Summary
Introduction
Currently, trials are investigating the efficacy of nutrient‐stimulated hormone‐based therapies (NuSHs) in promoting weight loss in people living with overweight and obesity. However, the extent to which nutritional and functional outcomes are evaluated remains uncertain. Thus, we conducted a systematic mapping to assess the presence of nutritional and functional outcomes in randomized controlled trials (RCTs) investigating NuSHs.
Methods
We conducted a systematic mapping search on the Cochrane Central Register of Controlled Trials (CENTRAL), which includes ClinicalTrials.gov and the International Clinical Trials Registry Platform for interventional trials of NuSHs registered from inception to December 31, 2023. We excluded non‐ and quasi‐randomized trials, phase I trials, trials that did not include body weight as a primary or secondary outcome, trials with an intervention duration of less than 6 months, and trials that did not specify a body mass index threshold in their eligibility criteria. Outcomes included: dietary intake, eating behavior, body composition, physical performance, muscle strength, bone health, and levels of vitamins, trace elements, albumin, prealbumin, and hemoglobin.
Results
The search identified 2284 trials, of which 417 were included in the analysis. The proportion of RCTs that included nutritional assessment other than body weight increased over time. Approximately, 20.4% reported measurements of body composition, 17.3% reported measurements of albumin/prealbumin/hemoglobin, and 17% reported assessment of dietary intake and eating behavior. Evaluations of bone health, physical performance, muscle strength, and measurements of vitamins/trace elements were reported in less than 5% of the total trials each.
Conclusion
The present review has shown the sparse reporting of nutritional and functional outcomes in RCTs evaluating the impact of NuSHs.
Keywords: incretin therapy, nutrient‐stimulated hormone‐based therapies, obesity
1. INTRODUCTION
Obesity is a chronic disease and considered as a major driver of long‐term comorbidities and increased mortality. 1 , 2 Moreover, obesity frequently coincides with altered nutritional status, evidenced by nutrient deficiencies, loss of skeletal muscle mass and function, as well as increased frailty and disability. 3 , 4 Obesity management encompasses lifestyle modifications, pharmacotherapies, or bariatric surgeries, each offering varying degrees of success in weight loss. Recent advances, notably the integration of nutrient‐stimulated hormone‐based therapies (NuSHs), have marked a substantial improvement in obesity treatment and reduction of some comorbidities. 5 , 6 Randomized clinical trials (RCTs) have proved the efficacy of several new NuSHs in promoting weight loss in people living with overweight and obesity. NuSHs associated with a weight reduction of more than 10%, also known as double‐digit weight loss drugs, include high doses of glucagon‐like peptide 1 receptor (GLP‐1R) agonists and new‐generation double‐hormone agonists (GLP‐1/amylin and GLP‐1/glucose‐dependent insulinotropic polypeptide [GIP]), as well as triple‐hormone agonists (GLP‐1/GIP/glucagon agonists). 7 , 8 , 9
NuSHs induces weight loss through diverse biological actions, notably by reducing appetite and food intake. 10 , 11 The expected side effects, though moderate, can include nausea, vomiting, diarrhea, and constipation. 12 , 13 Due to substantial weight loss similar to the effects of bariatric surgery, 8 some NuSHs may influence the nutritional and functional status of people living with overweight and obesity, potentially placing them at risk of malnutrition. Several review articles highlight concerns about the excessive loss of lean mass and the risk of sarcopenia associated with reduced energy, micronutrients, and high‐quality protein intake, especially if adequate nutritional strategies are not implemented in patients receiving NuSHs. 14 , 15 , 16 Despite the rigorous scientific monitoring typically seen in RCTs of NuSHs, evidence regarding the evaluation of their impact on nutrition status in these trials seems scarce. This systematic mapping aimed to assess the existence of data collection regarding nutritional and functional assessment outcomes in trials investigating NuSHs registered in ClinicalTrials.gov and the International Clinical Trials Registry Platform (ICTRP).
2. MATERIALS & METHODS
The review protocol has been registered prospectively in the International Prospective Register of Systematic Reviews (registration number PROSPERO 2023: CRD42023480483) and was prepared according to the PRISMA statement.
2.1. Data sources and searches
The systematic mapping review was conducted to identify registered clinical trials related to NuSHs in the Cochrane Central Register of Controlled Trials (CENTRAL), which includes both the United States National Library of Medicine database of clinical trials, ClinicalTrials.gov and ICTRP. The list of drugs was initially sourced from the narrative review by Müller TD et al. 17 An updated list of NuSH drugs was elaborated through a search of PubMed and Embase databases. The list of search terms is provided in the supplementary materials (Table S1).
