A rigorous reference search was performed for all included studies to determine if any additional studies could be added to this review. Each article was independently reviewed by two reviewers during title/abstract and full-text screening to determine study eligibility. Additionally, studies were excluded if the articles were not in English and if no full text was available. The paucity of comparative head-to-head trials prevents a definitive conclusion of the superiority of one GLP-1 RA over another. GI adverse effects are the predominant adverse effect of this class and have been demonstrated in the results of every GLP1RA trial. BN can reduce body weight, inhibit inflammatory reactions, directly be excreted by the kidney, and have fewer adverse reactions. This suggests that BN may be an effective treatment for obesity and NASH (42). As the first original research drug in the field of diabetes in China, it has been recommended for meal injection and approved for the hypoglycemic intervention of T2DM (40), especially for patients with poor blood glucose control by metformin alone. However, the mechanism of GLP-1R in treating obesity is still uncertain, and more clinical evidence is needed for its long-term safety and efficacy. Overview of Efficacy, Side Effects, and Key Challenges Thus, STEP 2 has a greater proportion of men (49.1%) than the other trials (19.0–25.9%). While the STEP 2 trail included 51% female participants , the STEP 1, STEP 3 and STEP 4 trials included 73%, 81% and 79% female participants, respectively 15–17. The underlying reasons for the weaker response for both GLP-1 RAs in people with diabetes compared to cohorts without diabetes are unclear, although there are some hypothetical explanations . Glucagon-like peptide 1 (GLP-1)-based therapies, such as semaglutide and tirzepatide, represent highly effective treatment options for people with type 2 diabetes and obesity, enabling effective control of glucose and weight loss, while reducing cardiovascular and renal morbidity and mortality.This study developed pharmacodynamic models for 12 GLP-1RA drugs and conducted quantitative analyses of their time-course relationships, dose-response relationships, factors influencing efficacy, dropout rates, and adverse events.GLP-1RA can be used in patients with hepatic impairment, without dose adjustments, although they have not been extensively studied in these circumstances (71).A significant disadvantage of using these medications is the high rate of weight regain when they are discontinued.Once started, the dose should be increased every four weeks (or weekly if using liraglutide) until maintenance dose is achieved (Table 1).Known under the brand name Wegovy, semaglutide is FDA-approved for obesity management and comes with a maximum prescribed dose of 2.4 mg. A separate double-blind study assessed exenatide's effect on intracranial pressure in women with idiopathic intracranial hypertension . In osteoporosis, GLP-1 RAs such as exendin-4 can help by increasing osteocalcin levels, a protein essential for bone health. For instance, liraglutide has been shown to reduce oxidative stress in macrophages through GLP-1 receptor signaling . The United States Food and Drug Administration (FDA) approved it to treat obesity. The indication is to effectively reduce glycosylated hemoglobin levels in patients with T2DM by reducing fasting and postprandial blood glucose levels (61, 62). Lipotoxicity induced by saturated free fatty acids plays a vital role in renal injury in obese patients (49). Using weekly semaglutide, prandial insulin was discontinued in all patients, and basal insulin was discontinued in 7 out of 10 patients. Overall, a meta-analysis of RCTs showed that A1c reductions were −0.28%, −0.21%, and −0.17% for liraglutide 1.8, 1.2, and 0.6 to 0.9 mg, respectively, and −0.17% for exenatide (62). Because these studies allow for concomitant insulin adjustments, and they lack a controlled group (i.e., placebo) interpretation of the A1c reduction is very difficult. It is possible that some of those patients were in honeymoon period, or had an alternative diagnosis, such as ketosis-prone diabetes or latent autoimmune diabetes in adults (LADA). The wide use of these drugs and their adverse effects, although rare, need to be considered and calculated by patients who are using the drugs for weight. This will also help the insurance companies in the long run since taking these anti-obesity medications will significantly improve the patient's overall health and lower the risk of complications caused by obesity. Similarly, a study found a significant reduction in LDL-C following treatment with liraglutide 1.8 mg/day (-0.44 mmol/L) and exenatide 10 µg twice a day (-0.40 mmol/L) . In a different diabetic neuropathy model, the combination of oral amitriptyline and subcutaneous liraglutide and a formulation combining both drugs showed significant improvements in pain and inflammation markers in the sciatic nerve . Another study found that liraglutide also reduced the activation of microglial cells in the brain's cortex and thalamus in diabetic rats by lowering the expression of NLRP3 protein, a marker of inflammation in brain microglia . These treatments helped alleviate hypersensitivity in various pain models, including those for formalin-induced, nerve injury-induced, bone cancer-induced, and diabetes-induced pain in both mice and rats . However, BMI remained unchanged, indicating that the intracranial pressure effect was likely a direct action of exenatide rather than weight loss alone. In recent years, there has been an increase in the morbidity, disability rate,and mortality due to obesity, making it great threat to people’s health and lives, and increasing public health care expenses. Additional studies are needed to describe changes in dietary patterns and diet quality in individuals using GLP-1 or GIP/GLP-1 RAs, including macronutrient and micronutrient intake. Nonetheless, there is a paucity of data on the adequacy of protein intake for maintenance of muscle mass and function or intake of essential vitamins and minerals for overall health. Why Diet Matters with GLP-1 Medications However, this technique is impractical in the clinical setting and it is mostly used for research purposes. Indeed, peripheral insulin level was the strongest determinant of insulin resistance in this study. Indeed, peripheral insulin levels are ~2-fold higher in patients with T1D compared to patients matched for hyperglycemia (33). In subjects without type 1 diabetes, insulin is secreted from the pancreas into the portal vein, where 50-80% of insulin is metabolized in the first hepatic pass. Fruits and vegetables may also be prioritized, along with reduction of energy intake, and provision of fiber, vitamins, and minerals. As we await guidelines and further research results, clinicians should discuss the importance of balanced nutritional intake with all patients prescribed GLP-1 and GIP/GLP-1 RAs and provide access to an RDN whenever possible. A guideline from the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and The Obesity Society was published in 2014, but recently approved pharmacological treatments for obesity were not included . Other potential contributors to low muscle mass include fat accumulation in the muscle, mitochondrial and stem cell dysfunction, weight cycling, physical inactivity and inadequate intake of energy and protein 2,39,40. Risk for muscle loss increases as people age, especially in those with diabetes, who also have an increased risk for sarcopenia 36,37. We’re here to support your benefit strategy and your employees’ health goals. Serious side effects could occur in rare cases, including pancreatitis or gallbladder problems. We usually start with a low dose and slowly increase it to help your body adjust. Approximately half of participants were female (53%), 88% were White, 92% had type 2 diabetes and 86% had obesity. To understand body weight changes at 72 weeks after index dispense date, we used descriptive statistics to compare participants with and without weight data in the 72-week time window. A Poisson mixed models with robust error variance was used to estimate the proportion of participants who lost at least 5% of their baseline body weight, with