The rapid rise of glucagon-like peptide-1 receptor agonists, or GLP-1 RAs, is transforming the treatment of obesity—and exposing a problem that medicine has struggled to solve for decades. These drugs can reduce appetite, alter food-reward pathways and improve several cardiometabolic measures, including blood-glucose control and cardiovascular risk factors. Their popularity has surged across clinical practice, private health services and, increasingly, self-directed online markets. But a new commentary in BMC Medicine argues that the medication revolution will not deliver its full promise unless it is paired with sustained psychological, behavioral and social support. Brunna Boaventura of the Federal University of Santa Catarina in Brazil and Stuart W. Flint of the University of Leeds in the UK warn that prescribing medication without helping people build durable behavior-change skills could create a modern version of an old mistake: treating body weight as an isolated problem rather than as one part of a complex chronic disease.

The authors’ central message is not that lifestyle interventions should replace medication. Instead, they argue that obesity care must become genuinely multimodal, combining pharmacological treatment with structured behavioral support and, when appropriate, psychological, nutritional, medical and surgical care. The World Health Organization recognizes obesity as a chronic, relapsing disease, meaning that long-term management is often necessary even after substantial weight loss. Yet in routine healthcare, behavioral treatment is frequently reduced to brief advice—“eat better,” “exercise more” or “monitor your weight”—rather than delivered as a continuous clinical service. That implementation gap has several causes: many clinicians receive limited training in behavior-change techniques, referral routes to dietitians, psychologists and health coaches may be weak, reimbursement is often inadequate, and healthcare systems rarely account for the social and structural conditions that shape daily choices. The result is a mismatch between the biological complexity of obesity and the simplicity of the support many patients receive.

GLP-1 RAs make that mismatch more consequential because their benefits are closely tied to continued treatment and individual response. The drugs mimic or enhance signaling by hormones involved in appetite regulation and glucose metabolism. By activating GLP-1 receptors, they can slow gastric emptying, increase feelings of fullness and reduce food intake; their metabolic effects can also improve glycemic control. But these physiological changes do not automatically resolve the habits, routines, emotional triggers, social pressures or practical barriers that influence eating and physical activity. Nor do they guarantee identical outcomes for every patient. Some people respond strongly, others less so, and side effects, cost or limited availability can lead to treatment interruption. A systematic review and meta-analysis cited by Boaventura and Flint examined 37 studies involving 9,341 participants and found that weight regain after stopping obesity medication occurred faster than regain following behavioral weight-management programs, regardless of the amount of weight initially lost. The finding does not mean medication is ineffective; it shows why medication should be embedded in a plan designed for continuity and adaptation.

Behavior change is not a matter of receiving information and then demonstrating sufficient willpower. It emerges from the interaction of cognitive processes, emotions, motivation, self-regulation and the environment in which a person lives. An individual may intend to change eating patterns but face irregular work schedules, food insecurity, chronic stress, limited access to safe exercise spaces or a history of negative experiences in healthcare. Motivation itself can fluctuate, while habits are often triggered by cues that operate outside conscious awareness. Effective support therefore involves more than education. It can include collaborative goal setting, monitoring progress, identifying barriers, developing coping strategies, reinforcing self-efficacy and adjusting plans as circumstances change. Such interventions are most effective when they are person-centered: goals should reflect health, functioning and quality of life, not only the number on a scale. The authors say this broader approach is essential as drug-centered models become more common, because a prescription can influence appetite without supplying the skills and support needed to sustain health-related behaviors over years.

The commentary places weight stigma at the center of this challenge. People living with obesity frequently encounter moral judgment in clinics, workplaces, media and everyday life, where body size is often interpreted as evidence of laziness, irresponsibility or poor character. Those experiences can produce internalized weight stigma—the adoption of negative cultural beliefs about one’s own body—which is associated with distress, reduced self-confidence and disengagement from care. A clinical encounter that focuses narrowly on weight loss may unintentionally intensify the problem, particularly when treatment success is defined by a predetermined percentage of weight reduction. By contrast, addressing stigma and its consequences can improve eating self-efficacy, quality of life, treatment acceptability and patients’ ability to cope with difficult experiences. The authors argue that behavior-change support should therefore help people manage not only diet and physical activity, but also shame, discrimination, body-image concerns, fears of regain and the psychological burden of being judged.