2.2. Study selection
The study selection process was guided by the PICOS framework (Population, Intervention, Comparison, Outcome, Study design), which was applied as follows: the population (P) included patients with overweight or obesity; the intervention (I) referred to NuSHs interventions as monotherapies or in combination; the comparison (C) involved comparisons between NuSHs interventions and other types of interventions (such as other drugs, lifestyle modifications, standard care, or bariatric surgery); the outcomes (O) focused on nutritional and functional outcomes; and the study design (S) included only RCTs. All RCTs registered in CENTRAL (including ClinicalTrials.gov and ICTRP) from inception to December 31, 2023 were selected. Trials were excluded if they met any of the following criteria: (1) non‐RCTs and quasi‐RCTs, (2) phase I RCTs, (3) withdrawn RCTs, (4) interventions with a duration of less than 6 months, (5) eligibility criteria not incorporating a body mass index (BMI) of 25 kg/m2 and more, (6) absence of weight or BMI as primary or secondary outcomes, (7) no clearly defined intervention duration, and (8) evaluation of non‐nutrient‐stimulated hormone‐based interventions. To remove duplicates, trials with multiple registered IDs (e.g., NCT numbers and EudraCT numbers) across databases were excluded. Additionally, sponsor protocol code numbers were cross‐checked among databases to ensure accurate identification and removal of all duplicates.
2.3. Data extraction
Upon identification of an RCT, the key trial characteristics were extracted (date of first submission, site, sponsor, setting, number of centers, primary outcome, condition, FDA‐regulated product, intervention, experimental, comparator, and intervention duration). In order to facilitate the data analysis, drugs were manually grouped into the following categories: GLP‐1 receptor agonists, GLP‐1/GIP dual receptor agonists, GLP‐1/glucagon dual receptor agonists, GIP receptor agonists, GIPR antagonist/GLP‐1 R agonists, glucagon analogs, GLP‐1/GIP/glucagon receptor tri‐agonists, GLP‐1R/GLP‐2R agonists, amylin analogs, GLP‐1/amylin dual receptor agonists, PYY analogs, or drugs targeting the ghrelin pathway.
The study's design and primary/secondary outcomes listed on ClinicalTrials.gov and ICTRP were reviewed to determine the presence or absence of planned nutritional and functional evaluation. Additionally, the online publication of trial protocols and results were examined to ascertain whether nutritional and functional evaluation was part of the study plan. To identify online publications, the publication link in ClinicalTrials.gov and ICTRP was utilized when posted. If no link was provided on the registry, systematic searches were conducted on PubMed, Embase, and Google Scholar using keywords for the drug, the principal investigator's last name, and the condition studied. For industry‐sponsored trials, the sponsor's website was also searched. If the publication was not identified, the principal investigator or the sponsor was contacted via email to inquire about nutritional and functional evaluations.
Evaluations included (1) assessment of dietary intake and eating behavior through dietary records, 24‐hour dietary recall, food frequency questionnaire, and eating behavior questionnaires, (2) analysis of body composition via bioelectrical impedance analysis, dual X‐ray absorptiometry, computed tomography scan or magnetic resonance imaging, (3) evaluation of physical performance and muscle strength (e.g. handgrip strength, walking distance), (4) assessment of bone health (bone mass, architecture, strength, and biomarkers), (5) measurement of vitamins and trace elements, and (6) measurement of albumin, prealbumin, and/or hemoglobin levels. The search and data extraction were performed by two independent investigators and disagreements were resolved by discussion.
2.4. Data synthesis and analysis
We quantitively summarized data based on study characteristics and nutritional and functional outcomes. Continuous variables were expressed as medians (interquartile range), while categorical variables were presented as numbers (percentages). To assess the association between trial characteristics and the reporting of nutritional and functional outcomes, we used Chi‐square and Fisher's exact tests. All Data were analyzed using R version 4.1.3.
3. RESULTS
Of the 3345 trial records obtained from ClinicalTrials.gov and ICTRP, 1061 were identified as duplicates. The remaining records underwent review for eligibility criteria and 417 trials were included in the review (Figure 1, Table S1). The primary reasons for exclusion were as follows: BMI not within eligibility criteria (n = 489), phase I trials (n = 434), intervention duration of less than 6 months (n = 393), and non‐randomized trials (n = 311). Records from published trials or protocols for 244 studies were reviewed. The remaining ones are either ongoing trials or their results have not been published. In the case of unpublished trials, efforts were made to gather additional information by contacting either the principal investigator or the sponsor, with a response rate of 4.6% from those contacted.