follow-up time as a discrete fixed effect. Mixed models were also used to test for linear and quadratic trends in weight loss and proportion with at least 5% weight loss over time. Thus, all clinicians prescribing GLP-1s for obesity management should establish a thoughtful plan of care that includes thorough nutritional and lifestyle counseling before, during, and after the weight reduction period.Such knowledge is needed to guide optimal nutritional support for patients undergoing treatment with GLP-1 or GIP/GLP-1 RAs.One of the primary criteria for qualifying for GLP-1 weight loss drugs is your body mass index or BMI.They are contraindicated in pregnancy, in patients with a personal or family history of medullary thyroid cancer or multiple endocrine neoplasia syndrome type 2.7 Some suggest that it not be used with patients with a history of pancreatitis as there have been rare cases reported.The authors recommend future studies to assess the protein and essential micronutrient intake change following GLP-1 or GIP/GLP-1 interventions and include a registered dietitian nutritionist (RDN) in the expert team.For instance, in one observational study, a larger reduction in added sugars and a greater increase in dietary protein were seen among participants receiving GLP-1s plus dietary counseling compared to GLP-1s alone.156In this narrative review, we have explored the varying effects of these agents on essential metabolic parameters such as blood glucose, cardiovascular health, weight management, blood pressure, and lipid profile in both diabetic and non-diabetic patients. During GLP-1 use, nutritional and medical management of gastrointestinal side effects is critical, as is navigating altered dietary preferences and intakes, preventing nutrient deficiencies, preserving muscle and bone mass through resistance training and appropriate diet and complementary lifestyle interventions. Challenges include side effects, especially gastrointestinal; nutritional deficiencies due to calorie reduction; muscle and bone loss; low long-term adherence with subsequent weight regain; and high costs with resulting low cost-effectiveness. Use our handy online calculator to check your body mass index (BMI) and find out if you're a healthy weight Discover the differences between Saxenda vs Mysimba weight loss treatments. The OMA advises healthcare professionals conduct pre-exercise medical evaluations and provide suggestions regarding types and recommended amounts of dynamic (aerobic) training, resistance (anaerobic) training, and leisure time physical activities for patients seeking obesity treatment . These patients were not necessarily pursuing weight reduction through calorie restriction, therefore, intake may be even less while pursuing weight reduction. This narrative review describes studies quantifying and characterizing dietary intake in people with obesity and/or T2DM who were taking GLP-1 or GIP/GLP-1 RAs, as compared to those on other treatments or placebo. Glucagon-like peptide receptor agonists (GLP-1RAs) and dual mechanism GIP/GLP-1 RAs are effective for promoting weight reduction and for improving glycemic control, which has led to heightened usage by people with obesity and/or T2DM. This narrative literature review summarizes clinical studies quantifying and characterizing dietary intake in people with obesity and/or T2DM using GLP-1 or GIP/GLP-1 RAs. There have also been ongoing shortages of some of the doses of the medications. The cost can be prohibitive, most insurances require prior authorization and making patients aware of this up front helps reduce frustration and phone calls/messages. Liraglutide is daily, while semaglutide and tirzepatide are weekly. Every person is unique and so is each treatment plan.There are several other types of diabetes medications, like oral (taken by mouth) medications.Evidence-based analysis allows patients to understand treatment outcomes and potential complications.After treatment, serotonin reuptake transporter (SERT) increased, while tryptophan hydroxylase-1 (TPH-1) decreased in the colon, showing that exendin-4 may reduce pain by regulating SERT and TPH-1 levels.We have treated 1000s of patients in the UK and helped them reach their weight loss goals, creating healthier and happier lives in the process.With the potential for delayed gastric emptying absorption of other medications should be considered.6 Most of the drug interactions are increased risk of hypoglycemia therefore education about symptoms is important.The increase in the prevalence of obesity has been concomitantly linked with an increase in the prevalence of T2DM .STEP 1 and STEP 2 were designed to have Asians as at least 10% of the population and have a greater proportion of Asians than the other trials .Potential benefits need to be weighed against the risk of hypoglycemia and lack of long-term data. Of note as well, if a patient is undergoing a non-emergent surgery, newer anesthesia consensus-based guidance recommends holding GLP-1s up to a week in advance given possible gastroparesis leading to aspiration risk.18 If a patient is undergoing a surgery, it may be best to have anesthesia give guidance on their preference of preoperative GLP-1 management. It also allows continued documentation of weight to demonstrate success with the weight loss efforts. With the potential for delayed gastric emptying absorption of other medications should be considered.6 Most of the drug interactions are increased risk of hypoglycemia therefore education about symptoms is important. In the STEP trials there was no notable increase in the incidence of acute pancreatitis with the 2.4mg dose of semaglutide.6 Although rare, hypoglycemia, acute kidney injury, angioedema, and anaphylaxis have been reported. A multi-agonist approach is a likely road for the future of anti-obesity drug development involving novel receptors such as glucagon and amylin possibly with even more profound weight loss 286,287. However, available studies are only seen in rodent studies, but the additive or synergistic effects of GLP-1 and GIP on hunger and satiety require further clinical research . Recent studies have now demonstrated the strongest weight loss effect with the dual agonist for GLP-1 and GIP, upwards of 22% over 1 year . However, earlier studies showed inconsistences of GIP as a cause of weight loss, although more recent studies have demonstrated increased weight loss efficacy 280,281,282,283. Studies suggest that GLP-1 drugs are not a direct cause of depressive symptoms in weight loss . How to diet effectively Drugs like Ozempic, Wegovy, Zepbound and Mounjaro have been around for years, but they’ve recently been making headlines due to a rise in popularity as weight loss agents. This should include an emphasis on healthful eating, physical activity, and resistance training; screening and management around substance use disorders, eating disorders, mental health, and sleep; and micronutrient or protein supplementation as needed. This new proposed paradigm more closely aligns with clinical goals and practice around obesity care. That expert group recommended using BMI as a surrogate measure of clinical obesity for population-level assessments. With promising therapeutic effects comes an increased scrutiny on side effects. However, the expanding adoption of GLP-1 receptor agonists also brings with it a set of challenges and complications. Finally, as the study included only English-language publications, there may have been a publication bias. Such knowledge is needed to guide optimal nutritional support for patients undergoing treatment with GLP-1 or GIP/GLP-1 RAs. Moreover, given the vital role that protein plays in maintaining muscle health and function, the quantity and quality of protein intake is especially important to monitor. This study concluded that control of eating questionnaire scores significantly improved with semaglutide along with significant decreases in cravings for salty, spicy, dairy, and starchy foods. Finally, Silver et al. used 24-h recall to compare dietary intake and reported a greater reduction in total and added sugars and greater increase in protein in the dietitian-guided caloric restriction group compared to the medication-alone group . Quast et al. had no control