The arrival of GLP-1 medications has produced a complicated cultural shift. On one hand, the drugs may challenge the idea that obesity is simply a failure of self-control by highlighting the roles of appetite, satiety, food reward and biological regulation. On the other hand, people who use them may still be criticized for taking what some regard as a shortcut. Research cited in the commentary suggests that GLP-1 use can influence how women with different body weights are evaluated, but the authors caution against assuming that medication automatically removes stigma. A person may lose weight and still carry years of negative self-beliefs, altered body image or anxiety about returning to a previous size. Physical change can itself require psychological adjustment, especially when identity, relationships and social treatment have been shaped by body weight. These consequences may persist even when a medication is working medically. In that sense, successful obesity care must address the lived experience of treatment rather than treating weight reduction as the sole endpoint.

Existing behavioral programs may not be broad enough for this new era. The intensive behavioral therapy model covered by the US Centers for Medicare & Medicaid Services emphasizes diet, physical activity and self-monitoring, with delivery largely centered on physicians and nurses and success commonly tied to weight-loss thresholds. Those components can be useful, but Boaventura and Flint argue that a weight-centered framework overlooks outcomes that matter to patients and health systems, including cardiometabolic health, mobility, mental well-being, quality of life and quality-adjusted life years. It may also fail to include professionals with specialized expertise in counseling, psychology, nutrition and sustained coaching. A broader model would measure whether people can maintain beneficial routines, manage distress, participate more fully in daily life and reduce health risks—even when weight loss is modest or fluctuates. This distinction is scientifically important because body weight is only one observable outcome of a treatment, while metabolic health and psychological functioning may change along different trajectories.

The risks become sharper when access to regulated care is limited. Demand, cost and shortages have encouraged some people to seek GLP-1 RAs through online sellers, private services or self-directed pathways. Such routes can separate medication access from clinical assessment, dose monitoring, side-effect management and follow-up. They may also expose patients to counterfeit or falsified products, inappropriate prescribing and fragmented care. When obtaining the drug becomes the primary objective, behavioral and psychosocial support can be treated as optional extras rather than essential parts of treatment. The authors do not suggest that every patient must receive an identical package of services, but they insist that safe care requires more than dispensing a medication. Patients need reliable information, supervision and access to appropriately trained professionals who can help them respond to changing appetite, adverse effects, treatment interruptions and the possibility of weight regain. Regulation, they argue, should focus not only on the products themselves but also on whether the surrounding service provides comprehensive care.

The policy implications extend beyond individual consultations. Multidisciplinary obesity treatment is widely recommended, yet it remains difficult to obtain in both public and private systems. Public-health programs need investment so that integrated services are available beyond specialist centers, while private care must confront the financial barriers created when several professionals and an expensive medication are combined. Health systems and regulators should ensure that obesity services include behavioral, psychological and social support, rather than allowing pharmacotherapy to become a substitute for chronic-care infrastructure. The authors describe this as an opportunity to redesign obesity treatment around empowerment and long-term health. GLP-1 RAs may be powerful tools, but they cannot by themselves teach people how to navigate stigma, stress, disrupted routines or the emotional consequences of bodily change. The future of obesity medicine, the commentary concludes, will be determined not simply by how many people receive these drugs, but by whether healthcare can surround them with the sustained, person-centered support required to make improvement safer and more durable.

Bariatric surgery, despite its demonstrable efficacy in promoting weight loss and ameliorating obesity-related comorbidities, is not a silver bullet. Patients embarking on this surgical path often encounter multifaceted challenges that span from psychological barriers to behavioral inconsistencies, which can undermine the surgery’s benefits if left unaddressed. Among these hurdles, exercise adherence emerges as a critical factor, intricately linked with both physical recovery and sustainable weight management. The scoping review meticulously delves into modifiable psychological processes—those cognitive and emotional variables amenable to intervention—that potentially determine how consistently patients engage with prescribed physical activity regimens.

