Summary: Rapid advances in pharmacotherapy for obesity and type 2 diabetes now offer patients with these conditions a better chance of achieving their target body weight and blood glucose levels. This significantly reduces the risk of complications and improves quality of life. Incretin receptor agonists (glucagon-like peptide-1 (GLP-1) receptor analogues and the dual agonist of GLP-1 and glucose-dependent insulinotropic peptide receptor (GIP) – tirzepatide) are the first-line treatment for many patients with obesity and/or type 2 diabetes due to their proven cardiometabolic benefits. However, despite their unquestionable advantages and established position in the treatment of metabolic diseases, incretin receptor agonists are not a universal solution for all patients, particularly when the priority is addressing overweight and obesity. This is because obesity is a complex disease and its effective treatment requires consideration of the various mechanisms that contribute to weight gain. In such situation, an effective solution is to add naltrexone in combination with bupropion to existing therapy. This combination is also effective in patients who are intolerant to incretin receptor agonists, as well as in cases of obesity recurrence following previous treatment. An additional advantage of using naltrexone and bupropion to treat obesity and overweight is the positive impact it has on body composition and patients' quality of life.