group, instead comparing ad libitum intake between groups on 2 different GLP-1RAs (liraglutide and lixisenatide). Understanding GLP-1/GIP: A Guide to Dual-Action Weight Loss Treatments Technological devices enable patients to record their medication adherence and adverse effects, thereby allowing clinicians to quickly monitor how certain meal plans are being tolerated. Clinicians who prescribe GLP-1 RAs should monitor body composition, vitamin B12, iron, and renal indices every four to eight weeks.6 Regular reviews of interacting agents, especially weight-promoting or nephrotoxic tablets, are also essential.6 As a result, diets for people with diabetes prescribed GLP-1 RAs often favor gradual deficits, low-glycemic carbohydrates, and consistent protein intake to maintain optimal glucose levels. Your healthcare provider will tell you when and how often to take your medication (usually injections). Overweight is when you have a BMI of 25 to 29.9. Obesity is a chronic condition in which you have a body mass index (BMI) of 30 or higher. There’s a low risk of mild low blood sugar (hypoglycemia) episodes if you take a GLP-1 agonist. If you become pregnant while taking the medication, see your healthcare provider immediately. GLP-1 agonists aren’t safe to take during pregnancy. Some people form antibodies to GLP-1 agonists, particularly with exenatide. These side effects are more likely to happen when you start the medication or if you’re taking an increased dose. These symptoms improve with continuous use, as only 3% and 9% of patients reported nausea with the long- or short-acting GLP-1RA after 6 months of use, respectively (72). Titration of GLP-1RA based on the individual’s response in weight and glycemic control is recommended. Only in the ADJUNCT trials an increase in ketotic hyperglycemia events were reported with these dose adjustments (56, 57). Patients should be aware of these potential unwanted effects and, to minimize loss of muscle mass, encouraged to participate in resistance exercises and increase protein intake . It is important to note that these studies mostly included dipeptidyl peptidase-4 DPP4 and early GLP-1s, exenatide, and liraglutide. Rapid weight loss can also lead to what is known as an “Ozempic face”, where the cheeks become hollowed out, and wrinkles, as well as eye bags, become more pronounced. GLP-1 medications can cause a range of side effects related to the gastrointestinal system as well as changes in muscle mass and effects on the appearance of the face and loss of hair (Figure 2). Obesity and T2DM are interrelated clinical conditions with overlapping etiologies and pathophysiology . Obesity and type 2 diabetes mellitus (T2DM) are increasingly common in the United States (US), as in other developed countries worldwide 1,2. Obesity and type 2 diabetes mellitus (T2DM) are increasingly common in the United States and worldwide. No new safety signals were identified comparing participants with diabetes to non-diabetic cohorts . The rates of these adverse events across SCALE and STEP trials were comparable between GLP-1 RAs and placebo. You have weight-related health conditions Newer strategies for weight maintenance have focused on preserving or even increasing lean body mass to counteract the decreases in energy expenditure thereby allowing for sustained weight loss 105,263. Other studies have found little to no impact of physical activity on maintaining weight loss . The Pennington symposium highlighted potential alternative approaches for nutrition management that may be beneficial for weight loss maintenance. Most effective weight loss from a dietary standpoint is seen over 3 to 6 months, with at least one-third of patients regaining lost weight within the first year and the majority of patients regaining the weight after five years 224,225. However, as detailed in this review, calorie reduction generally leads to short-term weight loss, with poor success rates for long-term weight loss maintenance. However, the increasing reliance on pharmacological solutions over lifestyle interventions reflects a broader societal trend that risks de-emphasizing the role of diet and exercise in managing chronic diseases. GLP-1 receptors are expressed in the pancreas, which has led researchers to hypothesize that these drugs may influence pancreatic function in ways that could predispose certain individuals to inflammation. Although the absolute risk is low, pancreatitis can be severe and even life-threatening. Pharmacological treatments for weight loss have expanded and, while GLP-1 agonists are the focus of this review, other choices are available and summarized here. These include favorable effects on heart and brain health and decreased diabetes risk 55,56. GLP-1 receptor agonist drug therapy is a key focus with consideration of the mechanism of action, clinical trials in weight management, and the potential role of the drug category in weight maintenance. The discovery of the gut hormone glucagon-like peptide-1 (GLP-1) and the synthesis of agonists for its corresponding receptor (GLP-1 receptor) has tremendously impacted treatment for weight reduction. Others tolerate the drug but, once meaningful weight reduction is achieved, do not wish to stay on the medication for life. In the authors’ clinical experience, some individuals have challenges with side effects, out-of-pocket costs, or changes in payer coverage. Questions include dose-specific effects of single nutrient, food, and dietary pattern interventions; targeting multiple enteroendocrine pathways simultaneously; potential differences in subgroup responses (e.g., with insulin resistance or obesity); and effects of prebiotic, probiotic, and symbiotic therapies.268,272 Nutrition insecurity was more common among adults with younger age, lower income, lower educational attainment, and identifying as Black, Hispanic, or Native American/indigenous compared with White backgrounds.246 Adjusting for age, sex, race/ethnicity, income, education, and food security status, individuals experiencing nutrition insecurity were 40-60% more likely to have obesity as well as type 2 diabetes, heart disease, hypertension, and hypercholesterolemia. These results showcase the ability of semaglutide to be a treatment option for cardiovascular benefit, notwithstanding the glycemic index. Various CVOT trials, such as the SELECT, SUSTAIN, and SOUL trials, have demonstrated varying effects on heart diseases over the years 13,39,46. Following the promising results of the REWIND trial, FDA approved Trulicity (Dulaglutide) in those with T2DM who either have cardiovascular disease or are at increased risk of the disease to be used preventively for reduction in MACE . Konig et al. in their post hoc analysis summarized that dulaglutide caused a significant reduction of 16.7% in HBA1c and 25.4% in UACR, which, in turn, contributed to the benefits recorded for cardiovascular health 43,44. GLP-1 medications are not approved for use during pregnancy or while breastfeeding. Our team evaluates your past and current efforts to lose weight and works with you to build a plan that combines medication with lifestyle interventions. You may be a strong candidate if you’ve been consistently following a healthy eating plan and staying active without significant or lasting results. Common GLP-1 medications include Semaglutide (sold under brand names like Wegovy and Ozempic) and Tirzepatide. You’ve tried everything—cutting carbs, counting calories, following intense workout plans—only to see minimal results or gain the weight back. In clinical studies, LIXI has shown the benefits of weight loss, which is well tolerated by patients and can meet the needs of overweight patients for weight control.Nutrition insecurity was more common among adults with younger age, lower income, lower educational attainment, and identifying as Black, Hispanic, or Native American/indigenous compared with White backgrounds.246 Adjusting for age, sex, race/ethnicity, income, education, and food security status, individuals experiencing nutrition insecurity were 40-60% more likely to have obesity as well as type 2 diabetes, heart disease, hypertension, and hypercholesterolemia.This includes reduced food preoccupation or “food noise,” reduced emotional eating, less