A standout aspect of the review is its methodological rigor, following the JBI (Joanna Briggs Institute) protocol to ensure a systematic and exhaustive examination of the literature. Researchers assessed a wide range of databases, encompassing EMBASE, Scopus, Web of Science, PubMed, Cochrane Library, Physiotherapy Evidence Database (PEDro), PsycINFO, LILACS, and even grey literature sources such as Google Scholar. This breadth of inquiry allowed for a rich and nuanced synthesis of findings from diverse populations and clinical contexts. The studies analyzed targeted adults of both sexes with obesity, all of whom were enrolled in perioperative intervention programs—a critical period where behavioral modifications can yield outsized benefits.

From this rigorous review, seven studies were identified that directly address the psychological contributors to exercise adherence in bariatric surgery candidates. These psychological elements were distilled into several core constructs: quality of life, pleasure derived from exercise, intrinsic motivation, self-efficacy beliefs, self-monitoring practices, goal-setting behaviors, and proactive information seeking. Each of these factors interacts in complex ways to either promote or hinder the patient’s commitment to physical activity during the preoperative phase. For instance, individuals who perceive exercise as pleasurable or rewarding tend to exhibit better adherence, highlighting the importance of fostering positive affective experiences within rehabilitation programs.

Motivation and self-efficacy—the belief in one’s capacity to execute specific behaviors—emerge as particularly salient drivers of exercise engagement. These constructs are rooted in well-established psychological theories such as Self-Determination Theory and Social Cognitive Theory, which emphasize autonomy, competence, and relatedness as key motivators for sustained behavior change. Interventions that enhance patients’ confidence in their ability to perform physical activity, and that help them internalize the value of exercise beyond mere obligation, are crucial for long-term adherence. The review suggests a paradigm shift from prescriptive exercise protocols toward empowering, patient-centered counseling.

Cognitive-behavioral therapy (CBT) surfaced as an effective intervention modality within the reviewed studies. By addressing maladaptive thoughts, enhancing problem-solving skills, and reducing exercise-related anxieties, CBT helps individuals overcome common psychological barriers to activity. This therapeutic approach can be delivered in both individual and group formats, leveraging social support mechanisms while tailoring strategies to individual challenges. Moreover, the inclusion of motivational interviewing techniques complements CBT by fostering patient ambivalence resolution and strengthening commitment to change.

Another innovative dimension explored in these studies involves the deployment of digital technologies to optimize exercise adherence. Remote and digital platforms offer promising avenues for delivering real-time feedback, self-monitoring tools, and interactive goal-setting features. Mobile apps, wearable devices, and telehealth services can extend the reach of physical therapy support beyond clinical settings, providing continuous encouragement and accountability. The integration of these technologies within prehabilitation programs aligns with the growing movement toward personalized medicine and patient empowerment, offering scalable solutions that transcend geographic and socioeconomic barriers.

While the psychological determinants identified are critical, the review emphasizes that successful prehabilitation programs must adopt a multi-theoretical approach. This necessitates the amalgamation of various behavioral and psychological frameworks to address the spectrum of factors influencing exercise adherence. Tailoring interventions to the unique needs, preferences, and psychosocial contexts of surgical candidates ensures higher relevance and engagement. Such customization also accounts for demographic variables such as age, sex, cultural background, and baseline fitness, which modulate patients’ responses to therapeutic strategies.

The notion of quality of life as a motivating factor warrants special attention, as it encapsulates both physical and psychological well-being. Patients who experience improvements in mood, energy levels, and social functioning as a result of exercise are more likely to maintain these behaviors. Therefore, rehabilitation efforts should not solely prioritize physical metrics but also assess and enhance subjective quality of life indices. Encouragingly, some studies document increases in enjoyment and pleasure derived from physical activity, suggesting that redesigning exercise prescriptions to maximize these positive experiences could be a game changer in preoperative care.

Goal setting and self-monitoring are integral behavioral techniques that empower patients to take ownership of their activity patterns. By establishing clear, attainable objectives and systematically tracking progress, patients cultivate a sense of achievement and control. These processes also generate vital data that clinicians can use to tailor interventions responsively. Digital platforms are particularly adept at facilitating these activities, offering user-friendly interfaces for logging exercise sessions, setting reminders, and analyzing trends over time.

Information seeking emerges as another psychological variable with notable implications. Patients actively engaged in gathering knowledge about the benefits of exercise, surgical outcomes, and rehabilitation protocols tend to demonstrate higher adherence. This underscores the importance of educational components within prehabilitation programs, where providing transparent, evidence-based information can dispel misconceptions and reduce anxiety surrounding surgery and physical activity.