FIGURE 1.
PRISMA flow diagram for trial selection.
The description of selected phase II, III, and IV trials assessing the impact of NuSHs on weight, whether as a primary or secondary outcome is presented in Table 1. Most of the RCTs were sponsored by the industry (n = 276, 66.2%) and conducted across multiple centers (n = 294, 70.5%) and multiple countries (n = 200, 48.0%). Trials mainly included adults (n = 394, 94.5%), both men and women (n = 399, 95.7%), and individuals with a BMI of 30 kg/m2 or higher (n = 321, 77%). Individuals with a BMI of 25 kg/m2 or higher were included in 80.6% of the trials (n = 336). The median (interquartile range) follow‐up duration was 40 (26–52) weeks.
TABLE 1.
Characteristics of clinical trials investigating the impact of nutrient‐stimulated hormone‐based therapy on body weight as a primary or secondary outcome in individuals with overweight or obesity.
| Characteristics | No. (%) of trials |
|---|---|
| Status | |
| Completed | 258 (61.9) |
| Recruiting | 69 (16.5) |
| Not yet recruiting | 60 (14.4) |
| Unknown | 16 (3.8) |
| Terminated | 14 (3.4) |
| Sponsor | |
| Industry | 276 (66.2) |
| Non‐industry | 141 (33.8) |
| Number of centers | |
| Multicenter | 294 (70.5) |
| Single center | 103 (24.7) |
| No information | 20 (4.8) |
| Setting | |
| Multinational | 200 (48.0) |
| Single country | 217 (52.0) |
| FDA‐regulated Product | |
| Yes | 142 (34.1) |
| No | 62 (14.9) |
| Not provided | 213 (51.1) |
| Age eligibility | |
| ≥ 18 years | 394 (94.5) |
| < 18 years | 10 (2.4) |
| All ages | 13 (3.1) |
| Gender | |
| Males and females | 399 (95.7) |
| Females | 15 (3.6) |
| Not provided | 3 (0.7) |
| Main condition for eligibility | |
| Type 2 diabetes alone or associated with another condition | 217 (52.0) |
| Obesity alone or associated with another condition | 157 (37.6) |
| Type 1 diabetes alone or associated with another condition | 14 (3.4) |
| Other | 29 (7.0) |
| Overweight eligibility (BMI 25.0–29.9 kg/m2) | 336 (80.6) |
| Obesity class eligibility | |
| Class I (BMI < 35 kg/m2) | 28 (6.7) |
| Class I, II (BMI < 40 kg/m2) | 55 (13.2) |
| Class I, II, III (BMI ≥ 30 kg/m2) | 321 (77.0) |
| Class II, III (BMI ≥ 35 kg/m2) | 13 (3.1) |
| Primary endpoint | |
| Weight only | 97 (23.3) |
| Weight as coprimary endpoint* | 20 (4.8) |
| Treatment duration (weeks), median (interquartile range) | 40 (26–52) |
| GLP‐1 receptor agonists | |
| Liraglutide | 110 (26.4) |
| Semaglutide | 84 (20.1) |
| Exenatide | 71 (17.0) |
| Dulaglutide | 23 (5.5) |
| Lixisenatide | 21 (5.0) |
| Albiglutide | 14 (3.4) |
| Orforglipron | 10 (2.4) |
| Ecnoglutide | 4 (1.0) |
| Noiigliutide | 2 (0·5) |
| PB‐119 | 2 (0·5) |
| Danuglipron | 1 (0.2) |
| Lotiglipron | 1 (0.2) |
| GLP‐1/GIP dual receptor agonists | |
| Tirzepatide | 33 (7.9) |
| CT‐868 | 1 (0.2) |
| GLP‐1/Glucagon dual receptor agonists | |
| Survodutide | 5 (1.2) |
| Mazdutide | 3 (0.7) |
| Pemvidutide | 2 (0·5) |
| Oxyntomodulin | 1 (0.2) |
| Cotadutide | 1 (0.2) |
| Efinopegdutide | 1 (0.2) |
| Bamadutide | 1 (0.2) |
| JNJ‐64565111 | 1 (0.2) |
| GLP‐1/ GIP/Glucagon receptor tri‐agonists | |
| Retatrutide | 6 (1.4) |
| Efocipegtrutide | 1 (0.2) |
| GIPR antagonist/GLP‐1 receptor agonists | |
| AMG 133 | 1 (0.2) |
| Amylin analogs | |
| Cagrilintide | 1 (0.2) |
| Davalintide | 1 (0.2) |
| Pramlintide | 6 (1.4) |
| GLP‐1/Amylin dual receptor agonists | |
| CagriSema | 7 (1.7) |
| Drugs targeting the ghrelin pathway | |
| Livoletide | 1 (0.2) |
| PYY analogs | |
| PYY3–36 | 1 (0.2) |
Coprimary endpoints: adverse events, HbA1c, insulin resistance, Beta‐Cell Function, time in range glycemia, Kansas City Cardiomyopathy Questionnaire, WOMAC Pain Score, Apnea‐Hypopnea Index.
