It is important to continuously monitor and assess the long-term treatment efficacy and safety and the benefit-harm balance. Without systematic and quantitative assessments, the balance of benefit in terms of weight reduction against the potential harms would be unclear. We searched PubMed as of April 10, 2024, for any benefit-harm (risk) assessments (and related studies) on GLP-1 RAs. The net benefit was found to be highly dependent on patient preferences, i.e., the individual’s willingness to accept harms (or their risk aversion) to achieve weight reduction. Tirzepatide exhibited less favourable overall benefit compared to semaglutide and liraglutide as some harm outcomes were observed more frequently in the tirzepatide therapy, such as hypoglycemia, injection site reactions, and alopecia. For instance, semaglutide, liraglutide, and tirzepatide met the 0.6 probability threshold for net benefit at preference weights of 0.20, 0.19, and 0.28 for achieving a 5% weight loss and at preference weights of 0.14, 0.22, and 0.24 for achieving a 10% weight loss (Fig. 2a). Strength Exercises After 50 You Can Do Daily The effects were qualitatively consistent across the specific GLP-1 RA analogues.Therefore, this review focuses on semaglutide and liraglutide and aims to explore current discoveries of their effect on ingestive behavior.As a result, Adequate Intake (AI) volumes for water (i.e., which are not daily water requirements) were developed from median TWI values in the NHANES III survey database .The GLP-1 RAs were considered to be net beneficial when the probability of net health benefit reached at least 0.60.In contrast to the methods used in the NAM and EFSA reports, we propose that minimal/baseline fluid-electrolyte regulatory responses by the brain signal body water balance (i.e., euhydration), and that increased neuroendocrine responses (e.g., plasma AVP levels) represent the threshold at which the brain begins to defend body water volume and concentration (i.e., hypohydration).Using similar methods, a trial including 15 patients with type 2 diabetes mellitus (T2D) treated with oral semaglutide conducted by Gibbons et al. verbally reported a decreased preference for both high-fat and sweet foods from the snack box .Finally, Kadouh et al. used a 100 mm VAS to measure preference for fatty, salty, sweet, and savory foods .Altered food preferences, decreased food cravings, and reduced food intake may contribute to long-term weight loss. Although not shown in the plots, cholecystitis also had no impact on the benefit harm balance for similar reasons. Weight loss was the most influential outcome on the net benefit of GLP-1 RAs, followed by side effects like nausea, diarrhoea, constipation, and vomiting, which were relatively frequent. Probability that the absolute net benefit exceeds zero or that the benefit outweighed the harms. GLP-1 RAs modulate appetite regulation, which includes slowing gastric emptying, increasing satiety, and reducing appetite, resulting in weight loss.9,10 The benefits of weight reduction are consistent across RCTs, with great potential to address the obesity pandemic. The findings showed that the 10% weight loss outweighed the harms over 2 years of treatment with GLP-1 RAs, but the 5% weight loss did not. The current study evaluated the benefit-harm balance, factoring in all negative and positive outcomes on the same scale. The systematic reviews showed that GLP-1 RAs effectively reduce weight in people living with obesity (but without diabetes), particularly in the initial years of treatment. This property makes PRT beneficial for studying changes in appetitive responsiveness in patients . The method was built on previous studies that used PRTs in humans 27,28,29,30,31,32,33. This suggests an element of reward and reinforcement driving appetitive behavior . Satiety (resulting in a delay of the onset of the next meal) often continues even after the plasma levels have started to return to baseline. Satiation (resulting in a meal being stopped) occurs much sooner than the peak of the plasma levels. The expanding use of GLP1RAs for chronic weight management and the exploration of their broader cardiometabolic impacts highlight their growing significance and expansive potential in modern therapeutic strategies. Although GI adverse effects are commonly reported, their overall safety profile remains strong, and concerns about severe adverse effects such as gastroparesis and pancreatitis have not been substantiated in findings from prospective trials. GLP1RAs have significantly advanced the management of T2DM, kidney health, and CV health, supported by robust findings from CVOTs. Effects are dependent on agent potency and dose, and typically include various upper GI (nausea, vomiting) and lower GI (diarrhea, constipation) symptoms.2,3 Notably, participants receiving placebo in these trials often also report significant rates of these symptoms, and between-group differences in cessation due to intolerable adverse effects remain low.3 In addition to slower dose uptitration, various toolkits have been developed to assist in tolerability, as highlighted and summarized in the text and figures of a recent review.10 The snack boxes were weighed before and after consumption to determine the composition of the food consumed by the participants. Most of the human studies done to date relied on verbal reports and used a 100 mm visual analog scale (VAS) to assess satiety and fullness 43, 45,46,47, 54. This allows for almost continuous monitoring of ingestive behavior, tracking changes in consumption speed throughout the meal, and provides much more information than simply weighing the meal before and after eating occurs . From its initial development by Kissilef et al. in 1980, the Universal Eating Monitor (UEM) provided the novel ability to test rates of consumption for solid and liquid foods, thereby considering consistency as a satiating influence 7, 67. A deeper understanding of this and other consequences of chronic dosing schedules of GLP-1R agonizts will provide a more complete understanding of the long-term limitations and benefits of the medication, especially as it pertains to humans. Of course, once you digest these foods, you’ll eventually become hungry again. Given the excitement surrounding them, social media is full of food concoctions and supplements touted as “natural GLP-1s” or “nature’s Ozempic.” It stimulates the release of insulin, another hormone whose job it is to take glucose from the bloodstream and push it into the body’s cells where it can be used for energy. While these drugs have