Effects of Empagliflozin and Lifestyle Intervention on Improving Body Weight and Other Metabolic Parameters in Atypical Antipsychotics-treated Patients with Schizophrenia Spectrum Disorders—A Double-blind Randomized Placebo-controlled Trial

BACKGROUND AND HYPOTHESIS: Patients with schizophrenia spectrum disorders have elevated cardiovascular risk with obesity and deranged metabolic profiles associated with antipsychotic usage, bearing significant tolls on chronic morbidity and mortality. The present study aims to evaluate the efficacy and tolerability of sodium-glucose co-transporter 2 inhibitors (SGLT2i) in improving weight control and metabolic profile in atypical antipsychotics-treated patients with schizophrenia spectrum disorders. STUDY DESIGN: This double-blind, randomized, placebo-controlled trial studied overweight or obese adults with schizophrenia spectrum disorders (non-diabetic or pre-diabetic) who were taking atypical antipsychotics. Participants recruited from a specialist clinic of a regional public service were randomized to receive empagliflozin or placebo for 16 weeks, in combination with standardized lifestyle intervention through psychoeducation. The primary outcomes were changes in body weight and body mass index (BMI). Changes in other metabolic parameters were examined as secondary outcomes. Linear mixed models were used to study the differences in outcomes between the active and placebo arms. RESULTS: Of the 52 patients undergoing randomization, the SGLT2i group had significant reductions in body weight (-1.53 kg; 95% CI, -2.60 to -0.47), BMI (-0.53 kg/m2; 95% CI, -0.91 to -0.15), fasting glucose (-0.40 mmol/L; 95% CI, -0.65 to -0.15), and glycated hemoglobin A1c (-0.11%; 95% CI, -0.21 to -0.02) compared with the placebo group (P-values