Macronutrient, Micronutrient Supplementation and Monitoring for Patients on GLP-1 Agonists: Can We Learn from Metabolic and Bariatric Surgery?

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have become central to the management of obesity, especially in the current climate with increasing rates of adiposity-related morbidity and mortality globally, supported by a strong evidence base from large cardiovascular outcome trials. Early trials have clearly demonstrated not only safety but also meaningful efficacy, with liraglutide in the LEADER trial achieving significant reductions in cardiovascular risk [1], such as a multicentre, double-blind outcomes study enrolling 9340 adults with type 2 diabetes and high cardiovascular risk, followed for 3.8 years. Semaglutide in SUSTAIN-6 produced sustained glycaemic and weight benefits [2], as shown in a 2-year, randomised, placebo-controlled trial of 3297 participants with type 2 diabetes at elevated cardiovascular risk. Dulaglutide in REWIND confirmed long-term cardiometabolic improvements [3] based on a 5.4-year outcomes trial including 9901 adults, many without established cardiovascular disease. More recently, semaglutide in the STEP-1 trial produced mean weight losses of approximately 15% in individuals living with obesity [4] in a 68-week randomised trial of 1961 adults with overweight or obesity. The dual GIP/GLP-1 agonist tirzepatide in SURMOUNT-1 achieved reductions exceeding 20% in some participants [5], as demonstrated in a 72-week, phase 3 trial enrolling 2539 adults with obesity. These drugs have paved the way for the efficient invention of even more efficacious drugs in the future. The development of successful pharmacotherapy for obesity and its associated diseases is one of the greatest medical achievements of our age. Many of these drugs attempt to mimic the physiological effects of Metabolic and Bariatric Surgery (MBS). It is, therefore, natural that we try to understand if there is more that we can learn from MBS when using pharmacotherapy for obesity and metabolic syndrome. In this review, we seek to explore the nutritional consequences of pharmacotherapy for obesity and attempt to draw lessons from our experience with MBS.

Appetite suppression, gastrointestinal side effects, and reduced dietary variety seen with GLP-1 RAs can substantially lower energy intake, sometimes to levels insufficient to meet daily requirements for key micronutrients such as iron, calcium, zinc, and vitamins A, D, E, K, B1, B12, and C [6]. These risks are amplified in individuals with obesity, who frequently present with suboptimal baseline diets and pre-existing deficiencies, alongside obesity-related alterations in nutrient absorption and metabolism [7].

Despite these vulnerabilities, there are currently no consensus guidelines for micronutrient monitoring in patients receiving GLP-1 RAs. This contrasts sharply with MBS, where societies such as the British Obesity and Metabolic Society (BOMSS) [8], the American Society for Metabolic and Bariatric Surgery) [9], the European Society for Clinical Nutrition and Metabolism (ESPEN) [10], and the European Association for Endoscopic Surgery (EAES) [11] provide detailed protocols for baseline screening, ongoing laboratory monitoring, and prophylactic micronutrient supplementation. The lack of guidance in pharmacological obesity care, therefore, highlights a critical gap and provides the rationale for exploring whether lessons from bariatric surgery can inform clinical practice in GLP-1 RAs users.

Although pharmacological and surgical approaches differ fundamentally, both GLP-1 receptor agonists and MBS induce weight loss through reductions in appetite, altered nutrient handling, and changes in gastrointestinal physiology [12]. GLP-1 RAs act pharmacologically to slow gastric emptying, suppress appetite, and reduce overall caloric intake, often accompanied by gastrointestinal side effects such as nausea, vomiting, or diarrhoea, which can further limit the variety of food intake in patients [13]. Most of these effects are similar to what is observed after MBS—the only difference being that the bypass of parts of the gastrointestinal tract in some procedures, such as gastric bypasses, can further exacerbate these nutritional issues in particular cases of MBS by affecting the absorption of nutrients [14].

Despite these differences, there is significant overlap in nutritional consequences. Both interventions increase the risk of nutritional deficiencies due to reduced intake, altered absorption, or changes in gastrointestinal physiology [15]. Importantly, while MBS has long been recognised as necessitating structured micronutrient monitoring and supplementation, similar protocols for GLP-1 therapy have not yet been established. Hence, we explore the value of drawing on MBS guidelines to inform the nutritional management of patients on GLP-1 RAs.