helped millions of individuals reach their weight loss goals, many suffer side effects that ultimately lead them to discontinue use, resulting not only in money lost, but weight regain. That leads to weight loss, says Supriya Rao, MD, a doctor in internal medicine, gastroenterology, obesity medicine, and lifestyle medicine in Boston. It is high in calories, which can slow weight loss progress, and it may worsen side effects like nausea or diarrhea. The right meal plan can help you maintain energy, stay on track with your weight and health goals, and minimize potential side effects. Added value of this study Ingestive behavior using direct and objective measures not contingent on verbal reporting has not yet been reported for patients in the weight-loss maintenance phase, which raises the question whether the patients may return to baseline (pre-intervention) food choices. While in the weight loss phase, patients had decreased preference for high-fat, non-sweet foods as directly measured by consumption of an evening ad libitum snack box . The STEP 5 study evaluated semaglutide over 2 years which captured both the initial weight loss and weight-loss maintenance phases . Semaglutide resulted in reduction of body weight of up to 15% over 12–18 months in adults and adolescents with obesity . By binding to GLP-1R in the subcortical areas of the brain, semaglutide has been suggested to potentially affect taste preferences and food intake behaviors via interaction with proopiomelanocortin neurons and cocaine- and amphetamine-regulated transcripts . If these findings are supported by future controlled intervention studies, it is possible that increased daily water consumption will be recognized as a safe, cost-effective, simple primary preventive intervention for some kidney diseases 117,131. Third, because of the large number of confounding dietary, behavioral, and genetic factors related to the development of the above diseases, the number of subjects required for adequately-powered statistical analyses which isolate the effects of water is large and the research is costly. A 6-week study, involving 82 healthy adults (50% ♀) in three TWI groups (1.43, 1.83, and 2.42 L/24h), provided promising evidence (i.e., increasing the daily TWI of the two LOW groups to match 2.42 L/24h) of reduced circulating copeptin levels . This suggests that women who consume a TWI of 0.7–1.6 L/24h (i.e., ~20–30% of young healthy women; Figure 2)—well below the AI recommended by EFSA and NAM (Table 1)—experience a chronic mild-to-moderate neuroendocrine defense of total body water. Recent developments have introduced GLP-1 analogs as a highly viable option for the treatment of obesity, representing the newest generation of therapeutic models for weight management. The study showed a decreased preference for both high-fat and sweet foods after treatment with GLP-1 analog . In this study, energy density was measured as the amount of energy or calories in a particular weight of food (kcal/g). Ingestive behavior using verbal reports has not yet been reported for patients in the weight-loss maintenance phase, which raises the question again whether the patients may return to baseline (pre-intervention) food choices. Five previous studies used verbal reports to show decreased intensity of food cravings as well as a change in the types of foods they crave after GLP-1 analog treatment 43, 45, 47, 48, 54. As a result, Adequate Intake (AI) volumes for water (i.e., which are not daily water requirements) were developed from median TWI values in the NHANES III survey database . Thus, an individual with suboptimal water intake may be evaluated to be euhydrated due to the defense of POSM through reduced urine production and other compensatory responses. The present review analyzes published evidence that is relevant to these issues and presents a novel approach to assessing the daily water requirements of individuals in all sex and life-stage groups, as an alternative to AI values based on survey data. If you experience these symptoms, increase your water intake gradually and seek medical attention if symptoms persist. The interface adapts to your screen size, making it easy to calculate your daily water needs on the go. We have analyzed the relationship between 24-h TWI values and their corresponding plasma AVP levels from multiple research studies, and identified a plasma AVP concentration that approximates the neuroendocrine response threshold for water regulation in free-living adults. In contrast to the methods used in the NAM and EFSA reports, we propose that minimal/baseline fluid-electrolyte regulatory responses by the brain signal body water balance (i.e., euhydration), and that increased neuroendocrine responses (e.g., plasma AVP levels) represent the threshold at which the brain begins to defend body water volume and concentration (i.e., hypohydration). National Academy of Medicine (NAM) publication, which presented dietary reference intakes for water , included a lengthy review of water balance studies and water needs (i.e., using the stable isotope of water D2O) of children and adults (Table 1). This empirical method focuses on the intensity of a specific neuroendocrine response (e.g., plasma arginine vasopressin (AVP) concentration) employed by the brain to regulate total body water volume and concentration. Due to the prevalence of post-operative weight regain, anti-obesity medications are often prescribed to supplement the effects of bariatric surgery . Direct observation of ingestive behaviors may also introduce social desirability bias by unintentionally causing participants to alter their normal activity in a conscious or subconscious effort to align with social norms regarding food intake . Measuring food-intake directly, without relying on verbal reports, is an objective means of collecting ingestive behavior data, but there are practical challenges. These behaviors can be studied in both humans and animals and can yield important insights that assist clinicians in managing patient expectations when using anti-obesity treatments. Of note, although tirzepatide is additionally a glucose-dependent insulinotropic polypeptide (GIP) RA,20 in this study we refer to all treatments as GLP-1 RAs for better readability. We performed a benefit-harm balance modelling, which will be updated as new evidence emerges. However, as evidence on the topic is accumulating rapidly, there is a need for continuous evaluation and monitoring of the benefit-harm balance to guide up-to-date decisions. The net benefit was sensitive to patient preferences, implying that