = 0.015). Compared with those without BW loss after SGLT2i treatment, AF risk significantly decreased with a BW loss of ≥ 5.0% (adjusted hazard ratios [95% confidence intervals]: 0.39[0.22–0.68]). Use of diuretics, old age, high-dose SGLT2i, higher estimated glomerular filtration rate, and baseline BMI were independent factors associated with a BW loss of ≥ 5.0% following SGLT2i initiation. By contrast, neither baseline BMI nor BW loss after SGLT2i treatment predicted major cardiovascular adverse events or heart failure hospitalization risk (P for trend > 0.05). Conclusion: BW loss of ≥ 5.0% following SGLT2i treatment was associated with a lower risk of new-onset AF in patients with T2DM in real-world practice.