Initiation of New Glucose-Lowering Therapies May Act to Reduce Physical Activity Levels: Pooled Analysis From Three Randomized Trials

OBJECTIVE Sodium–glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide 1 receptor agonists (GLP-1RA) reduce body weight and improve cardiometabolic health, but their effect on physical activity is unknown. RESEARCH DESIGN AND METHODS We pooled data (n = 148) from three randomized trials to investigate the effect of empagliflozin (SGLT2i) and liraglutide (GLP-1RA), in comparison with sitagliptin (dipeptidyl peptidase 4 inhibitor) and dietary therapies, on accelerometer-assessed physical activity. RESULTS Liraglutide (mean 21,144 steps/day; 95% CI 22,069 to 2220), empagliflozin (21,132 steps/day; 21,739, 2524), and sitagliptin (2852 steps/day; 21,625, 278) resulted in reduced total daily physical activity after 6 months (P < 0.01 vs. control). Moderate-to vigorous-intensity physical activity was also reduced. Dietary interventions led to no change or an increase in physical activity. CONCLUSIONS The initiation of all glucose-lowering therapies was associated with reduced physical activity, warranting further investigation.