the treatment should be personalized to individuals, taking into account patient treatment goals, outcome risks, and preferences. Although it is beyond the scope of this study, a companion project within the LOOBesity cohort at the University of Zurich and University Hospital of Zurich is developing a benefit–benefit decision aid aimed at personalized treatments for individual patients.46 The between-individual variation of net benefit could also be much higher than that shown in this study if we simultaneously consider individual preferences for all outcomes. For example, one of the harm outcomes that highly influenced the unfavourable benefit-harm balance of tirzepatide was alopecia. Even the 5% weight loss could be net beneficial for individuals who place greater preference on the weight reduction and less concern on the potential harms. Add soluble fiber-rich foods, such as beans, lentils, berries, and oats, to your diet to support weight loss and nutrient intake. Another weight loss benefit is GLP-1’s effect on the brain’s reward system, where it can reduce cravings by quieting the running thoughts about food. As many employers already know, adding obesity management programs to health benefit plans can boost employee motivation and health outcomes. This first quantitative benefit-harm balance analysis showed that GLP-1 RAs derive a net benefit for achieving a weight reduction of at least 10% from baseline over the first and second years of treatment. Neuroendocrine Responses across a Range of TWIs During the weight loss phase of semaglutide treatment, energy intake substantially decreased 43,44,45,46,47. When assessing consummatory behavior, it is important to consider the types of food that patients who undergo anti-obesity treatment choose to consume. Whilst in humans, gastric bypass results in weight loss, reduced food intake, and reduction in rate of eating, but no change in food selection or frequency of eating . Gastric bypass in rodents results in weight loss, reduced food-intake, reduction in preference for sucrose and intralipid during a two-bottle preference test, reduced consumption of fat, with a modest increase in protein intake 11, 12. The magnitude of the effect on weight loss of 5% was also in a similar order. Semaglutide showed a relatively larger effect (RR 5.42, 4.53–6.50), followed by tirzepatide (4.29, 3.65–5.05) and liraglutide (2.91, 2.19–3.87) in achieving the 10% weight loss target. The number of individuals achieving a weight loss target of ≥5% and ≥10% from baseline was significantly higher in the GLP-1 RA group than placebo, with a relative risk (RR) of 2.51 (95% CI 2.37–2.66) and 4.11 (3.45–4.90), respectively. The summary treatment effects of GLP-1 RAs are shown in Table 2 (see detailed results in AppendixSupplementary Fig. S2). Create a file for external citation management software An estimated 5 million Americans are now incorporating these drugs into their weight-loss strategies, underscoring their transformative impact and accessibility. Weight loss often tops the list of resolutions, and with the emergence of GLP-1-based medications, reaching your ideal weight has become more attainable than ever. The New Year is here, and for many of us, it’s the perfect time to reflect, reset, and commit to achieving our health and fitness goals. Firstly, guided by insights from some of the RCTs,34, 35, 36, 37, 38, 39 we updated our model with the assumption that some of the harm rates do not remain constant over the time horizons.Despite numerous efforts to define a state of euhydration and determine the daily water requirements of children, men, women, and older adults, no empirical research provides definitive answers and no universal consensus exists.Moreover, studies conducted on gerbils have shown food hoarding to increase activation of cells containing tyrosine hydroxylase, which catalyzes rate-limited dopamine synthesis, in subcortical regions of the brain .Use this free water intake calculator daily to track your hydration goals and maintain optimal health.The method was built on previous studies that used PRTs in humans 27,28,29,30,31,32,33.The 10% weight loss was net beneficial for all specific treatments; however, similar to the combined GLP-1 RAs, achieving a 5% weight loss did not exceed the harms for any of the specific treatments.In a randomized controlled trial, Griffioen-Roose et al. compared the LFPT with other measurements of desire for different foods and sensory-specific satiety .The daily water AI range of the NAM corresponds to plasma AVP levels well below 2.0 pg/ml, likely because the NAM proposed that human water requirements should not be based on a “minimal” intake , as this might eventually lead to a deficit and possible adverse performance and health consequences . Effectiveness of GLP-1 Medications However, all RCTs showed that weight reduction stablizes over time after the initial 1 or 2 years of treatment. Such decisions could be enhanced by extending the benefit-harm approach to develop decision support aids. This would help to optimise the benefits, reduce treatment (mis)overuse, and improve resource allocation for those who truly need the treatments. The preference-sensitivity of the net benefit underscores the importance of personalised treatment decisions considering individual patients' preferences and values, in addition to their outcome risks and treatment goals. Eating fewer foods means there’s an increased probability you won’t get in as many nutrients as you need.For those who are affected, reducing weight by just 5-10% can improve risk factors and …Pharmacological stimulation via glucagon-like peptide-1 receptor agonists (GLP1RAs) has become an essential tool for the treatment of type 2 diabetes mellitus (T2DM).Effects are dependent on agent potency and dose, and typically include various upper GI (nausea, vomiting) and lower GI (diarrhea, constipation) symptoms.2,3 Notably, participants receiving placebo in these trials often also report significant rates of these symptoms, and between-group differences in cessation due to intolerable adverse effects remain low.3 In addition to slower dose uptitration, various toolkits have been developed to assist in tolerability, as highlighted and summarized in the text and figures of a recent review.10While the significantly decreased volume of food consumed by patients leads to decreased caloric intake, gastric bypass surgery also causes notable changes to gut hormone levels .Labeling certain foods as “bad” and telling yourself that they are off limits often increases cravings and focus on those foods, sometimes