external eating (i.e., eating that responds to external triggers, irrespective of satiety), and fewer binge eating episodes.56,149 Similar effects have been observed on eating control, sweet cravings, and symptoms of food addiction.147,Tirzepatide can uniquely induce weight loss beyond what is achieved with selective GLP-1 agonists alone.The exact risk change with other histological subtypes of thyroid carcinoma is yet to be fully established.For both diabetic and non-diabetic patients, the drug can reduce weight (97, 98). Another question for future research is whether intake differs for patients using GLP-1 or GIP/GLP-1 RAs for obesity management versus diabetes management. To date, some studies report lower intake of certain micronutrients in people with obesity , , , but future studies need to examine risk of worsening nutrient status following use of anti-obesity medications and protocols. To fill existing research gaps, we recommend future studies to examine not only the quantitative change in calorie intake but the qualitative changes in macro- and micronutrient intake including dietary patterns for patients using highly effective anti-obesity medications. A significant reduction in body weight should be seen as a target for treatment of type 2 diabetes . However, higher levels of weight loss of ≥ 15% were achieved almost exclusively by participants with diabetes who received liraglutide or semaglutide, whereas this outcome has not been attainable by any other glucose-lowering intervention or with lifestyle intervention alone. Although specifics of lifestyle programming for weight reduction and maintenance vary across guidelines, common foundations include a nutrient-dense, reduced-calorie diet; a structured program of physical activity; and behavioral strategies to support lifestyle change.94 Various dietary patterns have been used with success, with adherence to counseling visits and the selected diet often being the important factors in determining outcomes.101 Specific nutrient goals can vary by age, sex, and life stage (e.g., infancy, childhood, adolescence, pregnancy, lactation, older adulthood)102 as well as comorbidities or clinical conditions.The maximum weight reduction effect ranged from 4.25 kg (Liraglutide) to 22.6 kg (Retatrutide).Ongoing clinical trials in peripheral vascular disease, neuropsychiatric and substance use disorders, metabolic liver disease, arthritis, hypertension and neurodegenerative disorders may broaden indications for GLP-1-based therapeutics.Next, data synthesis was performed using a meta-analysis for single-arm trials, categorized by subgroup, to determine the overall mean and 95 % CIs for each subgroup.A 30-week randomized non-inferiority study comparing 2 mg once-weekly EX-LAR with 10 µg twice-daily EX in 295 patients with T2DM.After the use of GLP-1 RAs, obese and diabetic patients, respectively, demonstrated a 16.6- and a 13.7-point improvement in the KCCQ-CSS scale.Longitudinal studies should investigate how these agents impact long-term health outcomes, such as the incidence of cardiovascular diseases and mortality.It is worthwhile to point out that a weight loss plateau is often stated with the assumption that additional weight loss is desired, but difficult to achieve. Among the studies that provided data on the percentage of participants discontinuing treatment due to AEs, this ranged from 0% to 9%. Among these patients, 78% experienced a decrease in weight while undergoing GLP-1 RA therapy. Possible reasons mentioned included the saturation of the primary healthcare system, which may have prevented patients from receiving their monthly follow-ups. This prospective study examined patients who were administered GLP-1 RAs during the initial titration phase. In this study, the majority of the patients had various significant past medical histories, including pancreatitis, dyslipidemia, and hypertension. While some of the trials reported a decrease in appetite as a side effect, like the ADJUNCT trials (53–58, 60), it should be noted that this is one of the main mechanisms of action of these drugs to achieve weight loss. In a meta-analysis with patients with T1D, weight loss with liraglutide 1.8 mg was estimated at ~5 kg compared to placebo (62), and there was a dose-response effect. In ‘real-world’ studies weight loss was significant after 12 months and 3 years of treatment (50, 51). A small, short study had two patients on liraglutide with positive postprandial C-peptide at baseline completely discontinued insulin treatment with good glycemic control (63). Due to the potential loss of lean body mass with the use of GLP-1 and GIP/GLP-1 RAs, the OMA advises baseline body composition analysis with reassessment at regular intervals, if there is a substantial weight reduction in a short period of time, or if weight reduction is considered to be excessive 58,59. Clinical practice guidelines also exist for patients pursuing obesity treatment via bariatric devices and surgery . More recently, the efficacy of newer generation anti-obesity medications was reviewed, but nutrition management protocols were not included . The Obesity Medicine Association (OMA) publishes management guidance on nutrition, physical activity, behavioral therapy, and pharmacotherapy, including anti-obesity medications , , . While agents from the GLP-1 and GIP-1/GLP RA classes are advised for treatment of T2DM and overweight/obesity, specific dietary needs for this population are not discussed . GLP-1 agonists affect the way your body signals hunger and digests food. Maximum safe doses depend on your health condition, other medications, and how well you tolerate the drug. The best diet while taking semaglutide focuses on lean proteins, vegetables, whole grains, and healthy fats. Following these GLP-1 food guidelines helps you reach your weight loss goals while maintaining good nutrition and avoiding digestive issues. Safe weight loss on semaglutide happens gradually at about 2 pounds per week. Lean proteins, fiber-rich vegetables, and complex carbs support weight loss while preventing uncomfortable side effects. This natural feedback helps develop healthier eating habits that support long-term weight management. Exercise helps preserve muscle mass during weight loss and can improve how your body responds to the medication. Highly processed foods and certain beverages can interfere with your weight loss goals and worsen side effects. Interestingly, weight loss was greater in patients who experienced these AEs compared to those who did not, but these indirect effects led to only a small proportion of total overall weight loss . Tirzepatide’s advantage is via its dual agonism decreasing hyperglycemia and appetite significantly more than other GLP-1 RAs, possibly leading to its improved reductions in body weight compared to semaglutide . Tirzepatide showed a significant reduction in weight loss compared to semaglutide which may be attributed to its ability to act as a dual agonist of GLP-1 and gastric inhibitory polypeptide (GIP) receptors. Similarly, in this study, semaglutide produced a greater numerical weight loss compared to the other GLP-1 RA active comparators except for tirzepatide. A 2021 network meta-analysis found a significant dose-dependent weight loss of semaglutide 0.5 and 1 mg compared to 0.6 mg liraglutide, but not in comparison to 1.2 and 1.8 mg liraglutide . Grade I-A is an indicator of the recommendation and its level of evidence, here denoting that the procedure or treatment should be performed/administered and has strong evidence that it is useful/effective. The current US list price for GLP-1s for obesity ranges from ∼$12,000 to $16,000 per year.2 Full costs may be incurred by those who self-pay, due to either off-label use or no payer coverage. Less common side effects included dyspepsia, fatigue, headache, eructation (belching), hair loss, gastroesophageal reflux, dizziness, and gastritis (Table 2). GLP-1s delay gastric emptying, leading to bloating, fullness, and nausea.43 GLP-1s activate several brain regions responsible for weight regulation, appetite, and nausea.51 Occasionally, GLP-1s affect intestinal motility or secretions, contributing to diarrhea.46 Higher doses are more likely to provoke these adverse symptoms, indicating