What bariatric surgery can teach us about glucagon-like peptide-1 agonist weight loss therapy: Improving long-term outcomes and patient care

Abstract

The use of anti-obesity medications (AOMs) is rising rapidly. However, structured monitoring and support for these patients remain limited. In contrast, bariatric surgery has well-established multidisciplinary care models that address nutritional requirements, psychological screening, and long-term risk management. Bariatric surgery pathways could inform safer and more comprehensive care for individuals on glucagon-like peptide-1 receptor agonists (GLP-1RA). A literature search was conducted on MEDLINE and EMBASE Ovid, focusing on short- and long-term outcomes of bariatric surgery and pharmacological weight-loss therapies. Bariatric surgery pathways routinely incorporate nutritional monitoring and supplementation, reflecting the well-recognised risks of protein and micronutrient deficiencies. Comparable guidance for pharmacotherapy is lacking, despite similar risks. Rapid weight loss is associated with gallstone formation, with evidence supporting ursodeoxycholic acid prophylaxis in surgical patients, but evidence is lacking in pharmacotherapy Surgical care further emphasises lean mass preservation, dietary counselling, and psychological support, which are inconsistently addressed in GLP-1RA users. The growing use of AOMs highlights the need for more comprehensive care frameworks. Adopting key elements of established bariatric surgery pathways may enhance safety, improve patient education, and optimise long-term outcomes for individuals receiving AOMs.

Key Words: Bariatric surgery; Glucagon-like peptide-1 receptor agonists; Micronutrient deficiencies; Protein intake; Skeletal muscle mass; Ursodeoxycholic acid; Body image; Self-harm and suicide; Patient education; Alcohol intake

Core Tip: Obesity is a prevalent chronic disease associated with significant metabolic and psychosocial morbidity. While metabolic bariatric surgery (MBS) remains the most effective treatment, incretin-based therapies, particularly glucagon-like peptide-1 receptor agonists, are increasingly used. However, these agents are relatively new, with limited long-term data and risks related to rapid weight loss, including nutritional deficiencies, lean mass loss, and psychosocial effects-well recognised in bariatric practice. Unlike MBS, which benefits from structured follow-up and multidisciplinary care, pharmacotherapy pathways often lack equivalent monitoring and support. This review explores how bariatric principles can improve the safety and long-term outcomes of anti-obesity medication use.

INTRODUCTION

Obesity is a highly prevalent disease that is strongly associated with diabetes, cardiovascular disease, and kidney disease, with links to psychosocial burden and body dysmorphia[1,2]. The NCD risk factor collaboration global analysis has shown a general increase in obesity prevalence between 1990 and 2022[3]. The traditional, most effective treatment for obesity is metabolic bariatric surgery (MBS). However, surgery remains the last option for severe obesity if all other interventions have been trialled[4]. Since the discovery of highly potent glucagon-like peptide-1 receptor agonists (GLP-1RA) for weight loss management, the use of these medications, including liraglutide, semaglutide, and tirzepatide, has become increasingly popular[5].

The widespread use of incretin-based pharmacotherapy is not without its accompanying risks and uncertainties, given the recent approval for use in obesity management, and limited studies on the long-term effects of GLP-1RA use. Studies suggest that obesity is a chronic condition similar to other diseases (e.g., hypertension and diabetes mellitus) that require long-term therapy[6]. Studies have also shown that cessation of weight loss medications leads to relapse in weight gain[4,6].

Early bariatric experience demonstrated that rapid weight loss was frequently accompanied by loss of skeletal muscle mass, macronutrient and micronutrient deficiencies and gallstones[7]. Rapid weight loss induces nutritional deficiencies and loss of lean mass leads to unrealistic expectations from the general population, and is associated with stigma relating to bariatric surgery, body image issues and psychological maladjustment[8]. Studies also linked bariatric surgery with increased alcohol consumption[8], need for plastic surgery to deal with loose skin[9] and higher rates of self-harm and suicides[10,11]. Without structured follow-up or patient education on treatment expectations, nutrition, and diet, patients commonly experienced relapse in weight gain and nutritional deficiencies. Patients receiving incretin-based pharmacotherapies for weight loss often lack comprehensive education regarding potential risks. Furthermore, they are not consistently monitored or supported, in contrast to the structured follow-up and multidisciplinary care routinely provided to patients undergoing bariatric surgery. This creates a significant gap in service provision and may expose patients to avoidable harm.