leading to overeating when you finally allow yourself to indulge.The systematic reviews showed that GLP-1 RAs effectively reduce weight in people living with obesity (but without diabetes), particularly in the initial years of treatment.We’ll be the first to admit that water can be very refreshing but after a while, it can also become very monotonous.An estimated 5 million Americans are now incorporating these drugs into their weight-loss strategies, underscoring their transformative impact and accessibility.The snack boxes were weighed before and after consumption to determine the composition of the food consumed by the participants. Talk with your healthcare provider or registered dietitian to personalize your plan and achieve your goals. Combining GLP-1 medications with a balanced, strategic meal plan can help you maximize results while minimizing side effects. These foods are often low in protein and essential nutrients, making them less helpful for achieving your nutrition targets. High-fat and high-sugar foods, for example, may trigger nausea or other digestive issues. This calculator provides general guidelines for healthy adults.We assigned 0.25 for the relatively more serious outcomes, including alopecia, cholecystitis, cholelithiasis, and pancreatitis.Without the biological drive to achieve a lower body fat mass, there appears to be no physiological demand for changes to appetitive behaviors.Novo Nordisk advances early-stage obesity medication, amycretin, to phase 3 clinical development based on early-phase clinical trial results in people with obesity or excess weight, published in The Lancet.Using the Leeds Food Preference Task, the Blundell group found participants taking semaglutide craved a smaller number of foods, with a decrease in the implicit preference for high-fat, non-sweet foods in particular .In this study, energy density was measured as the amount of energy or calories in a particular weight of food (kcal/g). Compiling a range of data from six studies that reported 22 different observation days 10,13,16,18,54,64, we plotted the relationships between TWI and the primary brain-regulated variable (POSM), the neuroendocrine response (plasma AVP) to changes of POSM, and the resulting changes in urine volume and concentration. Currently, copeptin is just beginning to be used in clinical settings during randomized control trials evaluating changes in water intake and disease 104,105. Although a plasma AVP concentration is useful because it represents the sum of all factors that influence pituitary AVP release (Table 5) and AVP turnover in the circulation, we acknowledge that other hormonal/neurological biomarkers (e.g., angiotensin II, aldosterone) also play a role in water homeostasis. In one Table 7 experiment , participants (5 ♂ & 3 ♀, 26–50 years) rehydrated with tap water (10 ml/kg, 620–870 ml) after a 24-h water restriction; 60 min after this water consumption, the average plasma AVP decreased from 3.3 to 1.5 pg/ml, suggesting that subjects had reached a state of euhydration. However, when these test subjects underwent water restriction for 12h and 24h, a stronger neuroendocrine response was observed (i.e., representing hypohydration) as plasma AVP levels of 2.9–3.5 pg/ml in young adults and 8.3 pg/ml in older adults. Fact: Protein, Fat, and Fiber Provide Satiety, Too We predicted the absolute effects of the positive and negative outcomes over 1 and 2 years of treatment using exponential models. The benefit of Glucagon-like Peptide-1 (GLP-1) receptor agonists (RAs) in weight reduction against potential harms remains unclear. For each of the 10 designs (we even have a bullet journal style!), there is a daily, weekly, monthly, and yearly version available so you can track your water intake over any period you prefer as you establish and eventually keep this habit going. To make it easy to track your daily water intake, we’ve created 40 Free Printable Water Trackers for you to use and keep easily accessible! Comparison of recommended Adequate Intakes a for water, published by European and American health organizations. This report defined the minimum water requirement in general terms as the amount of water that equals water losses and prevents adverse effects of insufficient water such as dehydration. Similar to the NAM report (above), however, the EFSA report stated that a single water intake cannot meet the needs of everyone in any population group because the individual need for water is related to caloric consumption, the concentrating-diluting capacities of the kidneys, and water losses via excretion and secretion. The link between anti-obesity medications and bariatric surgery, particularly gastric bypass, is strengthened by evidence of gastric bypass increasing gut hormone secretion and activity. Additionally, participants could be influenced by a social desirability bias and respond by altering their reports to reflect behaviors that are deemed more socially acceptable . Verbal reports as a means of gathering information on ingestive behaviors are often used ; however, verbal report comes with an array of challenges that reduce the validity and reliability of the data obtained. Additionally, it is important to consider food preference as a separate variable which describes a subject’s food choice based on their personal enjoyment and satisfaction. We also evaluate the tools and techniques used to study these dimensions, and recommend future directions for further research. Using the Leeds Food Preference Task, the Blundell group found participants taking semaglutide craved a smaller number of foods, with a decrease in the implicit preference for high-fat, non-sweet foods in particular . Liraglutide’s effect on slowing gastric emptying has been suggested as an explanation for higher satiety levels and decreased appetitive behavior, albeit the mechanism of this hypothesis has not been demonstrated . Liraglutide also directly stimulates proopiomelanocortin neurons, and this has been postulated to result in reduced hunger and appetitive behavior 50, 51. A 10% weight loss outweighed harms at both 1- and 2- year horizons with probabilities of 0.99 and 0.97, respectively. In the sensitivity analysis assuming decreasing rates for harm outcomes (see methods), the probability of net benefit generally improved, as reflected in Fig. Incidence of achieving a 10% (or 5%) weight loss per 1000 people over 2 years without worrisome harms. The LFPT is uniquely able to simultaneously measure explicit liking and implicit wanting of participants, but does not account for variation in food preferences