Approximately, 28% (n = 117) of the trials had weight assessed as either a primary or co‐primary outcome, while the remaining trials considered weight as a secondary outcome. Other primary outcomes included measures related to glucose metabolism, as well as cardiovascular, hepatic, and renal function and disease. The most investigated NuSHs were GLP‐1 receptor agonists (n = 343, 82.3%), with a predominant emphasis on liraglutide (n = 110, 26.4%), semaglutide (n = 84, 20.1%), and exenatide (n = 71, 17%). There has been a rising proportion of studies investigating the weight loss effects of NuSHs, other than GLP‐1 receptor agonists since 2017 (Figure 2). Notably, new types of drugs included GLP‐1/GIP dual receptor agonists, GLP‐1/glucagon dual receptor agonists, GLP‐1/amylin dual receptor agonists, and GLP‐1/GIP/glucagon receptor tri‐agonists.
FIGURE 2.
Temporal trend of RCTs by type of nutrient‐stimulated hormone‐based therapy and type of nutritional and functional outcomes.
Regarding nutritional outcomes, aside from weight, there has been a concurrent rise in the evaluation of nutritional assessments over time (Figure 2). A total of 252 studies (60.4%) did not report any nutritional outcomes. Body composition was reported in 20.4% of trials (n = 85) (Figure 3). DEXA was the primary method employed for measuring body composition, accounting for 53% of trials (n = 45/85). Other measurement techniques included bioelectrical impedance analysis (n = 10/85, 11.8%), computed tomography scan (n = 8/85, 9.4%), and magnetic resonance imaging (n = 14/85, 16.5%). Of the 417 trials, 17.3% (n = 72) reported measurement of albumin, prealbumin, and/or hemoglobin, and 17% (n = 71) reported assessment of dietary intake and/or eating behavior. Dietary intake was mainly estimated through food diaries and food frequency questionnaires. Evaluations of bone health, physical performance, muscle strength, and measurements of vitamins/trace elements were reported in less than 5% of the total trials each.
FIGURE 3.
Percentage of nutrient‐stimulated hormone‐based therapy clinical trials reporting nutritional and functional outcomes.
The proportion of trials reporting at least one nutritional or functional outcome was highest among industry‐sponsored trials (n = 89, 53.9%) (p < 0.001) and multicenter trials (n = 102, 61.8%) (p = 0.006) (Table 2). Additionally, trials that included both adults and older adults had a notably high reporting rate (n = 149, 90.3%) (p = 0.009). The percentage of nutritional and functional outcomes within each category of NuSHs is represented in the supplementary material (Figure S1).
TABLE 2.
Characteristics of trials reporting at least one nutritional or functional outcome.