a dose-dependent relationship.40 Combining GLP-1s with metformin does not appear to worsen GI side effects, despite metformin’s association with similar symptoms.50 Evidence-based analysis allows patients to understand treatment outcomes and potential complications. This medication activates both GLP-1 and GIP receptor pathways, producing enhanced weight reduction compared to single-agonist alternatives. Physicians commonly prescribe Ozempic off-label for weight loss applications. This cardiovascular indication represents the first such approval for any weight loss medication. Clinical studies document decreased overall energy consumption with GLP-1 medications, facilitating calorie deficit maintenance. Clinical guidelines on obesity management, including the 2013 American Heart Association/American College of Cardiology and the 2016 American Association of Clinical Endocrinologists/American College of Endocrinology guidelines, highlight the importance of a structured lifestyle intervention program.8 These programs typically include a calorie-restricted diet, increased physical activity, and behavioral therapy, which together are recommended as the first-line treatment for individuals with overweight or obesity. Lifestyle interventions, alternative anti-obesity medications, and bariatric surgery offer different approaches for weight loss and may provide useful context for evaluating the overall impact of GLP-1 RAs. Additionally, observations of weight regain after treatment discontinuation and reductions in lean mass highlight the need for long-term, individualized strategies to sustain clinical benefits. This study provides a quantitative evaluation of the efficacy and safety of GLP-1RAs and offers valuable insights into the assessment of new drugs for weight reduction. At 52 weeks, weight reduction effects were 7.03 kg, 11.07 kg, and 24.15 kg for mono-agonists, dual-agonists, and tri-agonists, respectively. Thus, future studies should compare different GLP-1 RAs to better outline the most optimal and safest formulation of GLP-1 RAs for weight loss. Much of the recommended annual weight loss diets often seen in US News and World Report reflect a variety of these dietary patterns, highlighting that diets are more than their nutrient content . Dietary advice historically has seen energy restriction as the foundation for weight loss. Treating obesity has evolved in recent years, with various shifts in dietary, pharmacological, and surgical strategies available for the management of obesity . The cardiometabolic consequences of obesity such as insulin resistance, glucose intolerance, type 2 diabetes, arterial hypertension, atherosclerosis, and dyslipidemia are all stressors on the heart and vascular system 18,19. Nausea and gastrointestinal adverse effects were reported in about half of patients with T1D on liraglutide (56–58). Of note, not all studies focused on overweight or obese patients, with many allowing patients with BMI ≥20 kg/m2. Weight loss was similar in patients on CSII, with a mean weight loss of 6.3 kg (55). Some people tolerate tirzepatide better due to its dual hormone action, while others find semaglutide gentler on their digestive system. People with type 2 diabetes may benefit more from metformin, while those with hormone imbalances might prefer sermorelin therapy. Your current health status significantly influences which alternatives are appropriate. Non-prescription GLP-1 alternatives like metformin offer affordable options, while newer therapies may require higher out-of-pocket costs through telehealth providers. Recent studies show GLP-1 drugs like liraglutide improve insulin sensitivity independently of weight reduction.With the brand name Saxenda, liraglutide is another GLP-1 agonist used for weight loss.Compared with liraglutide, semaglutide has been subjected to some minor structural changes that resulted in greater efficacy and gained pharmacokinetic properties that allow once weekly dosing of semaglutide vs. once daily administration of liraglutide .EX long-acting preparation can reduce weight, but there are few related clinical studies, and most focus on patients with T2DM.Individuals with obesity are also more likely to have suboptimal dietary patterns at baseline that predispose them to nutrient deficiencies prior to starting therapy, for example, due to high ultraprocessed food consumption or highly restrictive diets.60 Obesity itself can also increase risk of nutrient deficiencies at baseline due to alterations in nutrient absorption, distribution, metabolism, or excretion.61 All these issues highlight the importance of proactively managing dietary composition and quality to maximize nutrient intake within a lower-calorie intake.58The most recent randomized, open-label, phase 3 b trail, STEP 8, directly compared semaglutide, 2.4 mg, vs. liraglutide, 3.0 mg, for weight management in adults with overweight or obesity to rigorously assess differences in efficacy and adverse event profiles .Others tolerate the drug but, once meaningful weight reduction is achieved, do not wish to stay on the medication for life.With modern research, a growing body of evidence highlights the possible use of GLP-1RAs to reduce major adverse cardiovascular events (MACE) and improve overall outcomes in diabetic or obese patients. Approaches to address and support the ability of individuals to achieve long-term success with their overall weight management program are a critical area for future implementation research. Just as occurs following GLP-1 discontinuation, weight regain is common with waning adherence to dietary and physical activity weight loss interventions. Standardized clinical workflows that incorporate structured programs of stepped therapy, supported by nutritional and lifestyle interventions, could also help promote more effective and cost-effective use for individuals and healthcare systems. Reducing weight by 5 % or more significantly improves obesity-related health complications . The FDA has approved glucagon-like peptide-1 (GLP-1) receptor agonists such as Liraglutide, Semaglutide, and the GLP-1/gastric inhibitory polypeptide (GIP) dual agonist Tirzepatide for the treatment of obesity. Finally, there was notable heterogeneity in the patients included across the studies as well as the dose regimen variants observed. What are GLP-1 weight loss drugs? These successful subjects with weight loss maintenance reported high levels of physical activity, high levels of dietary restraint, low calorie, and fat intake, and low levels of overeating (loss of control of eating or disinhibition) . In this study population, 88% were able to keep 10% of their body weight off at year 5 and 87% at year 10. To participate in the study, weight loss greater than 30 pounds had to have been maintained for more than 1 year at the time of enrollment. It is interesting to note that an extension study of semaglutide was performed to 120 weeks, but treatment was discontinued at 68 weeks. It is worthwhile to note in both studies all participants were prescribed a reduced calorie (500 kcal/day deficit) and increased physical activity 150 min/week) regimen, which was insufficient to help preserve the initial weight loss. However, many studies fail to establish a causative relationship between treatment and symptoms, suggesting that GLP-1 RAs have a favorable safety profile. Administering liraglutide once a day found a significant reduction in TL from the baseline (-0.20 mmol/L) . Unlike LDL-C and HDL-C, more studies found that GLP-1 RAs such as liraglutide and exenatide significantly decrease TL 51,67,68. Ozempic, originally formulated for diabetes management, and Mounjaro have shown considerable effectiveness through appetite suppression mechanisms, establishing their utility as weight loss interventions. GLP-1 drugs for weight loss, including Wegovy® (semaglutide) and Zepbound® (tirzepatide), function by replicating natural hormones that control hunger signals and blood glucose levels. Jensterle et al. (145) presented the primary outcomes of clinical trial programs called SCALE and STEP and studies on the efficacy of GLP-1R agonists in pediatric obesity. Recently, several multi-targeting agonists of GIPR, GLP-1R, or GCGR for treating T2DM and obesity have been in clinical trials. 