which may present across different times in a day. However, responses from study participants are subject to individual interpretation of scale ratings and introduce an element of subjectivity to acquired results. The Drinkometer assesses multiple crucial variables of ingestive behavior, but the short duration between sucks and bursts limits opportunities to extract detailed analyses of interval measurements. For instance, the UEM provides opportunities for dynamic consumption pattern measurements, but restricts investigators to a single set of food items under a laboratory setting. It was reassuring that no major differences were found between the verbal report measures and the direct measures of behavior 45, 70, 71. Similar plasma AVP concentrations have been published in a study of LOW (TWI, 0.74 L/24h) and HIGH (TWI, 2.70 L/24h) by Perrier and colleagues . We interpret these data to mean that the brain did not attempt to conserve water when TWI was ≥3.2 L/24h, and that the water requirement of these healthy young women existed between 1.6 and 3.2 L/24h. The experimental design involved 3 d of baseline observations, 4 d of modified water intake (during which LOW consumed the TWI which HIGH habitually consumed, and vice versa), and 1 d of ad libitum water intake. Central, autonomically-controlled changes of plasma AVP concentration (i.e., at the border of euhydration and mild hypohydration; Figure 3) also act to maintain optimal health and functions in normal persons. Thus, the data in the upper right quadrants of panel A and panel B correspond to intense neuroendocrine responses and a rigorous defense of total body water; the data in the lower left quadrants correspond to minimal-to-moderate defense of total body water. Your weight, exercise data, and calculation results remain entirely on your device. In very hot climates or during heatwaves, you may need 20% more water than in moderate temperatures. Drink small amounts frequently rather than large volumes at once, and pay attention to your body's thirst signals. However, long-term adherence in a real-world setting is challenging, and termination of obesity medication results in weight regain towards pre-treatment body weight. This is significant because increasing evidence shows that chronically elevated plasma AVP (likely due to an insufficient daily TWI) could contribute to a number of negative health outcomes. Urine volume (UVOL), plasma osmolality (POSM), urine osmolality (UOSM, 24h), and plasma AVP plotted against daily total water intake. The components of 24-h water balance in Table 3 have contributed to international recommendations regarding the daily water intake required for good health (Table 1). Not all these methods (column 1, Table 2) have contributed in meaningful ways to organizational recommendations regarding the daily water intake required for good health (Table 1). These two investigations were theoretically connected by the fact that AVP is secreted in response to high plasma osmolality (i.e., low water intake) and acts via V2 receptors in renal nephrons, increasing translocation of the aquaporin 2 channel and facilitating increased water reabsorption . Shortly thereafter, it was confirmed that an inverse relationship existed between self-reported water intake and the development of hyperglycemia, during a nine-year longitudinal surveillance study . Based on an apparent dose-response relationship between copeptin and severity of the metabolic syndrome , the important work of Enhörning and colleagues described a significant positive association between the baseline plasma copeptin concentration of healthy adults and their odds of developing impaired fasting glucose and/or diabetes during the five-year observation period. There is only one way to find out and that is by tracking your daily water intake! Pharmacological stimulation via glucagon-like peptide-1 receptor agonists (GLP1RAs) has become an essential tool for the treatment of type 2 diabetes mellitus (T2DM). Additionally, men with type 2 diabetes exhibited deteriorated glucose control and increased plasma cortisol following three days of water restriction . Historically, low daily water intake, in the absence of symptoms and outside of athletic pursuits, has been considered to be innocuous because theoretically it was balanced by increased AVP secretion, enhanced renal water reabsorption, increased water consumption, and maintenance of water balance . During exercise, you should drink water before, during, and after your workout. Individual hydration needs can vary based on age, gender, health conditions, medications, and lifestyle factors. This calculator provides general guidelines for healthy adults. This accounts for your body's metabolic needs, physical activity, and environmental conditions. Several measurement tools have been adapted to measure variables of food behavior in humans, and each must be carefully considered with their strengths and limitations to develop optimal investigations. Additionally, verbal reports have been primarily used to examine food intake, which can be susceptible to subjectivity. Glucagon-like peptide-1 (GLP-1) analogs are approved for the treatment of obesity in adults and adolescents. Novo Nordisk advances early-stage obesity medication, amycretin, to phase 3 clinical development based on early-phase clinical trial results in people with obesity or excess weight, published in The Lancet. High-fat and high-sugar foods, for example, may trigger nausea or other digestive issues.A 5% weight loss did not show a net benefit, with probabilities of 0.13 and 0.01 at year 1 and year 2, respectively.Thus, the primary purpose of the present manuscript is not to modify current AIs but rather to provide novel additional perspectives regarding 24-h TWI, euhydration, and human water requirements.Studies have shown remarkable results for those using GLP-1 drugs for weight loss.The EFSA determined AIs on the basis of population statistics, utilizing calculated ‘free water reserve’ (ml/24h) ; this quantity is defined as the difference between the measured urine volume (ml/24h) and the calculated urine volume necessary to excrete all urine solutes (i.e., obligatory urine volume, mOsm/24-h) at the group mean value of maximum UOSM 1,11.To avoid the risk of double counting and overestimation of harms, we halved the weights to 0.05 specifically for the gastrointestinal-related harm outcomes (such as abdominal pain, constipation, diarrhoea, dyspepsia, eructation, flatulence, nausea, upper abdominal pain, and vomiting) that may be correlated.Thus, the outcome risks