| Characteristic and category | n (%) | p‐value |
|---|---|---|
| Sponsor | <0.001 | |
| Industrial | 89 (53.9) | |
| Non‐industrial | 76 (46.1) | |
| Setting | 0.219 | |
| Multinational | 73 (44.2) | |
| Single country | 92 (55.8) | |
| Number of centers | 0.006 | |
| Multiple | 102 (61.8) | |
| Single | 52 (31.5) | |
| Not available | 11 (6.7) | |
| Age | 0.009 | |
| ≥ 18 years | 149 (90.3) | |
| < 18 years | 7 (4.2) | |
| All ages | 9 (5.5) | |
| Gender | 1.000 | |
| Males and females | 158 (95.8) | |
| Females | 6 (3.6) | |
| Not provided | 1 (0.6) | |
| Drug | 0.636 | |
| GLP‐1 receptor agonists | 133 (80.6) | |
| GLP‐1/GIP dual receptor agonists | 15 (9.1) | |
| GLP‐1/Glucagon dual receptor agonists | 5 (3.0) | |
| Amylin analogs | 5 (3.0) | |
| GLP‐1/Amylin dual receptor agonists | 3 (1.8) | |
| GLP‐1/ GIP/Glucagon receptor tri‐agonists | 2 (1.2) | |
| GIPR antagonist/GLP‐1 receptor agonists | 1 (0.6) | |
| Drugs targeting the ghrelin pathway | 1 (0.6) | |
| PYY analogs | 0 (0) |
4. DISCUSSION
Our systematic mapping has shown for the first time the sparse reporting of nutritional and functional outcomes in RCTs of NuSHs. However, it is necessary to recognize that NuSHs, particularly GLP‐1 receptor agonists, were initially developed for glycemic regulation in type 2 diabetes due to their incretin effect. Recent evidence has shown their remarkable efficacy in inducing weight loss in people living with obesity, irrespective of diabetes status. 18 Interestingly, our findings indicate a growing emphasis on expanding the understanding of how NuSHs influence nutritional and functional status over time, demonstrating the recognition of these previously overlooked areas of importance.
Research into the next generation of NuSH pharmacotherapy for obesity is on the horizon. Given that the biological impacts and potential adverse events of these drugs can lead to shifts in nutritional and functional status especially if administered for a long term, understanding these alterations in people living with obesity becomes pivotal for advancing precision management of obesity and personalized nutritional care. 19 , 20
Approximately, 17% of registered trials documented dietary intake assessments and measurements of albumin, prealbumin, and hemoglobin, with fewer than 5% monitoring levels of vitamins and trace elements in blood serum. The administration of NuSHs frequently results in reduced food intake and several gastrointestinal side effects, potentially contributing to nutritional deficiencies. 13 Evaluating patients' dietary habits and measuring their vitamin and mineral levels is crucial to prevent deficiencies and enhance treatment safety in the long term since obesity is a chronic disease probably needing lifelong suspensive drugs.
Furthermore, given the important consequences of NuSHs on body weight, it is necessary to pay specific attention to the evaluation of body composition. Alongside the significant reduction in fat mass, individuals living with overweight and obesity receiving NuSHs may experience a reduction in lean mass, mainly through skeletal muscle loss. 8 , 21 Importantly, the loss of skeletal muscle frequently accompanies a well‐recognized syndrome known as sarcopenic obesity. It is characterized by the simultaneous decline in both skeletal muscle mass and muscle strength, which correlates with diminished physical capabilities and impaired functional mobility. 22 Surprisingly, only 20% of registered trials have incorporated assessments of body composition, including lean or skeletal muscle mass, with fewer than 5% including evaluations of physical performance. While initiatives aimed at preserving lean mass, such as integrating physical activity into treatment regimens, are already planned in RCTs, 6 it is crucial to underscore the importance of measuring body composition and identifying sarcopenia to ensure that NuSHs does not exacerbate weight‐loss‐induced sarcopenia.
Another crucial aspect of body composition deserving attention is bone tissue. The current review uncovered a paucity of data regarding bone health assessment. Significant weight loss often leads to a reduction in bone mass, increasing the risk of fractures, particularly among peri/post‐menopausal women, the elderly, and in patients who are often vitamin D deficient. While only a few studies have investigated the impact of NuSHs on bone health, some, such as low‐dose GLP‐1 receptor agonists, have shown potential in preventing bone loss and fractures, suggesting a positive influence on bone health. 23 Nonetheless, the existing evidence remains insufficient and it is imperative to conduct comprehensive evaluations in all high‐risk groups to better elucidate the effects of NuSHs on bone health. 24
The current systematic mapping offers an up‐to‐date overview of nutritional and functional evaluation within completed and ongoing RCTs of NuSHs. Identifying the gap in such assessments should raise awareness among investigators and sponsors about the significance of integrating nutritional and functional evaluation beyond body weight in future RCTs. This integration is crucial for minimizing the risk of inaccurate measures of efficacy when evaluating novel anti‐obesity medications. 25 It is essential to encourage the involvement of nutrition experts in research teams and address methodological considerations related to the measurement, analysis, and reporting of nutritional and functional outcomes in RCTs of NuSHs. Particular attention should be given to non‐industrial and monocentric trials. Ensuring the collection of high‐quality data will facilitate future meta‐analyses and help establish evidence‐based recommendations.
