“Nothing inspires more reverence and awe in me than an old man who knows how to change his mind.”
—Santiago Ramón y Cajal
The emergence of the second and third generations of effective drugs for the treatment of obesity represents the beginning of a new era in the management of one of the most prevalent diseases in our environment. In many ways, this likely represents a paradigm shift. The indications for each modality, criteria for evaluating their efficacy, therapeutic strategies and logistics, and even the definition of obesity itself have all changed thanks to a better understanding of its pathophysiology and the experience accumulated over years of treatment. However, what has become clear is the need for an evidence-based multidisciplinary approach that is appropriate for the needs and resources of our environment.1
In contrast to the long-term efficacy demonstrated in numerous clinical trials of an increasingly safe surgery that can only be offered to 1%–2% of the population at risk, a group of active ingredients has emerged that offers weight loss close to 20% of total weight and a notable improvement in comorbidities, such as type 2 diabetes or liver dysfunction associated with metabolic syndrome, as well as a decrease in overall cardiovascular risk.2 Although surgery continues to offer better results, its consideration as the sole and indisputable option seems difficult to defend. From a simplistic point of view, it could be said that these drugs are the logical alternative to surgery and that the latter will remain a residual option for more serious cases or failures of the treatment erroneously called “conservative”. This same perspective could lead us to state that pharmacological treatment (PT) may not be sufficient or last over time. We must not forget that the best results of both options have been obtained in clinical trials, with highly controlled environments and demanding follow-up protocols. Recent publications indicate that the results of pharmacological treatment in “real-world studies” are different.3 Furthermore, a set of surgical techniques with very diverse metabolic effects and a group of drugs that act only on the multiple molecules involved in the very complex pathophysiology of obesity converge. Thus, it is necessary to accept (as already observed with surgery, and now observed with pharmacological treatment) that the rate of individual variability of response is not negligible, and any prediction of results with current tools is uncertain at the very least.4
Currently, these drugs are being used indiscriminately beyond their theoretical indications, without taking measures to improve lifestyle or reliable records regarding their safety and efficacy. The actual rate of discontinuation of medication due to both undesirable effects and (mainly) the inability to afford the cost is not known, but it seems quite high.5
The current context of obesity treatment is one of confrontation in which beliefs and devotion prevail over scientific evidence and, evidently, over the needs of individuals with obesity. In the era of patient-centered medicine, we are losing perspective because, first of all, what we know about the disease itself is changing. When evaluating which treatment is most appropriate for a patient, we must accept the end of the “barocentric” approach to the disease and instead consider the activity of the visceral adipose tissue, which induces a chronic low-grade inflammatory state, as the main defining feature of obesity. However, for now there is no simple and feasible way to determine this parameter. Thus, at the threshold of the decline of body mass index as basically the only factor to indicate obesity treatment, the consideration and weighting of other anthropometric parameters (hip/waist circumferences), direct or indirect measurements of active adipose mass, or different biomarkers will be the tools that we will use to prescribe treatments and evaluate the results and evolution of our patients.6
The sometimes indiscriminate and unilateral prescription of current GLP-1 agonists as well as dual-action drugs (GLP-1/GIP), new molecules and their combinations (retatrutide, cagrisema, survodutide, orforglipron, etc) has been received by the scientific community and general society with unusual enthusiasm; to date, the media impact is still unknown. However, this enthusiastic response has ignored relevant factors, such as problems with its cost, availability, contraindications (e.g., family history of medullary thyroid carcinoma) and, fundamentally, the need for indefinite treatment in order to maintain acceptable weight loss. In studies of proven quality, such as the “STEP” or “SURMOUNT” series, the withdrawal of GLP-1 agonists has correlated with systematic weight regain.7,8 Also, no drug in this group has demonstrated the same efficacy when it is administered again after a period of suspension. This same problem had already been observed with revision surgery for the management of weight regain (except in cases where a supposed new mechanism of action was ideally added), as the results have been disappointing. It is very likely and desirable that the use of drugs will greatly reduce the indication of second surgeries in non-responders or weight regain. Studies are beginning to appear in which adding GLP-1Ra improves these situations, with promising results. In other words, there is now the possibility of “adjuvant” therapy for obesity.9 Thus, it seems logical (and until now it had been done intuitively) to think of “neoadjuvant” therapy with drugs before surgery or even strategies to escalate or de-escalate treatments on an individual basis. It does not seem sustainable to propose treatment regimens without considering all the options: the consequences of a poorly indicated surgery are unacceptable, just like it is unacceptable to delay surgery when it is known in advance that the beneficial effect of PT will not be sufficient given the characteristics of the patient’s obesity. Likewise, this wide range of possibilities should fit into a context of constant multidisciplinary communication and adequate information for the patient. The patient must be made aware of all therapeutic options and their expected results. Only in this manner can the decision-making process be shared.
Given the current context of obesity treatment, the dynamics implemented in multidisciplinary committees and units must evolve. As surgeons, we must take a step forward and participate from the initial therapeutic decision, getting involved in the management of these patients beyond the confirmation of the indication, choice of a technique, or identification and treatment of complications and unsatisfactory results. We need to admit that the complexity of obesity requires more detailed and complex analysis for decision-making and accept that many patients will benefit from an initial PT, proposing reasonable consensual strategies when this is not sufficient or surgery does not provide the expected results.10 It is time to face the challenge of surgical treatment of obesity from the profound understanding of its pathophysiology and therapeutic alternatives, careful indication, excellent execution and consideration of all viewpoints of all parties who only seek to benefit the patient.
Declaration of Generative AI and AI-assisted technologies in the writing processNo artificial intelligence tools were used to write this manuscript.