from the RCTs may not be well reflective of the true risk distributions in the general population with overweight or obesity. Simply enter your body weight (in kilograms or pounds), select your daily exercise duration, and choose your climate condition. If you have kidney disease, heart conditions, or other medical concerns, please consult with your healthcare provider before making significant changes to your water intake. Our free online water intake calculator is a comprehensive hydration tool that helps you determine your optimal daily water consumption based on multiple factors. Enter weight and exercise time to get your daily water requirement When people lose significant amounts of weight (considered around 10% or more of body weight loss), they will lose muscle mass, too. In that way, the body’s natural GLP-1 “doesn’t have its same oomph,” Undeberg says.Indeed, multiple animal investigations and human genetic studies have described the role of V1a receptors in glucose regulation and dysfunction 140,141,142.However, it is ultimately crucial to investigate objective measures of food intake to better clarify the effect of anti-obesity medications.The macronutrient profile of foods selected by individuals taking semaglutide may change as shown in a randomized trial by Blundell et al. .The printables below are not just great water trackers but are also part of our Companion Planner, in which you can pair many of the printables on our website with some of our free calendars to make your own Companion Planner.Everything you need to lose weight, manage side effects, and stay consistent – Recipe books, workout plans, mindset programs and more!Body Mass Index (BMI) is a simple yet effective way to assess your weight relative to your height.Although the incidence of most harm outcomes was consistent across the specific GLP-1 RAs, some were specific, such as alopecia (observed in tirzepatide) and cholecystitis (observed only in tirzepatide and liraglutide), leading to between-treatment variations in net benefit (Table 2).The second purpose of the present manuscript is to increase awareness of the importance of daily water intake, because a considerable percentage of individuals in industrialized countries consume less than the 24-h water AI that is recommended for their life stage.This accounts for your body's metabolic needs, physical activity, and environmental conditions. The study also explored other potential adverse effects, such as bowel obstruction, and found higher rates in patients taking GLP1RAs versus those taking bupropion/naltrexone. This expert analysis reviews the role of GLP1RAs in cardiovascular (CV) health and risk of gastrointestinal tract (GI) adverse effects. These advances have prompted the American Diabetes Association (ADA), American Association of Clinical Endocrinology (AACE), and other professional societies to update clinical practice guidelines and recommend use of these agents in patients with diabetes mellitus (DM) and established cardiovascular disease (CVD) regardless of hemoglobin A1c concentrations, including consideration as first-line pharmacotherapy. Of 1000 persons treated with GLP-1 RAs for 2 years, 375 (95% confidence interval 352 to 399) achieved a 10% weight loss, and 318 (296 to 339) achieved a 5% weight loss compared to those treated with placebo.Furthermore, several studies have reported a strong correlation between plasma AVP and copeptin levels in healthy individuals 98,101 and patients 102,103 across a wide range of POSM.Since its inception, the UEM has been adapted for broader human or animal studies to assess food intake patterns related to GLP-1 analog treatment.Blundell et al. used verbal reports and the Leeds Food Preference Task (LFPT) to examine changes in the choice of diet composition of adult humans with obesity and without diabetes .The expanding use of GLP1RAs for chronic weight management in individuals without DM has spurred interest in CV implications in the population without DM.However, it is widely accepted that the brain constantly acts to preserve homeostasis via neuroendocrine responses which defend set points of body water volume and concentration .However, as evidence on the topic is accumulating rapidly, there is a need for continuous evaluation and monitoring of the benefit-harm balance to guide up-to-date decisions. The benefit outcome was achieving a weight loss of ≥5% or ≥10% from baseline, each considered as separate end points in the analysis. Our target population was people aged 18 years or older without diabetes, with body mass index (BMI) of ≥30 kg/m2 or ≥27 kg/m2 in the presence of at least one weight-related comorbidity, including hypertension, dyslipidemia, obstructive sleep apnoea, or CVD. We performed a literature search and synthesized data using pairwise meta-analysis to estimate the effect of GLP-1 RAs on the various outcomes to inform the benefit-harm balance modelling. The study did not require informed consent or ethical approval, as we used all published data. We assumed that some outcome rates would remain similar during the first three months of treatment initiation, followed by a gradual decrease over the following consecutive 3-month periods until the end of the first year, with decline rates by 10%, 40%, and 50%, respectively. Some of them could be more frequent during the initial treatment, and subsequently decline due to the tolerance and attenuation of the placebo effect. Firstly, guided by insights from some of the RCTs,34, 35, 36, 37, 38, 39 we updated our model with the assumption that some of the harm rates do not remain constant over the time horizons. Tools to measure ingestive behaviors Together, these effects make it easier to manage hunger, reduce calorie intake, and make healthier food choices, all supporting sustainable weight loss.We additionally calculated the probability that individuals obtained a net benefit from GLP-1 RAs from the distribution of the benefit-harm index.National Academy of Medicine (NAM) publication, which presented dietary reference intakes for water , included a lengthy review of water balance studies and water needs (i.e., using the stable isotope of water D2O) of children and adults (Table 1).Additionally, participants could be influenced by a social desirability bias and respond by altering their reports to reflect behaviors that are deemed more socially acceptable .