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 expanding use of GLP1RAs for chronic weight management in individuals without DM has spurred interest in CV implications in the population without DM. Beyond glycemic control, the results of cardiovascular outcome trials (CVOTs) have demonstrated these agents' efficacy in lowering rates of major adverse cardiovascular events (MACE) in patients with T2DM, which remain the leading cause of death and complications in this population. With the right combination of herbs, nutrients, and probiotics, you can naturally support your body’s GLP-1 production, helping you feel fuller, balance blood sugar, and improve metabolism without the side effects. They found herbs, nutrients, and probiotic strains that have been studied for decades and can either mimic GLP-1’s effects or boost your body’s own production of this satiety hormone. Bariatric surgery is the most effective antiobesity management strategy characterized by average of 30–40% weight loss, but it comes at a cost of irreversibility, surgery-related complications and considerable percentage of late complications . While some patients with diabetes achieved ≥ 5 or 10% with placebo, higher levels of ≥ 15% in patients with diabetes were achieved almost exclusively with those who received liraglutide or semaglutide and not by those on placebo 20–22. In patients with diabetes, both efficacy benchmarks were achieved by semaglutide , while the efficacy of liraglutide did not meet the criteria in mean difference between active product vs. placebo 20, 21. Proportion of patients with ≥ 5% weight loss from baseline for liragutide and/or semaglutide vs. placebo. Figure 3 demonstrates the proportion of patients with ⩾ 5% of weight loss from baseline for liragutide and/or semaglutide vs. placebo. Obesity is a major global epidemic, defined by the World Health Organization (WHO) as “an excessive accumulation of body fat that may impair health” 1,2. There was a significant negative correlation in the exponential pattern between age and weight reduction effect, whereas baseline weight and BMI had no significant impact. The maximum weight reduction effect ranged from 4.25 kg (Liraglutide) to 22.6 kg (Retatrutide). This systematic review of public databases included placebo-controlled randomized clinical trials of GLP-1RAs. The paucity of comparative studies prevents a definitive conclusion of the superiority of one GLP-1 RA over another. Health equity can be defined as a state in which everyone has a fair and just opportunity to attain their highest level of health,233 and health disparity is a particular health difference linked with economic, social, or environmental disadvantage, often adversely affecting groups of people who have systematically experienced greater social or economic obstacles. Because FIM programs can help overcome multiple barriers to healthful eating, including cost, time, access, and knowledge, they could play an important role in achieving better as well as more equitable short- and long-term outcomes with GLP-1 therapy—a critical area for further investigation. Supportive measures include electronic health record screening for food and nutrition security, curricular and accreditation interest in medical nutrition education, and expanded care pathways and reimbursement models.231 State Medicaid programs, Medicare Advantage payers, commercial payers, the Veterans Health Administration, and the Indian Health Service are all implementing and evaluating various FIM programs. Food is Medicine (FIM) programs are structural interventions in healthcare that offer food-based nutritional therapies as part of an individual’s plan to manage or treat specific disease conditions and, often, social needs.231 These are prescribed by a clinician, tailored by an RDN to relevant medical conditions, and covered by health insurance. Tailored solutions can help address these challenges, which require healthcare provider knowledge and sensitivity and identification of individuals more likely to experience digital challenges (e.g., older adults).230 Obesity has become a significant global health burden (15), and patients with T1D, who were historically characterized as lean, are nowadays found to be overweight or obese with increasing frequency in clinics. This likely responds to the fact that patients with T1D were excluded from large randomized, controlled trials (RCTs) assessing cardiovascular and renal outcomes with the use of these drugs (7, 8, 11). Recent American Diabetes Association (ADA) guidelines recommend GLP-1RA for weight management in T2D, and also GLP-1RA as first-line therapy in patients with T2D and established cardiovascular disease (13). The Semaglutide Treatment Effect in People with Obesity (STEP) trials evaluated the safety and efficacy of semaglutide for weight loss. To date, there are two GLP-1s approved for weight loss; liraglutide (Saxenda) and semaglutide (Wegovy), and one GLP-1 and gastric inhibitory polypeptide also know as glucose-dependent insulinotropic polypeptide receptor agonist (GIP), tirzepatide (Zepbound). Clinical research and studies uniformly demonstrate their ability to contribute to notable weight loss, improve lipid profiles, lower blood pressure, and reduce cardiovascular risk. The study by Frias et al. compared semaglutide against varying doses of tirzepatide. The blinding of participants and personnel as well as the blinding of outcome assessors showed a high risk of bias for five studies and a low risk of bias for two studies, respectively. The sequence generation showed a low risk of bias across five studies with two studies demonstrating an unclear bias. To assess the qualities of the studies as well as the risk of biases present within the studies, the MINORS and Cochrane Risk of Bias criteria were used given the inclusion of both RCT and non-RCT studies. In current clinical trials, the maximum administered doses of these drugs are 0.6 mg, 200 mg, 10 mg, 12 mg, 45 mg, and 2.4 mg, corresponding to 70.8 %, 66.4 %, 65.8 %, 60.7 %, 75.2 %, and 77.3 % of their respective Emax values. Thus, apart from modifying the specificity of drugs to receptors, enhancing their affinity can significantly improve the weight reduction outcomes of GLP-1RA drugs. For example, among GLP-1 mono-agonists, Liraglutide had a relatively lower weight reduction effect (4.03 kg), whereas Orforglipron had the highest effect (8.66 kg). The results indicate significant variability in the efficacy of these drugs in reducing body weight. Impact of age on the weight reduction effects of Liraglutide (A) and Semaglutide (B) It can be used as a primary treatment for obesity, as an alternative for patients who do not qualify for bariatric surgery, or as a bridge to surgery . For Contrave, a weight loss plateau seems to occur for all the COR studies around 32 to 36 weeks with overall weight loss around 8 to 9%. Admittedly, the lesser potency of these drugs in the initial weight loss phase often overshadows their potential for usage for weight loss maintenance purposes. Perhaps the least successful of the FDA-approved weight loss drugs in terms of achieving weight loss maintenance is Orlistat (tetrahydrolipstatin). It is estimated that around 80–90% of patients will develop an adverse effect from the use of this class. In addition to nausea and vomiting, other GI-related side effects include diarrhea, constipation, dyspepsia, decreased appetite, and abdominal pain 158,159,160. The most often reported side effects are nausea and vomiting which are a result of activation of specific GLP-1 receptors in the hindbrain and these symptoms can be mitigated with gradual dose escalation 155,156,157. Arguably, the arrival of semaglutide more than five years later sparked the public’s attention to GLP-1 agonist therapy. The interindividual variability in antiobesity efficacy is one of the most important challenges, because there are currently almost no reliable predictive models to assess the weight reducing potential at the individual level. Compared with liraglutide, semaglutide has been subjected to some minor structural changes that resulted in greater efficacy and gained pharmacokinetic properties that allow once weekly dosing of semaglutide vs. once daily administration of liraglutide . The next generation GLP-1 RA semaglutide 2.4 mg is the latest anti-obesity medication, approved by the FDA in June 2021. GLP-1 agonism with current GLP-1 RA and emerging novel combined anti-obesity compounds represents a benchmark for future pharmacological anti-obesity treatment. 