There are many studies surrounding MBS with well-established guidelines surrounding topics of nutrition, ursodeoxycholic acid (UDCA) prophylaxis, mental health and patient education. In addition, there are well-established postoperative follow-up pathways, with clearly defined complications and management strategies for patients undergoing bariatric surgery. In contrast, comparable structured support is lacking for those receiving incretin-based weight-loss pharmacotherapy, even though many associated issues arise from significant weight loss itself and are therefore not exclusive to surgical patients.

Literature relating to medication-induced weight loss and associated long-term outcomes is limited due to the relatively recent adoption of GLP-1RA in obesity management, in contrast to the extensive evidence base for MBS, which spans over half a century. This narrative review aims to identify key lessons from current bariatric surgical practice and to explore how these insights can be applied to optimise patient care based on current literature and clinical experience.

MATERIALS AND METHODS

A narrative literature review was selected to enable a meaningful synthesis of relevant published studies while allowing scope for critical interpretation by the authors. The search was conducted using PubMed and EMBASE Ovid. Key search terms included “Bariatric surgery”, “GLP-1 receptor agonists”, “Micronutrient deficiencies”, “Protein intake”, “Skeletal muscle mass”, “Ursodeoxycholic acid”, “Body image”, “Self-harm and suicide”, “Patient education” and “Alcohol intake”. We included studies published in English from 2010 onwards. The literature search focused primarily on weight loss medications and their long-term outcomes, including physical health, mental health, body image, nutritional status, muscle mass, and patient education. We prioritized high-quality evidence, including systematic reviews, clinical guidelines, randomized controlled trials, and prospective studies.

MICRONUTRIENT AND MACRONUTRIENT SUPPLEMENTATION

Substantial weight loss is commonly associated with alterations in macronutrient intake and body composition. Current bariatric surgery guidelines consistently emphasise the importance of structured nutritional monitoring and supplementation to prevent both macronutrient (mainly protein) and micronutrient (vitamins and minerals) deficiencies during periods of rapid weight loss[12,13]. In contrast, comparable evidence guiding nutritional management in pharmacological weight-loss therapy remains limited, with no established guidelines currently available[14]. Micronutrient deficiencies are well recognised in individuals with obesity, and it is plausible that significantly reduced caloric intake-often occurring without adequate dietary education-may further compromise micronutrient consumption. This may lead to the development of new deficiencies or exacerbate pre-existing ones in patients receiving long-term obesity pharmacotherapy.

A recent scoping review[7] examining nutritional strategies in patients treated with incretin-based therapies, including semaglutide and tirzepatide, identified only twelve studies incorporating dietary interventions or nutritional assessment. Across these studies, total energy intake decreased by approximately 24%-39%, consistent with the appetite-suppressing effects of these agents. Lean mass loss accounted for up to 40% of total weight reduction. However, systematic monitoring of macronutrient intake (such as protein) was uncommon, few studies involved dietetic input, and assessment of micronutrient intake was limited, with some evidence suggesting potential nutritional inadequacies.

These findings underscore a significant gap between the nutritional effects of pharmacologically induced weight loss and the clinical frameworks designed to manage its consequences. Moreover, existing evidence remains inconsistent regarding the optimal protein intake for patients receiving GLP-1RA[15].

UDCA PROPHYLAXIS

Rapid weight loss following bariatric surgery is a well-established risk factor for gallstone formation. Factors include increased cholesterol mobilisation and reduced gallbladder motility, resulting in excess biliary cholesterol. As a result, prophylactic UDCA has been extensively evaluated in post-MBS populations.

Multiple studies support its efficacy in bariatric surgery. A randomized controlled trial by Pizza et al[16], including 110 patients, compared those who received UDCA following omega-loop gastric bypass with those who did not receive postoperative UDCA, and demonstrated a significantly lower incidence of gallstone formation in the UDCA group over 12 months of follow-up. Comparable findings have been reported in other studies evaluating outcomes following bariatric surgery[17,18]. Moreover, a 2022 meta-analysis of eleven randomised controlled trials (n = 2363) confirmed that prophylactic UDCA reduces gallstone formation, symptomatic gallstone disease, and the need for cholecystectomy after bariatric surgery[19].