Across the included studies, the type and validity of methods used to characterise nutrient intake and deficiency varied substantially. Dietary intake studies most commonly relied on self-reported 24 h recalls, short food diaries, or appetite questionnaires (e.g., in Christensen et al. [16] and Johnson et al. [17]), all of which are vulnerable to under-reporting in individuals with overweight or obesity. In contrast, higher-quality trials such as Silver et al. [18] and Richardson et al. [19] used weighed 3–7-day food diaries with dietitian-verified nutrient analysis, providing a more reliable measure of energy and protein intake. Biochemical definitions of deficiency were used only in retrospective cohorts such as Butsch et al. [20], where serum B12, ferritin, thiamine, vitamin D, and anaemia levels were extracted from electronic health records. These methodological differences are important when interpreting results, as studies relying solely on reported intake may underestimate true nutrient insufficiency.

GLP-1RA therapy consistently reduces overall energy intake [16,21,22,23,24], in line with its well-documented anorexigenic effects [25]. Christensen et al. reported a 16–39% reduction in total caloric intake among GLP-1RA-treated cohorts [16], drawing on a narrative synthesis of multiple small dietary-intake studies involving adults with overweight or obesity. Although descriptive in nature, this review pooled findings from trials using validated 24 h dietary recalls and appetite questionnaires, providing an overarching estimate of caloric reduction across different GLP-1RA drugs. A recent systematic review described cases of severe caloric restriction (<800 kcal/day), frequently accompanied by suboptimal intake of macro- and micronutrients, representing a clinically significant risk [22]. Despite these reductions, energy intake often remains above recommended thresholds [23,24]. Similarly, Silver et al.(2023) demonstrated a 30% reduction in total energy intake with liraglutide compared with caloric restriction alone, confirming that pharmacological appetite suppression exerts additional effects on satiety [18]. Unlike Christensen et al., Silver et al. conducted a rigorously controlled 14-week randomised trial (n = 113) in adults with obesity and prediabetes, using 3-day weighed food diaries analysed by trained dietitians. This methodology provides a more precise estimate of nutrient intake and enables clearer observed reductions to liraglutide rather than other possible behavioural confounders.

Protein intake shows heterogeneous trends. Some studies demonstrate a higher proportion of caloric intake from protein following GLP-1RA initiation [18], whereas others report no significant difference [23,24]. Cross-sectional data indicate, however, that most patients fail to achieve protein intake levels required to preserve lean body mass (1.2–2.0 mg/kg/day) [17]. In a subset of patients, Butsch et al. reported sarcopenia associated with GLP-1RA initiation, potentially linked to inadequate protein intake [20]. This retrospective cohort study analysed electronic health records from adults with type 2 diabetes prescribed GLP-1RAs (n > 4000), incorporating objective biochemical markers, ICD-10 coding, and body-composition-linked surrogate measures. Unlike the intake-based methodologies of Christensen et al. and Silver et al., Butsch et al. used laboratory-verified nutritional deficiencies and clinically coded muscle-loss phenotypes, thereby providing biochemical and functional evidence of protein inadequacy rather than self-reported dietary data.

Delayed gastric emptying, appetite suppression, and altered gut microbiota induced by GLP-1RAs may influence micronutrient absorption. A large retrospective study of 461,328 adults initiating GLP-1RA therapy found that over 22% developed at least one nutritional deficiency within 12 months, most commonly vitamin D (13.6% at 12 months), followed by thiamine, other B vitamins, and anaemia [20].

Dietary intake studies corroborate these findings, showing that GLP-1RA users frequently fail to meet Recommended Dietary Intakes for vitamins A, C, D, E, and K, as well as dietary fibre [17,19]. Obesity itself is associated with deficiencies in vitamins A, D3, E, B12, thiamine, folate, and other B vitamins [7,26]. The combined effect of obesity and GLP-1RA therapy, therefore, represents a clinically significant risk. This is particularly relevant for patients concurrently receiving metformin, which may potentiate vitamin B12 deficiency [27].

GLP-1RA therapy has also been implicated in mineral deficiencies. Individuals with obesity often have inadequate intake of essential minerals such as iron, calcium, magnesium, zinc, and copper, increasing their vulnerability during GLP-1RA treatment [7]. Johnson et al. demonstrated that dietary intake of calcium, magnesium, potassium, and iron frequently fell below Dietary Reference Intakes (DRIs), while copper, phosphorus, selenium, and zinc were generally sufficient, and sodium was consumed in excess [17]. Similarly, it has been reported that average reductions of 14% in magnesium and 10% in iron intake following liraglutide treatment compared with dietary restriction alone [17].