5. Subgroup analysis of receptor specificity GLP-1 RAs’ distinct and unique mechanism of enhancing insulin release in response to glucose, increasing satiety, and slowing gastric emptying can be attributed to the previously mentioned benefits of weight management and glycemic control. Most patients found ROSE-010 preferable to prior treatments, with female patients responding more effectively. In another study, liraglutide alleviated LPS-induced visceral pain in rats by decreasing intestinal inflammation and IL-6 in the colon through nitric oxide response . This is where one needs to advocate for insurance coverage of these drugs and to lower the prices as much as possible to achieve lasting patient compliance and help serve our patient communities better . At the same time, they may be covered by insurance for T2DM, but they should be covered for other chronic diseases such as obesity. The factors that contribute to this behavior include poor or no health insurance coverage, limited access to newer medication, financial distress, poor health education and communication, and physician bias. In addition, it was observed that those who took less than 80% of their prescribed statin therapy versus patients who completed their therapy had a 45% increase in all-cause mortality and a 15% increase in CVD events, suggesting that completion of therapy is crucial . Furthermore, in an internet survey of former statin users, 60% reported SAMSs, and 62% reported discontinuation of statin due to side effects . Tirzepatide has demonstrated total lean mass loss as well, although additional studies are needed to determine the impact of this 134,182. While these cosmetic findings are an issue, the loss of lean body mass is another area of concern . The large and long-duration GLP-1 cardiovascular outcome trials did not show an increase in pancreatitis . Despite this, animal studies have demonstrated decreases in pancreatic secretion in response to GLP-1 elevation, therefore the mechanism behind this potential interaction of GLP-1 receptor analogs and pancreatitis remains elusive . In fact, the package insert for semaglutide suggests an increase of 13% for amylase and 22% for lipase and the dual incretin agonist tirzepatide suggests a 38% increase and lipase upwards of a 42% increase . After weekly subcutaneous injection, EX was slowly released from the microspheres by diffusion and microsphere rupture and reached a stable plasma concentration about 6-8 weeks after treatment (114). Therefore, during DUL treatment, we should pay close attention to the related signs of pancreatitis, and if pancreatitis occurs, we need to stop the drug immediately (113). It is worth mentioning that in the AWARD-2 study, there were several cases of pancreatitis caused by DUL (112). It is approved for treating hyperglycemia in patients with T2DM in many countries (105, 106). Semaglutide demonstrated increased numerical weight loss compared to dulaglutide, liraglutide, and exenatide. GLP-1 RAs have shown efficacy in reducing body weight in diabetic patients with minimal to moderate observed AEs. Fourth, the follow-ups for several studies were short-term and may not accurately capture weight loss and AE outcomes in the long term. Therefore, the goal should be assessing the patient’s overall health goal rather than a percentage or numerical weight loss number. Among the plethora of treatment options available, clinicians must take into account comorbidities, cardiovascular benefits, AE risks, impact on weight, cost, and patient preferences to optimize treatment plans and patient outcomes . Dietary supplements can be proactively considered for at-risk nutrients, such as vitamin D, calcium, B12, or a multivitamin-mineral tablet, at appropriate doses and tailored to each person’s needs. For some individuals, this can cause inadequate nutrient intake; for others, it may contribute to rebound preferences for sugars and refined carbohydrates if they delay eating until they are overly hungry. Some report food aversions, sometimes severe, typically at the initiation of treatment and with dose increases. In contrast, GLP-1 side effects such as nausea may trigger cravings for comfort foods containing sugars or refined carbohydrates such as white flour and white rice. Anecdotal reports also suggest a reduction in taste enjoyment and cravings for ultraprocessed foods and an increase in preferences and cravings for minimally processed, nutrient-dense foods like fruits and vegetables.155 Dietary counseling may modify these changes. An expert group comprising multiple clinical and research disciplines appraised the scientific literature, informed by expert knowledge and clinical experience, to identify and summarize relevant topics, priorities, and emerging directions. In recent weeks the new type 2 diabetes drug Tirzepatide has been hitting the headlines in the UK, but is it something we should be taking too much notice of? PrivateDoc can help you lose weight and keep the weight off for good. Unboxing your Saxenda medication, find out more on how to use it, and what to expect from your Saxenda treatment. Individuals with obesity are also more likely to have suboptimal dietary patterns at baseline that predispose them to nutrient deficiencies prior to starting therapy, for example, due to high ultraprocessed food consumption or highly restrictive diets.60 Obesity itself can also increase risk of nutrient deficiencies at baseline due to alterations in nutrient absorption, distribution, metabolism, or excretion.61 All these issues highlight the importance of proactively managing dietary composition and quality to maximize nutrient intake within a lower-calorie intake.58 In the trials, GI symptoms rarely led to discontinuation, with 49 Fewer data are available on the impact of GI side effects on adherence in clinical practice. For example, hemoglobin A1c reduction can occur without weight change, and reduced risk of cardiovascular events appears to emerge before substantial weight reduction.38,39 Compared with LIXI, LIR is more effective in improving blood glucose and reducing weight, and both treatments are well tolerated (75, 77, 78). However, iGlarLixi patients had more gastrointestinal-related adverse, primarily nausea (16.9% vs. 0.8%) in this 26-week, randomized, open-label study (70). A prospective clinical study from Spain found that besides controlling blood glucose (fasting blood glucose and glycosylated hemoglobin), LIXI can also improve blood lipids, especially total cholesterol and triglyceride (68). The primary adverse reaction to EX is nausea, suggesting that nausea may be the primary mechanism of weight loss (52). However, consumption of ultraprocessed food has been shown to induce an even greater consumption of calories, and therefore leads to weight gain. This can be attributed to the metabolic adaptations that are seen to occur in those with obesity. It is worthwhile to note these variables are all related to appetite, hunger, and caloric intake. As expected, there was weight regain, but there still was an overall 5.6% net loss of weight by the end of 120 weeks . When switched to placebo there was invariably weight regain, implying that the loss of inhibition of hyperphagia drove this process. The most recent randomized, open-label, phase 3 b trail, STEP 8, directly compared semaglutide, 2.4 mg, vs. liraglutide, 3.0 mg, for weight management in adults with overweight or obesity to rigorously assess differences in efficacy and adverse event profiles . Figure 2 shows the changes of mean body weight from baseline for liragutide or semaglutide vs. placebo in the phase 3 trials designed to assess an antiobesity efficacy as a primary outcome. Altogether, we identified six RTC studies with liraglutide 3 mg 9–14, four RCT studies with semaglutide 2.4 mg/week 15–18 and one study that compared efficacy of semaglutide and liraglutide in participants without diabetes. Beyond the scales: Understanding healthy