An overarching theme in the review is the necessity of embedding physical activity counseling within a holistic rehabilitation framework. Physical therapists, equipped with knowledge of psychological determinants, are optimally positioned to lead these multidisciplinary efforts. Their expertise in exercise prescription, combined with counseling skills and familiarity with behavioral change techniques, positions them as pivotal agents in enhancing pre-surgical fitness and psychological readiness.

Finally, the adoption of remote digital technologies preoperatively is increasingly viewed as not only feasible but essential in modern healthcare delivery. These modalities can reduce barriers related to distance, time constraints, and mobility limitations that often restrict patient participation in traditional rehabilitation programs. Moreover, by complementing face-to-face interactions with sustained virtual support, they foster continuity of care and facilitate the maintenance of behavioral gains.

In summary, the scoping review illuminates the intricate interplay of psychological determinants that influence exercise adherence among individuals preparing for bariatric surgery. By embracing multi-faceted and theory-driven interventions—ranging from cognitive-behavioral therapies and motivational counseling to digital health innovations—physical therapy prehabilitation programs can profoundly enhance treatment efficacy. As obesity rates continue to climb globally, refining these approaches will be crucial in optimizing surgical outcomes and fostering sustainable health improvements.

Subject of Research: Psychological determinants of exercise adherence in individuals with severe obesity awaiting bariatric surgery and physical therapy intervention strategies in prehabilitation programs.

Article Title: Psychological determinants of exercise adherence in individuals with severe obesity awaiting bariatric surgery: what strategies can physical therapists adopt in prehabilitation programs? A scoping review.

Article References:
Nascimento, A.Q., Matte, D.L., Dantas, D.B. et al. Psychological determinants of exercise adherence in individuals with severe obesity awaiting bariatric surgery: what strategies can physical therapists adopt in prehabilitation programs? A scoping review. Int J Obes (2025). https://doi.org/10.1038/s41366-025-01830-5

Image Credits: AI Generated

DOI: https://doi.org/10.1038/s41366-025-01830-5

Tirzepatide and semaglutide belong to a class of compounds that engage the GLP-1 receptor, with tirzepatide functioning as a dual agonist targeting both GLP-1 and GIP receptors. These agents have revolutionized the pharmacological management of obesity by significantly reducing appetite and improving glucose homeostasis, yet their influence on energy expenditure—the amount of energy the body burns over time—was less clearly understood prior to this investigation. Clarifying these effects is critical, as sustainable weight loss depends not only on caloric intake reduction but also on maintaining or enhancing metabolic rate to prevent weight regain.

In this state-of-the-art study, a cohort of 24 mice was subjected to a prolonged high-fat diet designed to induce obesity before dividing them into three groups for intervention: a control group receiving no pharmacological treatment, a semaglutide-treated group, and a tirzepatide-treated group. Both drug-treated groups received daily dosages of 10 nmol/kg for four consecutive weeks, followed by a washout period of two weeks wherein treatment was halted but the high-fat diet was maintained. This experimental design enabled researchers to observe both the acute drug effects and any lasting metabolic adaptations that persisted after cessation.

One of the critical innovations of this work was the use of indirect calorimetry to continuously monitor energy expenditure in real-time. This technique, which quantifies oxygen consumption and carbon dioxide production, allows precise estimation of whole-body energy utilization. Conducting the experiments at thermoneutrality further controlled environmental variables, eliminating the confounding effects of cold-induced thermogenesis, thus ensuring that changes in metabolic rate were drug-related rather than a response to ambient temperature stress.

Remarkably, mice treated with tirzepatide displayed a substantial increase in energy expenditure as early as four days into the regimen. This elevated metabolic rate was sustained through the second week of treatment before gradually declining to baseline levels. Intriguingly, these changes were not linked to increased locomotor activity, suggesting a direct pharmacological effect on metabolic tissues rather than behavioral changes. On the other hand, semaglutide treatment resulted in a pronounced initial decrease in energy expenditure during the first three days, reflecting a transient metabolic slowdown during weight loss.

