Garvey et al. assessed the long-term efficacy and safety of semaglutide 2.4 mg versus placebo over 104 weeks. The review by Bergmann et al. highlighted the significant weight loss achieved with semaglutide 2.4 mg, with participants achieving ≥10% and ≥15% weight loss. Six of 16 In a study by Anam et al., the authors conducted a systematic review of RCTs to analyze the efficacy of semaglutide, a GLP-1 RA, in treating obesity . The model was validated using independent datasets, providing a useful tool for guiding treatment decisions and optimizing weight management strategies. They established an exposure-response model that quantitatively describes the relationship between systemic semaglutide exposure and weight loss, accurately predicting weight-loss trajectories . BMI is a good surveillance measure for population changes over time, given its strong correlation with body fat amount on a population level, but it may not accurately indicate the amount or location of body fat at the individual level2. Obesity treatment guidelines Concomitant use of Wegovy® tablets or Wegovy® injection with other semaglutide-containing products or with any GLP-1 receptor agonist is not recommended In medical studies, people who stopped taking Wegovy® generally regained weight.7Actor portrayals. Wegovy® pill has technology designed to facilitate absorption of semaglutide. Significant weight loss that lasts with Wegovy®1 The proportions of individuals with BMI −2 who achieved sex- and race-specific cutoff points for WC (indicating increased metabolic risk) were evaluated at week 104. The scale was calibrated yearly as a minimum unless the manufacturer certified that calibration of the weight scales was valid for the lifetime of the scale. Investigators were provided with guidelines for, and encouraged to follow, evidence-based recommendations for medical treatment and lifestyle counseling to optimize management of underlying CVD as part of the standard of care. National and institutional regulatory and ethical authorities approved the protocol, and all patients provided written informed consent. The trial protocol was designed by the trial sponsor, Novo Nordisk, and the academic Steering Committee. Wegovy® pill helped some patients achieve even more weight loss Guidelines for treating overweight and obesity in the USA place lifestyle modifications, including moderate to vigorous exercise, decreased caloric intake, and behavioral therapy, as the first steps in the intervention.1 Lifestyle modifications can reduce the risk of developing cardiovascular complications, but patients do not easily maintain any accomplished weight loss.1 If no significant changes occur through lifestyle modifications, adding pharmacotherapeutics may help to promote weight loss.1 The statistical analyses for the in-trial period were based on the intention-to-treat principle and included all randomized patients irrespective of adherence to semaglutide or placebo or changes to background medications. Thus, the study did not include Asian patients who qualify for treatment with obesity medications at lower BMI and WC cutoff points according to guidelines in their countries29. By 104 weeks, approximately 77% of SELECT patients on dose were receiving the target semaglutide 2.4 mg weekly dose, which is lower than the corresponding proportion of patients in STEP 1 (89.6% were receiving the target dose at week 68)14,21. For lower BMI classes, discontinuation rates are higher in the semaglutide group but not the placebo group.Fig. 6 depict a graded increase in the proportion discontinuing semaglutide, but not placebo. For this analysis, with death modeled as a competing risk, we tracked the proportion of in-trial patients for whom drug was withdrawn or interrupted for the first time (Fig. 6, left) or cumulative discontinuations (Fig. 6, right). The lowest tertile of the SELECT population at baseline had a mean WHtR 27, suggesting that the trial population had high WCs. Analysis of covariance with treatment and baseline values was used to estimate the treatment difference. Supplementary Table 1 outlines SELECT patients according to baseline BMI categories. The SELECT study enrolled 17,604 patients (72.3% male) from 41 countries between October 2018 and March 2021, with a mean (s.d.) age of 61.6 (8.9) years and BMI of 33.3 (5.0) kg m−2 (ref. 21). The trial product estimand data here measure the hypothetical change in body weight of patients on Wegovy® if all participants remained on randomized treatment without discontinuation or use of rescue intervention (ie, any other obesity medication or bariatric surgery). Rubino et al. investigate the effects of continued semaglutide treatment versus placebo on weight loss maintenance in adults with overweight or obesity. This study is a systematic review and meta-analysis of randomized controlled trials (RCTs) evaluating the effect of semaglutide on individuals with obesity or overweight without diabetes. Regarding efficacy data, a meta-analysis of 28 randomized, placebo-controlled clinical trials found that all four antiobesity medications met the FDA weight loss threshold of at least 5%. Clinically meaningful weight loss was evident in the semaglutide group within a broad range of baseline categories for glycemia and body anthropometrics.Concomitant use of Wegovy® tablets or Wegovy® injection with other semaglutide-containing products or with any GLP-1 receptor agonist is not recommendedPatients generally want to meet their “goal dose” quickly, to see the most progress.Secondary outcomes include the dose-response relationship of semaglutide, assessing different dosages and their impact on weight loss.They may increase weekly or decrease, depending on if you’re just getting started, or weaning off it.In the semaglutide group, 12.0% of patients achieved a BMI −2, which is considered the healthy BMI category, compared with 1.2% for placebo; per study inclusion criteria, no patients were in this category at baseline. Bucheit et al. focus on the oral formulation of semaglutide studied in the PIONEER trials, which demonstrated its efficacy in lowering HbA1c and facilitating weight loss . The study underscores semaglutide's potential as a weight loss treatment but calls for further research to confirm its long-term benefits and safety profile. The National Institute for Health and Care Excellence (NICE) has recommended that semaglutide, administered as a weekly injection to aid weight