Abstract
BackgroundSodium–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.MethodsWe 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.ResultsThe patients’ baseline body mass index (BMI) was 28.08 pm 4.88 kg/m2. SGLT2i treatment was associated with a BW loss of 1.35 pm 3.28 kg (1.78%pm 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 ge 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 ge 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 ge 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 ge 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).ConclusionBW 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.
Highlights
Sodium–glucose cotransporter 2 inhibitor (SGLT2i) use reduces body weight (BW) in patients with type 2 diabetes mellitus (T2DM)
The main findings of this study are as follows: (i) Baseline body mass index (BMI) ≥ 27.5 kg/m2 is independently associated with a significantly increased risk of new-onset atrial fibrillation (AF) in patients with T2DM treated with SGLT2i. (ii) A ≥ 5% reduction in BW after 12-week SGLT2i treatment is independently associated with a significantly lower new-onset AF risk in these patients. (iii) The benefit of a ≥ 5% BW loss associated with SGLT2i treatment in reducing AF risk persisted across all T2DM subgroups, irrespective of underlying comorbidities, baseline BMI, or Diabetes mellitus (DM) status (P for interaction > 0.05). (iv) By contrast, neither baseline BMI nor posttreatment BW loss predicted the risk of major adverse cardiovascular events (MACE)/heart failure (HF) in patients with T2DM treated with SGLT2i
In contrast to the impact of new-onset AF, our study demonstrated that neither baseline BMI nor BW loss after SGLT2i treatment affected the risk of MACE/ HF hospitalization in patients with T2DM treated with SGLT2i
Summary
Sodium–glucose cotransporter 2 inhibitor (SGLT2i) use reduces body weight (BW) in patients with type 2 diabetes mellitus (T2DM). Whether BW loss following SGLT2i treatment reduces AF risk in patients with T2DM remains unclear. Post hoc analysis of the DECLARE-TIMI 58 trial and a few real-world data indicated that the use of dapagliflozin and other SGLT2is was associated with a lower new-onset AF/atrial flutter risk than current standard care of antihyperglycemic agents in patients with T2DM [9, 10]. SGLT2is directly cause body weight (BW) loss through glucose excretion (calorie loss); how BW loss affects new-onset AF risk in patients with T2DM remains unclear. This study, by using a large real-world database of an Asian population with T2DM, evaluated whether BW loss due to SGLT2i treatment reduces the risk of new-onset AF
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