In contrast, evidence supporting UDCA prophylaxis in patients receiving weight-loss pharmacotherapy remains extremely limited. The absence of studies evaluating its effect on gallstone risk, coupled with a lack of prospective data and guideline recommendations, represents a significant gap in current clinical practice. Extrapolation from bariatric literature may provide a pragmatic interim framework, but dedicated studies are needed to define the role of prophylactic strategies such as UDCA in the context of pharmacological weight loss.

RISK OF SELF-HARM AND SUICIDE

Several studies have reported an increased risk of self-harm and suicide attempts among patients undergoing bariatric surgery when compared to the general population[10,11]. This association has been observed across different bariatric procedures and appears to persist in the longer-term following surgery. Proposed contributing factors include pre-existing psychiatric comorbidities, changes in psychosocial functioning, altered body image, and potential neurobiological effects related to rapid weight loss and hormonal changes. Despite these observations, the underlying mechanisms remain incompletely understood, and the relationship is likely multifactorial.

In contrast, there is a lack of evidence assessing the risk of self-harm and suicide among patients undergoing pharmacological weight-loss therapy according to a recent systematic review and meta-analysis[20]. Existing studies have primarily focused on metabolic outcomes and weight reduction efficacy, with limited incorporation of psychiatric outcomes or long-term psychological follow-up[20]. Consequently, the impact of pharmacologically induced weight loss on mental health outcomes, including self-harm behaviours, remains uncertain and requires further investigation to ensure that potential risks, such as self-harm and suicide, are recognized and appropriately addressed. Extrapolating from bariatric literature, there is a clear need to integrate mental health screening, patient education, and ongoing psychological support into medical weight-loss treatment pathways.

EFFECTS ON BODY IMAGE

Body image disturbance, including features consistent with body dysmorphia, has been increasingly recognized following bariatric surgery. Despite significant weight loss, some patients report persistent dissatisfaction with their physical appearance, often related to excess skin, residual adiposity, or discordance between expectations and outcomes[8]. Plastic surgery is sometimes needed to deal with excess skin[9]. Studies suggest that while many individuals experience improvements in quality of life and self-esteem, a subset develop or continue to experience maladaptive body image perceptions[8]. Contributing factors are likely multifactorial and may include pre-existing psychological vulnerability, rapid physical changes, and sociocultural pressures related to body image.

In contrast, there is very limited evidence examining body image outcomes in patients undergoing pharmacological weight-loss therapy. While clinical trials of anti-obesity medications (AOMs) frequently report improvements in weight and metabolic parameters, assessment of body image and related psychological constructs are not routinely included. As a result, these effects remain poorly understood, and current evidence is insufficient to determine whether patterns comparable to those seen in bariatric populations exist

PRESERVATION OF MUSCLE MASS

Bariatric surgery patients are routinely advised to increase protein intake and engage in regular exercise to preserve lean muscle mass during weight loss according to recent guidelines[21]. However, there is inconsistency within the bariatric surgery literature regarding the optimal protein intake[22]. With the increasing use of GLP-1RAs and related combination therapies for obesity management, similar considerations are now emerging for patients treated with pharmacological weight-loss agents.

Current evidence suggests that these medications [glucagon-like peptide-1 (GLP-1)] may contribute to a reduction in lean mass[7,15,23]. A recent advisory statement reported that, in the absence of structured nutritional and exercise interventions, loss of muscle mass may account for approximately 10%-15% of total weight loss in females and 20%-25% in males[15].

To mitigate this, adequate protein intake is essential. Current recommendations for GLP-1 emphasise the consumption of low-volume, nutrient-dense protein sources such as fish, eggs, cottage cheese, nuts, seeds, and fortified products including high-protein shakes and bars. While an intake of 0.8 g/kg/day is generally advised, higher levels of 1.2-1.6 g/kg/day during active weight loss have been suggested to better preserve lean mass[15].

In addition to nutritional strategies, structured exercise programmes-particularly those incorporating resistance or strength training-are crucial in maintaining muscle mass and mitigating its loss during treatment with GLP-1RA, as recommended by a recent joint advisory[15].