weight loss It has the advantages of a prolonged administration interval (once a week), few adverse reactions in the digestive tract (122), and adverse effects reported ranging from ‘mild’ to ‘moderate’ (122, 123). The early GLP-1R agonist has many defects, such as multiple injections and a high incidence of adverse reactions in the digestive tract, which limits its clinical application. Nausea and vomiting are less frequent in patients receiving EX-LAR than in patients taking EX (114). For example, one cohort study used United Kingdom claims data to examine body weight changes among 589 patients with T2D initiating a GLP-1 agonist.22 In that sample, 33% achieved weight loss ≥5% at 12 months. In addition, our results are also in line with the mean 1.6% to 4.6% differential weight loss demonstrated in placebo-controlled cardiovascular outcome trials for liraglutide 1.8mg (LEADER),17 semaglutide 1.0mg (SUSTAIN-6)18 and dulaglutide 1.5mg (REWIND).19 For example, in SUSTAIN-1, semaglutide 1.0mg achieved 4.5 kg weight loss (4.7%) while placebo achieved 1.0 kg (1.1%), a 3.6% treatment difference at 30 weeks.11 In LEAD-2, liraglutide 1.8mg achieved 2.8 kg weight loss (3.3%) versus 1.5 kg loss (2.0%) in control (metformin monotherapy), a 1.3% treatment difference at 26 weeks.12 In AWARD-3, dulaglutide 1.5mg achieved 2.3 kg weight loss (2.4%) at 26 weeks, an amount that was not statistically different from metformin.13 He suggested that adipose tissue may produce a signal that may be sensed by the brain to target a “level of body fatness”. The concept that body fat storage may be regulated was first proposed by Kennedy et al. through the concept of a “set point” . Treatments such as bariatric surgery create hesitancy among patients due to their invasiveness. Crook H, Edison P. Incretin mimetics as potential disease modifying treatment for Alzheimer’s disease. New approaches are needed to address the rising rates of overweight and obesity in the T1D population. Obesity increases the risk of microvascular and macrovascular complications, various types of cancer, and overall mortality in patients with T1D. These medications, except exenatide, are safe for patients with mild to severe renal impairment without dose adjustments (73, 74). In some of the studies, an additional 10% dose reduction was done with drug escalation. Poor food choices can make side effects worse and work against your weight loss goals. Managing your weight while taking GLP-1 medications can feel overwhelming when you don’t know which foods work best with your treatment. The best choice will depend on individual patient circumstances, and both drugs have the potential to significantly improve health outcomes for those seeking to manage their weight more effectively. Not surprisingly, food composition is often an area of question by both scientific communities and the food industry to determine the right “mix” of macronutrients to facilitate weight loss and weight loss maintenance. Even more recently in 2022, a symposium was convened to discuss the state of the science of weight loss maintenance, known as the Pennington Biomedical Scientific Symposium . Other studies confirm the importance of dietary restraint and physical activity in preventing weight regain 247,248. Randomized double-blinded placebo-controlled withdrawal studies were performed in both semaglutide and tirzepatide with crossover to placebo at 20 weeks and 36 weeks, respectively 242,243. Cessation of these drugs to see if weight maintenance could be achieved was largely unsuccessful (Table 3). A systematic search following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was performed using PubMed, Embase, and Cochrane Library for studies comparing semaglutide and other GLP-1 RAs for weight loss. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are antidiabetic drugs that have a recognized effect on weight loss. Specific formulations of GLP1RAs are indicated (semaglutide as Wegovy and liraglutide as Saxenda Novo Nordisk Inc., Bagsvaerd, Denmark) or used off-label (semaglutide as Ozempic Novo Nordisk Inc., Bagsvaerd, Denmark and tirzepatide as Mounjaro Lilly USA LLC, Indianapolis, Indiana) for chronic weight management as an adjunct to lifestyle changes. “Effectiveness of glucose-lowering medications on cardiovascular outcomes in patients with type 2 diabetes at moderate cardiovascular risk” was published in Nature Cardiovascular Research in April 2024. A recent expert group reviewed the utility of BMI-based measures for assessing individual health and concluded that these can misclassify (both underestimate and overestimate) adiposity—and thus undermine effective clinical care and policy development.271 To address this, the report proposed a new definition of clinical obesity—a chronic, systemic illness resulting from excess adiposity and characterized by alterations in tissue and organ function. Long periods of fasting without sufficient protein intake or dietary variety can lead to nutritional inadequacy, clinical nutrient deficiencies, loss of fat-free mass, and reduced resting energy expenditure.297 These effects can be mitigated through strength training, adequate protein and calories consumption, and a variety of minimally processed, nutrient-rich foods (Table 6).298 A recent simulation analysis compared continuous GLP-1 therapy vs a staged program of GLP-1 therapy until sustained weight reduction was achieved, followed by discontinuation and a structured behavioral lifestyle intervention for weight maintenance.84 With a wide range of plausible effectiveness and costs of behavioral intervention, this alternative program was projected to generate substantial savings in net healthcare costs, with minimal loss of health-related quality of life. Nearly 1 in 3 prescribed medications are never filled, and individuals regularly adhere to only half of prescribed agents.276 Evidence-based strategies to improve general medication adherence include dose simplification, patient education, electronic reminders, reduced out-of-pocket costs, and patient incentives.5,276 Integrating GLP-1 use with longitudinal, structured nutrition and lifestyle programming might also support simplified dose titration schedules and management of side effects. GLP-1 analogs and GLP-1R agonists can exert hypoglycemic effects and reduce weight. However, many anti-obesity agents that have entered human clinical trials have shown unacceptable adverse events; many of them cannot be used for more than 3 months; the curative effect is moderate and suboptimal in the long term (12). Weight-loss surgery effectively reduces weight and complications in patients with severe obesity; however, weight gain is a common complication following surgery (10). A systematic review and meta-analysis proved that weight loss had been shown to prevent and mitigate obesity-related complications (9). Please find further advice for patients and the public on treating obesity on the NHS website. The MHRA has not assessed the safety and effectiveness of these medicines when used outside of their licensed use, for example when used for weight loss in people who are not obese or overweight. In the UK, there are several licensed GLP-1 medicines including semaglutide (sold under the brand names Wegovy, Ozempic and Rybelsus), tirzepatide (Mounjaro) and liraglutide (sold under various brand names). You may see them referred to in the media as “weight loss injections” or “skinny jabs” but not all of these medicines are authorised for weight loss. Schedule a consultation today to determine if GLP-1 weight loss therapy is your next step toward lasting transformation. If you are using a GLP-1 medicine and think you might be pregnant, speak to a healthcare professional straight away. In some animal studies, GLP-1 medicines were found to be harmful to the unborn foetus, although more information is needed to see whether or not this same effect would be seen in humans. All individuals of child-bearing potential (who are able to become pregnant) using GLP-1 medications should take steps to ensure they do not become pregnant. A full list of the known side effects can be found in the product information for the individual medicines. The MHRA is reviewing any evidence for an association with other GLP-1 agonists.