In contrast, a randomised controlled trial found iron intake to be sufficient but identified persistent inadequacy in potassium intake across a large proportion of participants [19]. A study of long-term weight loss maintainers achieved through dietary intervention, rather than pharmacotherapy, reported higher adherence to mineral requirements compared with weight-stable individuals living with obesity [28]. These findings do, however, seem counterintuitive, and generally, we expect patients on GLP-1 RAs to experience nutrient deficiencies similar to MBS if additional supplements are not recommended. Though the overall effect may be less severe than some MBS procedures (gastric bypasses, for example), the cumulative effect of these deficiencies over time is likely to lead to serious nutritional issues.

MBS is a well-established risk factor for macro and micronutrient deficiencies [29]. Accordingly, both UK and international guidelines recommend structured, lifelong monitoring of micronutrient status in patients undergoing these procedures. The American Society for Metabolic and Bariatric Surgery (ASMBS) similarly endorses pre-operative nutritional assessment and post-operative screening of iron, B12, folate, and vitamin D, with broader testing considered for patients undergoing hypoabsorptive procedures [8]. The British Obesity and Metabolic Specialist Society (BOMSS) advises comprehensive pre-operative nutritional assessment by a trained dietitian, including biochemical evaluation of ferritin, folate, vitamin B12, 25-hydroxyvitamin D, and calcium, with correction of any deficiencies before surgery [8].

Post-operative protocols outlined by BOMSS recommend regular monitoring of these micronutrients after MBS with additional evaluation of zinc, copper, and vitamin A, depending on the surgical procedure [30]. Both BOMSS and ASMBS recommend annual monitoring of vitamin B12 and vitamin D, alongside routine multivitamin supplementation containing iron, selenium, zinc, copper, and thiamine for all patients [8,30]. The European Association for Endoscopic Surgery and the Enhanced Recovery After Surgery Society also support routine nutritional surveillance, although without detailed protocols [31,32]. A summary of key bariatric surgery guidelines outlining recommended micronutrient monitoring and supplementation schedules is presented in Table 1:

Both GLP-1 receptor agonist therapy and MBS achieve substantial and sustained weight loss through appetite regulation and gastrointestinal modification; however, their nutritional consequences differ somewhat in both aetiology and magnitude. MBS, particularly diversionary procedures such as One Anastomosis Gastric Bypass or Roux-en-Y Gastric Bypass, are consistently associated with deficiencies in iron, vitamin B12, folate, calcium, and fat-soluble vitamins due to altered intake and absorption [33,34,35]. Reduced protein intake is also well documented [36,37,38] and, if uncorrected, may contribute to undesirable reductions in fat-free mass [36]. In both bariatric surgery and GLP-1RA contexts, changes in body composition reflect alterations in fat mass (FM) and skeletal muscle mass (SM), the two principal components of weight loss. Distinguishing between FM loss and SM loss is clinically relevant, as disproportionate reductions in SM are associated with sarcopenia and adverse metabolic outcomes. However, most GLP-1RA studies do not report FM and SM separately, limiting the ability to assess muscle preservation or identify subgroups at higher nutritional risk for further analysis. In contrast, the nutritional effects of GLP-1RAs are primarily due to reduced intake. Consequently, their nutritional risks cannot be assumed to mirror those following MBS.

While nutritional complications after MBS are well characterised, with comprehensive, evidence-based monitoring and supplementation protocols firmly established [8,30,31,32,39], comparable frameworks for GLP-1RA therapy do not exist. The Obesity Society and others have outlined broad nutritional priorities for patients undergoing obesity management [40], emphasising dietary counselling and surveillance; however, these recommendations lack the specificity of post-bariatric guidelines. The recent joint advisory highlights these themes by outlining practical nutritional and lifestyle priorities for patients initiating GLP-1RA therapy, including baseline assessment of dietary habits, muscle strength, body composition, and social determinants of health, as well as strategies to manage gastrointestinal side effects, preserve muscle and bone mass, and prevent micronutrient deficiencies [40]. However, these recommendations lack the structured biochemical surveillance found in established bariatric surgery pathways. Therefore, the conclusions of our review hope to extend this advisory by identifying specific nutrient vulnerabilities reported in GLP-1RA studies and by highlighting the value of adapting elements of post-bariatric monitoring frameworks to pharmacological obesity care.

More recently, it has been emphasised that GLP-1 therapy poses unique nutritional challenges, such as reduced food volume, altered feeding behaviour, and micronutrient dilution effects, and the review had called for integrated dietary intervention and biomarker monitoring protocols [41].

Given the increasing global use of GLP-1RAs and the limited duration and scope of existing studies, rigorous longitudinal research is warranted to delineate their nutritional consequences and to inform structured, evidence-based monitoring and supplementation strategies [16,40].