PATIENT EDUCATION

Patient education is a fundamental component of bariatric surgery pathways, where individuals are counselled to develop realistic expectations regarding outcomes in order to minimise dissatisfaction and improve long-term adherence. In contrast, there appears to be a relative paucity of literature addressing structured education for patients receiving GLP-1RA and other pharmacological weight-loss therapies. This gap raises important questions regarding whether patients are adequately informed about expected outcomes, treatment duration, and potential side effects.

Emerging expert advisory statements have begun to address this need. A joint advisory[15], from the American College of Lifestyle Medicine, recommends the use of virtual education modules and coaching sessions to support patients in adopting healthy dietary habits, managing gastrointestinal side effects, and setting realistic weight-loss goals. These interventions can be complemented by structured behavioural frameworks such as the SMART approach, which may enhance adherence to nutritional, exercise, and behavioural modifications alongside medical therapy.

In addition, group-based care models such as shared medical appointments (SMAs) have shown promise in improving patient outcomes. A retrospective study from the United States demonstrated that SMAs were associated with greater weight loss compared to individual consultations, alongside improved patient satisfaction and engagement[24]. With advances in digital health, these appointments can now be delivered virtually, increasing accessibility and convenience, particularly for patients in remote or underserved areas.

Furthermore, a multidisciplinary consensus statement from Spain[25] has provided practical recommendations for patients undergoing GLP-1 therapy. These include behavioural and dietary modifications such as eating slowly, consuming smaller portions, and increasing meal frequency. Patients are also advised to tailor food intake to individual tolerance, favouring low-fat, easily digestible foods, and maintaining adequate hydration. Additional strategies are recommended for managing common gastrointestinal side effects, including nausea, vomiting, and diarrhoea, such as eating smaller, more frequent meals and ensuring sufficient fluid intake.

EFFECT ON ALCOHOL INTAKE

Bariatric surgery has been associated with an increased risk of alcohol use, with evidence suggesting a higher incidence of de novo alcohol use disorder or relapse following a period of abstinence[8]. This phenomenon is thought to result from a combination of physiological and behavioural factors, including altered alcohol metabolism and changes in reward pathways.

In contrast, emerging evidence suggests that GLP-1RA may have the opposite effect on alcohol consumption. Preclinical and clinical data indicate that GLP-1 signalling may modulate reward-related behaviours, potentially reducing alcohol craving and intake. A recent phase II, double-blind, randomised controlled trial involving 48 participants demonstrated that semaglutide significantly reduced alcohol craving and improved selected drinking outcomes[26]. Similarly, another double-blind randomised trial including 255 participants reported that the GLP-1RA dulaglutide was associated with reduced alcohol consumption in humans[27].

Together, these findings suggest that, in contrast to bariatric surgery, GLP-1RAs may decrease alcohol intake. However, further large-scale and long-term studies are required to better understand the durability of these effects and their clinical implications.

COUNSELLING REGARDING SIDE EFFECTS

Patient education regarding the risks and complications of bariatric surgery is well established and routinely delivered in a structured manner. In contrast, the extent and quality of counselling provided to patients regarding the side effects of pharmacological weight-loss therapies remain less clearly defined.

Current National Institute for Health and Care Excellence guidelines recommend that all patients with obesity receive comprehensive management, including lifestyle modification, physical activity, and behavioural interventions. The choice of pharmacological therapy is guided by body mass index and associated comorbidities, as outlined in the most recent guidance published in January 2025[28].

At present, four AOMs: Tirzepatide, Semaglutide, Liraglutide, and Orlistat-are funded within the NHS for the management of obesity through specialist weight management services. However, important uncertainties remain regarding the long-term efficacy of these agents, optimal treatment duration, side-effect profiles, and rates of weight regain following discontinuation. These gaps highlight the need for more robust evidence to support informed patient counselling, particularly for individuals considering alternatives to, or awaiting, bariatric surgery.

