Pharmacotherapy as a therapeutic option

Abstract

Obesity is a chronic and progressive disease that requires sustained and individualized therapeutic strategies. Both pharmacotherapy and metabolic bariatric surgery (MBS) act on the mechanisms that regulate hunger and satiety through the gut-brain axis and, in addition to weight loss, generate cardio-renal-metabolic, hepatic, mechanical and functional benefits.

The development of potent new drugs such as nutrient-stimulated hormones (NuSH) has progressively reduced the gap with respect to the efficacy of MBS in the treatment of obesity. Drugs achieve weight reductions that were previously only achieved with surgery and have shown benefits in several obesity-related diseases, such as T2DM, MASLD, HFpEF, kidney disease, OSA and knee OA.

However, real-world results differ from RCT data. The use of drugs requires long-term adherence and must be associated with lifestyle changes to achieve maximum benefits. There are important barriers to this, such as tolerance to adverse effects, adherence, and the ability to sustain the high cost in the long term. Drugs require chronic administration to maintain their effects; their discontinuation is associated with weight regain and loss of the metabolic benefits achieved.

For the moment, the magnitude of weight loss continues to be greater with MBS, and we still do not have evidence with drugs in patients with severe obesity (BMI > 50 kg/m2). There is more data on surgery in the long term since the use of potent new drugs has been around for less than a decade.

The same concerns that exist with large weight losses with surgery exist for drugs: potential micronutrient deficits, unfavorable changes in body composition (sarcopenia/osteopenia) and development of gallstones.

In this context, drugs and surgery should not be considered opposing strategies. Both can be used at different times during the course of the disease, integrated or sequenced throughout the individual trajectory of the patient. The choice should consider the severity of obesity, the clinical and metabolic phenotype, comorbidities, weight trajectory, response to previous treatments, tolerability, accessibility, and fundamentally, patient preferences. The dichotomy MBS vs drugs should be reformulated towards a sequential and complementary treatment scheme, according to the individual needs of each patient at the appropriate time.