“When oats are combined with water, they can be filling,” Collingwood says.Semaglutide resulted in reduction of body weight of up to 15% over 12–18 months in adults and adolescents with obesity .The interface adapts to your screen size, making it easy to calculate your daily water needs on the go.Muscle is the magic when it comes to shaping your body, revving your metabolism, and supporting long-term results. Excess body water may reduce plasma AVP to a level below the sensitivity of present-day technologies (i.e., most immunoassays detect AVP to ≥0.5 pg/ml; , making it difficult to distinguish over-hydrated states from a normal euhydrated state (1.0–1.8 pg/ml; Table 7). In terms of the water requirements of normal individuals, determining the intensity of the body’s defense of total body water and tonicity (e.g., measuring changes of plasma AVP or regulated variables) provides a laboratory method to assess the intensity of homeostatic responses and the response thresholds which the brain employs. In normal adults, an increased intensity of neuroendocrine response (i.e., which defends the volume and concentration of total body water) results in decreased urine volume and increased urine osmolality, secondary to increased plasma AVP (Figure 4, panel B). Increasing POSM signifies increasing perturbation of homeostasis; whereas an increasing plasma AVP concentration represents an increased intensity of neuroendocrine response and indicates that the brain is regulating body water via the kidneys. A proposed schematic of a method to assess human daily water requirements by measuring the intensity of neuroendocrine responses that are employed by the brain to defend homeostasis of body water volume and concentration. The introduction of the highly potent incretin receptor agonists semaglutide and tirzepatide has marked a new era in the treatment of type 2 diabetes and obesity. By addressing both weight loss and physical appearance, you can feel healthier and more confident in your skin. On average, patients can lose 15-20% of their body weight within months when the medication is combined with a healthy lifestyle, including proper nutrition and exercise. Allowing enjoyable foods in moderation, like a few times per week, can help reduce cravings and the food noise that can interfere with your weight-loss goals. Better blood sugar and insulin balance can make weight loss easier. We performed the first comprehensive assessment of the benefit-harm balance, particularly for the initiation of GLP-RAs for rapid weight loss reduction. The trade-off between the benefits and harms of GLP-1 RA treatment is challenging due to the multitude of parameters and outcomes to consider concurrently. However, the net benefit decreased significantly when greater weight (i.e., concern) was placed on harm outcomes such as nausea due to their high frequency (Fig. 2b). Most moderately severe harm outcomes had less impact on the net benefit due to their lower frequency and/or less precise effects (AppendixSupplementary Fig. S3). The corresponding absolute net benefit were estimated to be 208 (204–220), 32 (28–40), and 20 (12–28) per 1000 people achieving the 10% weight loss without experiencing any worrisome harms. The macronutrient profile of foods selected by individuals taking semaglutide may change as shown in a randomized trial by Blundell et al. . The group receiving semaglutide verbally reported lower cravings for dairy and starchy foods and less desire to eat salty or spicy foods, along with less difficulty controlling eating and resisting cravings. However, these effects can be attenuated by starting with lower doses of the medication and gradually titrating to the recommended dose . We chose 0.60, instead of 0.50, to ensure a certain benefit since the net benefit at a probability of 0.5 would be zero. Cumulative events of positive and negative outcomes were predicted using exponential models for GLP-1 RA-treated and untreated groups assuming constant outcome ratets over the time horizons. To assess whether empirical aggregate preferences are necessary or if individual patient preferences should be used in decision-making, we additionally conducted the analysis with wider ranges of preference values for selected outcomes (see sensitivity analysis). We assigned 0.25 for the relatively more serious outcomes, including alopecia, cholecystitis, cholelithiasis, and pancreatitis. The GLP-1 medications can lower appetite for food and thirst for liquids. Eating enough fiber from plant foods is important for a few reasons, including to help minimize the slowdown in GI function. The amount of protein will be different for each person based on their age, gender, weight, height and activity level. We already have the diet mapped out for people who lose a lot of weight through bariatric surgery, and this is much the same advice given to someone on a GLP-1 medication. Yes, our water intake calculator is completely free to use. By using our water intake calculator regularly, you can maintain optimal hydration levels throughout the day. Dietitians can help with meal planning to maximize nutrition and help diagnose or prevent nutrient deficiencies — all things to help people reach their weight management and health goals. This connection supports the feasibility of using investigations of ingestive behavior following gastric bypass surgery as models for similar studies upon anti-obesity medication treatment. This prompts further investigation and clarification of the mechanisms promoting weight loss, including their effect on ingestive behavior and food preference. Pharmacological intervention is increasingly utilized due to promising weight loss effects, minimal invasiveness, and sustainability. Even a modest weight loss of 5-10% of your body weight can lead to significant health improvements, such as better blood pressure, cholesterol levels, and blood sugar regulation. By increasing GLP-1 levels, you can better support weight loss and diabetes management. Therefore, this study aims to shed light on current research regarding the effect of GLP-1 analog pharmacotherapy on food intake and behaviors, their limitations and opportunities to expand, and methods used to assess these dimensions. Reports have emerged that the weight loss effect of these medications may be related to changes in food preferences and ingestive behaviors following the treatment. While significant weight loss brings numerous health benefits, it’s important to prepare for potential changes in your body’s appearance. This can lead to difficulties in activities of daily living like climbing stairs, getting in and out of a car, taking care of oneself and even increase the risk of falls. Performing some type of resistance training like weightlifting is especially good, since it has a muscle-building