The side-effect profiles of AOMs vary considerably. Orlistat is commonly associated with gastrointestinal side effects such as steatorrhea, increased bowel frequency, flatus with discharge, and faecal incontinence, which are generally self-limiting[29]. In contrast, GLP-1RAs-including Liraglutide, Semaglutide, and Tirzepatide-are frequently associated with gastrointestinal symptoms such as nausea, vomiting, diarrhoea, constipation, and dyspepsia. These adverse effects may lead to treatment discontinuation, with evidence suggesting that liraglutide has one of the highest discontinuation rates among approved AOMs[30]. Additionally, GLP-1RAs have been associated with an increased risk of pancreatitis and gallbladder disease. Regulatory warnings have also highlighted a potential association with medullary thyroid carcinoma, and these agents are therefore contraindicated in patients with a personal or family history of this condition[30].

Despite the increasing use of pharmacological therapies for obesity, it remains unclear whether patients receive adequate counselling regarding their risks and side effects. Further research is required to evaluate the quality of patient education in this context and to determine its impact on treatment adherence, patient satisfaction, and clinical outcomes.

WEIGHT REGAIN AFTER STOPPING MEDICATIONS

Patients are routinely counselled about the risk of weight regain following weight loss interventions. However, less emphasis is placed on discussing the potential for weight regain after cessation of AOMs or on the expected duration of therapy. This represents an important gap in patient education, particularly as pharmacotherapy for obesity is increasingly used as a long-term strategy.

A recent systematic review and meta-analysis evaluating total body weight loss (TBWL) after 52 weeks of AOM therapy demonstrated variable efficacy across different agents. When adjusted for placebo effect, the median placebo-subtracted weight loss was 3.1% for orlistat, 4.5% for liraglutide, 11.9% for semaglutide, and 16.2% for tirzepatide. Notably, only semaglutide and tirzepatide achieved a placebo-subtracted weight loss exceeding 10%, highlighting their superior efficacy compared to earlier agents[31].

Longer-term follow-up at two years showed attenuation of this effect. Placebo-subtracted TBWL was reported as 3.0% for orlistat, 4.2% for liraglutide, and 8.7% for semaglutide, suggesting partial weight regain or plateau over time despite continued or prior therapy[31].

Weight regain following discontinuation of GLP-1RAs and related agents has emerged as a significant clinical concern. A randomized multicentre trial by Aronne et al[6] demonstrated that cessation of tirzepatide after 36 weeks resulted in regain of approximately 53% of the weight loss 52 weeks after stoppage of treatment. Similarly, a multicentre trial by Wilding et al[32] reported that participants regained approximately two-thirds of their lost weight within one year of discontinuing once-weekly subcutaneous semaglutide 2.4 mg, despite concurrent lifestyle interventions.

Collectively, these findings suggest that the benefits of AOMs are closely tied to continued use, and that discontinuation is associated with substantial weight regain. This reinforces the concept of obesity as a chronic, relapsing disease requiring long-term management, and highlights the need for clearer patient counselling regarding treatment duration and expectations after cessation.

CONCLUSION

The expanding use of GLP-1RAs marks a significant shift in obesity management, yet current care pathways remain largely focused on weight loss efficacy rather than long-term outcomes. Evidence from bariatric surgery demonstrates that substantial weight loss is associated with important nutritional, metabolic, and psychological risks that require structured, multidisciplinary management.

Applying these established principles-particularly around nutritional monitoring, muscle preservation, patient education, and long-term follow-up-offers a practical framework to improve the safety and durability of pharmacological weight-loss therapy. The high rates of weight regain following treatment cessation further emphasise the need to manage obesity as a chronic disease.

Integrating bariatric care models into pharmacotherapy pathways may bridge current gaps and support more sustainable patient-centred outcomes.

Based on our arguments in this review, authors would like to suggest a checklist, presented in Table 1, for consideration by the healthcare professionals recommending these medications to their patients. Many of these recommendations need to be examined in adequately designed studies, but the framework can prove useful while those studies become widely available.

Table 1 Checklist for consideration by healthcare professionals before prescribing weight loss medications.

Pre-prescription checklist: Weight loss medications
Rule out eating disorders or major psychological issues
Education about healthy diet and muscle mass preservation exercise
Consideration regarding micronutrient deficiencies and supplementation
Counselling on alcohol use
Setting realistic patient expectations
Consideration regarding increased risk of gallstones