Very low-calorie ketogenic diet and liraglutide as a synergistic strategy for the treatment of obesity: A short-term, non-randomised, observational, real-world clinical evaluation

Obesity is a complex condition influenced by a combination of genetic, environmental, and behavioral factors, and it significantly impacts overall health. The management of obesity requires an integrated approach, with dietary therapy as its cornerstone. Among nutritional strategies, the Very Low-calorie Ketogenic Diet (VLCKD) has gained attention for its ability to induce rapid weight loss while minimizing lean mass loss and enhancing satiety. However, for many patients, dietary interventions alone often fall short in achieving sustainable long-term results. In this context, GLP-1 receptor agonists have demonstrated efficacy in reducing and maintaining body weight through appetite modulation and improved glycemic control long term. This single-center, prospective observational study evaluated the efficacy and safety of VLCKD alone (VLCKD group) compared to its combination with liraglutide (VLCKD+Lira group) over a four-month observation period. Both strategies resulted in significant reductions in body weight and improvements in metabolic parameters. However, the VLCKD+Lira group experienced greater weight loss (p=0.013) and a more pronounced reduction in insulin resistance (p<0.001). Ketone levels were higher in the combination group, suggesting improved adherence to the dietary regimen. Despite the metabolic benefits, the VLCKD+Lira group reported a higher incidence of adverse effects, including nausea (p<0.001), heartburn (0.004), reflux (p=0.009), and mental and physical fatigue (p=0.003 and p=0.02, respectively). Safety parameters, including liver enzymes and renal function, remained stable in both groups. These findings suggest that the combination of VLCKD and liraglutide represents an effective strategy for obesity management, although the increased incidence of adverse effects necessitates careful clinical monitoring.