effect. Muscle will always be lost as well, and this can have a negative long-term impact on our health. To minimize post-ingestive effects, reinforcers are of minimal volume and calories so that the ingestion of a food reward may not lead to premature satiety and interfere with the oral-based evaluation. Moreover, studies conducted on gerbils have shown food hoarding to increase activation of cells containing tyrosine hydroxylase, which catalyzes rate-limited dopamine synthesis, in subcortical regions of the brain . Ghrelin injections in hamsters stimulate long-term food hoarding, highlighting a major neurochemical factor in appetitive behavior . Siberian hamsters which were administered neuropeptide Y (NPY) injections to the hypothalamic paraventricular nucleus and perifornical area displayed marked increases in food hoarding, highlighting it as a key regulator of appetitive behavior . Food hoarding as an appetitive behavior has been extensively studied in non-human primates with laboratory animals exhibiting increased hoarding following food deprivation . This fact is significant in terms of long-term health outcomes because a growing body of epidemiological evidence shows that chronically elevated plasma AVP ( likely due to an insufficient daily TWI) is related to cardiovascular, obesity and cancer morbidity and mortality, as well as the regulation of glucose metabolism. The main outcomes analyzed from each study are the impact of GLP-1 analogs on ingestive behavior, cravings and craving control, and differential effects in the weight loss and weight maintenance phase. Thus far, studies have primarily explored the weight loss phase and report decreased short-term appetite and food intake upon treatment. First, because the drugs analysed are relatively new indications in the treatment of overweight and obesity, we could not find sufficient evidence for all the harm outcomes chosen in the analysis. Our analyses show that GLP-1 RAs used for weight reduction in people with overweight and obesity result in a net benefit in achieving a 10% weight loss during the initial phases of treatment, particularly in the first and second year. Therefore, this review focuses on semaglutide and liraglutide and aims to explore current discoveries of their effect on ingestive behavior. Lilly’s bimagrumab boosts weight and fat loss when added to Novo's Wegovy. Looking ahead, WuXi AppTec will continue to leverage its global R&D and manufacturing network, along with its unique, fully integrated, end-to-end CRDMO model, to empower the development of next-generation GLP-1 drugs and bring meaningful benefits to patients worldwide. Combination therapies that pair GLP-1 receptor agonists with agents that help preserve muscle mass are being developed to not only reduce fat tissue but also maintain lean body mass. Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily. Thus, understanding the neurobiological mechanisms that alter behaviors to determine food intake is fundamental to understanding the association between appetitive behaviors and consummatory behaviors. Leveraging this understanding could help refine anti-obesity treatment to benefit clinicians and patients. To better understand these mechanisms, it is imperative to consider objective measurements of food intake in future studies. Elucidating the relationship between GLP-1 analogs and ingestive behavior could reveal additional parameters which contribute to their anti-obesity effects. This strategy could provide more meaningful long-term outcomes and improved quality of life for patients seeking to lose weight. GLP-1 based therapies have already demonstrated remarkable efficacy in treating type 2 diabetes and obesity. Holst, J.J. GLP-1 physiology in obesity and development of incretin-based drugs for chronic weight management. I provide details regarding the development of GLP-1 receptor agonists for anti-obesity therapy and discuss the possible mechanism behind their beneficial effects on adverse cardiovascular events. Observational studies demonstrate that 19–71% of adults in various countries consume this volume of water or less each day 13,109,110. Our examination of data from multiple research studies (Figure 6) demonstrates that a plasma AVP concentration of 2.0 pg/ml is equivalent to a TWI of 1.8 L/24h. The dynamic complexity of the water regulatory network, and inter-individual differences, are the primary reasons why widespread consensus regarding the daily water requirements has not been reached to this date. Despite numerous efforts to define a state of euhydration and determine the daily water requirements of children, men, women, and older adults, no empirical research provides definitive answers and no universal consensus exists. “When oats are combined with water, they can be filling,” Collingwood says. These all slow the movement of food through the digestive tract and are foods that increase GLP-1. Weight loss also leads to a decrease in GLP-1 and changes other appetite-related hormones, which can prompt you to eat to get back up to your baseline weight. In that way, the body’s natural GLP-1 “doesn’t have its same oomph,” Undeberg says. In addition, people who have obesity may not get as big of a release of GLP-1 after eating. Furthermore, a plasma AVP threshold ˂2.0 pg/ml corresponds closely with the euhydrated baseline values shown in Table 7 (1.0–1.8 pg/ml), as observed in four groups of men and women. Considering the plasma AVP threshold which indicates an obvious neuroendocrine response (~2.0 pg/ml ; Figure 4), LOW were above this threshold when consuming a TWI volume of 1.6–1.7 L/24h whereas HIGH were above this 2.0 pg/ml AVP threshold only when their TWI was modified to 2.0 L/24h on days 4–7. The morning plasma AVP levels in Figure 5 were similar (LOW, 1.4–1.5 pg/ml; HIGH, 1.1–1.3 pg/ml) when both groups were consuming a similar high TWI (LOW, 3.5 L/24h; HIGH, 3.2 L/24h). Figure 5 depicts plasma the AVP concentrations of free-living LOW and HIGH during one morning laboratory visit on each of 8 days. This method for assessing 24-h water balance also can be applied to the TWI of free-living adults. In this post, we'll deep dive into the discussion around GLP-1s and eating disorders, to ensure that employers, providers and health plans have access to the right support for members on GLP-1s. For those who are affected, reducing weight by just 5-10% can improve risk factors and … You don’t need brutal workouts, calorie panic, or gym guilt to transform your body. Grab the GLP-1 Muscle Protection Program and start building the body that keeps up with your goals.