Body weight changes mirrored these metabolic shifts. Control animals experienced modest weight gain over the treatment period, averaging a 2.7-gram increase. In stark contrast, tirzepatide-treated mice lost an average of 15.6 grams, while semaglutide-treated mice shed approximately 8.3 grams. Most of this weight loss occurred in the first week, coinciding with profound reductions in food intake. These data highlight tirzepatide’s superior efficacy in promoting rapid and significant weight loss, potentially attributable to its unique ability to elevate energy expenditure transiently.

The respiratory exchange ratio (RER), a parameter indicating substrate utilization, further illuminated how these drugs shift metabolic fuel preference. Both semaglutide and tirzepatide initially lowered the RER, suggesting enhanced fat oxidation and reduced reliance on carbohydrate metabolism. This metabolic adaptation supports weight loss by mobilizing fat stores to meet energy demands. However, after three weeks of continuous dosing, RER values returned to baseline, and during the washout period, they increased above control levels as animals resumed higher caloric intake, indicating a reversible effect linked to drug presence.

Dr. Simone Bossi, co-leading the study at Gubra’s Pharmacology Research department in Denmark, explained the clinical relevance: “Our findings elucidate how these drugs not only suppress appetite but exert distinct effects on energy expenditure, which are crucial for sustained weight loss. Semaglutide’s initial decrease in metabolic rate aligns with classic physiological energy conservation during calorie restriction, while tirzepatide’s transient metabolic boost may offer an advantage for weight reduction.” These mechanistic insights help explain tirzepatide’s more potent anti-obesity effects observed in clinical settings.

Critically, the cessation of treatment reversed the metabolic adaptations. During the two-week washout period, energy expenditure returned to control levels for both drug groups, and the mice increased their food consumption, ultimately nullifying prior metabolic gains. This phenomenon underscores a key challenge in obesity pharmacotherapy: maintaining long-term weight loss requires not only suppressing intake but also sustaining or enhancing energy expenditure to offset adaptive responses that favor weight regain.

These revelations pave the way for a paradigm shift in the development of obesity treatments. Current therapies primarily focus on appetite suppression, yet the transient metabolic effects suggest that augmenting energy expenditure pharmacologically could potentiate and prolong weight loss outcomes. Future investigations aimed at dissecting the molecular pathways mediating tirzepatide’s metabolic activation may uncover new targets for drug development with an emphasis on enduring metabolic elevation, thereby overcoming the body’s compensatory mechanisms.

Moreover, this research highlights the importance of timing and dosage strategies in anti-obesity drug administration. Understanding the temporal metabolic fluctuations induced by these drugs can inform treatment regimens that optimize efficacy while minimizing metabolic adaptation. Integrating metabolic monitoring tools such as indirect calorimetry in clinical settings could further personalize therapy by identifying responders and tailoring dosing schedules to individual metabolic profiles.

In summary, this pioneering study elucidates critical differences in how tirzepatide and semaglutide modulate metabolism beyond appetite suppression. Tirzepatide’s unique ability to transiently elevate energy expenditure, coupled with both drugs’ promotion of fat oxidation, contributes to robust weight loss, but these metabolic changes dissipate rapidly after treatment withdrawal. These findings underscore the dynamic interplay between pharmacology and physiology in obesity management and open exciting avenues for novel therapeutic strategies targeting sustained energy expenditure enhancement.

As obesity continues to be a global health crisis demanding effective long-term interventions, understanding and manipulating metabolic adaptations to therapy represent a promising frontier. The nuanced insights from this study not only advance scientific knowledge but also provide practical implications for improving patient outcomes. Ongoing research will undoubtedly expand on these findings to develop drugs that harness and maintain beneficial metabolic shifts, ultimately transforming the landscape of obesity treatment and chronic weight management.

Subject of Research: Metabolic adaptations and energy expenditure effects of tirzepatide and semaglutide in obesity treatment.

Article Title: Distinct Metabolic Effects of Tirzepatide and Semaglutide Uncovered in Preclinical Obesity Model.

News Publication Date: 13-May-2025

Keywords: tirzepatide, semaglutide, energy expenditure, obesity, metabolic adaptation, GLP-1 receptor agonists, weight loss, fat oxidation, indirect calorimetry, pharmacology, weight maintenance