Some limitations should be considered when interpreting the findings. (1) Assessment of nutritional and functional outcomes relied on information reported in the ClinicalTrials.gov and ICTRP registry, any available published trials and protocols, and responses from investigators and sponsors contacted by email, acknowledging that not all responded to our inquiries. Consequently, our data may not precisely reflect the nutritional assessment originally planned in RCTs. (2) Many trials were excluded from the present review due to the absence of BMI among the eligibility criteria, but in some cases, there are further inclusion and exclusion criteria that are not well reported in the ClinicalTrials.gov and ICTRP registry.
5. CONCLUSION
The low prevalence of nutritional and functional assessments in clinical trials of NuSHs leaves a significant evidence gap regarding the consequences of these drugs. As several novel NuSHs are currently under development, future research should broaden its focus beyond weight management alone to address all aspects of the patient's nutritional status, particularly in children, the elderly, and individuals at high risk of malnutrition, such as post‐bariatric surgery subjects. This includes addressing potential nutrient deficiencies, monitoring nutritional biomarkers, assessing body composition (including lean and bone mass), and evaluating physical performance and muscle strength to ensure safe and efficacious pharmacotherapy for individuals living with overweight or obesity.
AUTHOR CONTRIBUTIONS
NR performed the search and was the first reviewer for article screening, and for data extraction and quality appraisal. NS, CC, and CRL were the second reviewers for article screening, and for some data extraction and quality appraisal. NR was responsible for the data that was used to perform the statistical analysis. SC and NR wrote the first draft of the manuscript with input from CC, FH, and CRL. All authors reviewed the manuscript and provided input on the writing of the manuscript.
DECLARATION OF INTERESTS
Nathalie Rassy, Frank B. Hu: none reported. Nicholas Shoung: Personal fees from Eli Lilly outside the submitted work.
Sébastien Czernichow: Personal fees from Bariatek, NovoNordisk, Eli Lilly, Pfizer, Fresenius Kabi, Ipsen Pharma, Janssen‐Cilag, Boehringer Ingelheim, and Novartis outside the submitted work. He holds shares of ALIFERT, JELLYNOV.
Claire Carette: Personal fees from Boehringer Ingelheim, Axis Santé, Pfizer, Bioprojet Pharma, Novo Nordisk, Astra Zeneca, Novartis, Ipsen, MSD, Eli Lilly and Publicis Health and nonfinancial support from Rhythm, Novo Nordisk, MSD, Novartis, Eli Lilly, Sanofi, Astra Zeneca, Bristol‐Myers Squibb, Abbott, Amgen, Vifor and Fresenius Kabi outside the submitted work.
Claire Rives‐Lange: Personal fees from Nestlé Health Science outside the submitted work. Supports for attending meetings: Nestlé home care and Fitform outside the submitted work.
Supporting information
Table S1: List of nutrient‐stimulated hormone‐based therapeutics and search terms.
Table S2: Registered ID of included trials.
Figure S1. Percentage of nutritional and functional outcomes within each category of nutrient‐stimulated hormone‐based therapy.
ACKNOWLEDGMENTS
There was no funding source for this study. We thank all the authors of the included trials that provided us with additional unpublished data from their studies.
Czernichow S, Rassy N, Carette C, Shoung N, Hu FB, Rives‐Lange C. Nutritional and functional outcomes in trials of nutrient‐stimulated hormone‐based therapy—A systematic mapping review. Obesity Reviews. 2025;26(5):e13890. doi: 10.1111/obr.13890
Sébastien Czernichow and Nathalie Rassy equally contributed to the paper.
Funding information This research did not receive any specific grant from funding agencies in the public commercial or not‐for‐profit sectors.
DATA AVAILABILITY STATEMENT
Data extracted from trials and used in our analysis will be made available upon request via email to the corresponding author on the provision of an analytical plan. Data provided to us directly by investigators of the included trials will not be shared unless the investigators requesting data obtain permission from the original study authors.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Table S1: List of nutrient‐stimulated hormone‐based therapeutics and search terms.
Table S2: Registered ID of included trials.
Figure S1. Percentage of nutritional and functional outcomes within each category of nutrient‐stimulated hormone‐based therapy.
Data Availability Statement
Data extracted from trials and used in our analysis will be made available upon request via email to the corresponding author on the provision of an analytical plan. Data provided to us directly by investigators of the included trials will not be shared unless the investigators requesting data obtain permission from the original study authors.