loss in overweight and obese adults, should be funded by the NHS . During the study, 30.6% of those assigned to semaglutide did not complete drug treatment, compared with 27.0% for placebo. Missing data at the landmark visit, for example, week 104, were imputed using a multiple imputation model and done separately for each treatment arm and included baseline value as a covariate and fit to patients having an observed data point (irrespective of adherence to randomized treatment) at week 104. First, SELECT was not a primary prevention trial, and the data should not be extrapolated to all individuals with overweight and obesity to prevent major adverse CV events. In the SELECT trial, patients did not enroll for the specific purpose of weight loss and received standard of care covering management of CV risk factors, including medical treatment and healthy lifestyle counseling, but without a specific focus on weight loss. Despite its promising results, the study notes limitations in the long-term efficacy and safety data and highlights potential challenges in adherence to the once-weekly dosing regimen. The study emphasizes semaglutide's potential as a weight management therapy when used alongside lifestyle changes . The study underscores the substantial weight-loss benefits of semaglutide when combined with lifestyle changes, though specific methods and limitations are not detailed in the summary provided. The 20-week duration of the study limits the understanding of long-term effects, although the short-term findings are promising . Weight and anthropometric outcomes by subgroups This literature review summarizes and discusses the weight loss results from the SUSTAIN (Semaglutide Unabated Sustainability in Treatment of Type 2 Diabetes), PIONEER (Peptide Innovation for Early Diabetes Treatment), and STEP (Semaglutide Treatment Effect in People with Obesity) clinical trial programs. Glucagon-like peptide-1 (GLP-1) receptor agonists are a class of antidiabetic medications that have shown promise in encouraging glycemic control and promoting weight loss in patients with or without type 2 diabetes. Findings confirm the chronicity of obesity and suggest ongoing treatment is required to maintain improvements in weight and health. Trial design and participants Comparing the results presented in both trials, we observe that in the primary placebo-controlled trial from the PIONEER program and SUSTAIN 1, around 40% of participants on semaglutide achieved a weight loss of 5% or more.21 31 Thus, these results could suggest that semaglutide is outperformed by phentermine-topiramate and liraglutide as antiobesity medications. This program included five trials primarily focused on comparing 2.4 mg, once-weekly, subcutaneous semaglutide with placebo treatment.11–15 This trial program did not compare semaglutide with other antiobesity medications currently on the market. Based on the SUSTAIN clinical trial program data, nausea and vomiting were minimally related to patients’ weight loss.8 The trial cited here also evaluated the primary causes of weight loss in patients taking semaglutide (Ozempic), a relatively new GLP-1 RA currently on the market only as an antidiabetic drug in both injectable and oral tablet forms. We reported in the primary SELECT analysis that serious adverse events (SAEs) were reported by 2,941 patients (33.4%) in the semaglutide arm and by 3,204 patients (36.4%) in the placebo arm (P 21. For this study, we analyzed SAE rates by person-years of treatment exposure for BMI classes (−2, 30 to −2, 35 to −2, and ≥40 kg m−2) and provide these data in Supplementary Table 2. Rooted in behavior change to help patients reach their goals, patients learn skill building in areas like goal setting, habit formation, nutrition, and handling social situations around food. Results should be interpreted in the context of limitations of this study. Adherence to Wegovy® at time of self-reported weight is unknown. Friedrichsen et al. explore the impact of once-weekly subcutaneous semaglutide 2.4 mg on energy intake, appetite, control of eating, and gastric emptying in adults with obesity. These findings are crucial for healthcare providers considering semaglutide for patients focused on weight management. The practical implications highlight semaglutide as an effective weight management option, although cost and side effects, such as nausea and vomiting, must be considered. Among the 7,604 patients with obesity, 296 patients had reported weight values 24 months post index (±30 days).5The high cost of Wegovy raises ethical questions regarding accessibility and equity․ Its availability to all individuals who could benefit from it is a crucial consideration․ Further research is needed to explore its long-term effects and potential risks to ensure its responsible and ethical use․The scale was calibrated yearly as a minimum unless the manufacturer certified that calibration of the weight scales was valid for the lifetime of the scale.A lower energy intake was considered the key factor responsible for bodyweight reduction.8 The Semaglutide Treatment Effect in People with Obesity (STEP) program is a phase III clinical trial program focused on the approval of semaglutide as a weight loss medication in patients with obesity.To capture the effects of semaglutide across diverse ethnic backgrounds, the review will include studies with participants from various ethnic groups.Currently, the FDA has only given approval to Wegovy, 2.4 mg, subcutaneous semaglutide, as an antiobesity medication.7 In the future, it may be beneficial to explore oral semaglutide as a weight loss medication, given limited efficacy differences between oral and subcutaneous semaglutide and possible preference toward an oral agent in patient populations.The study used paracetamol absorption after a standardized breakfast to assess gastric emptying but did not directly measure gastric emptying with semaglutide. Currently, the FDA has only given approval to Wegovy, 2.4 mg, subcutaneous semaglutide, as an antiobesity medication.7 In the future, it may be beneficial to explore oral semaglutide as a weight loss medication, given limited efficacy differences between oral and subcutaneous semaglutide and possible preference toward an oral agent in patient populations. In a recent study, most patients reported preferring taking oral tablets to subcutaneous injections, supported by the ease of administration and the lack of pain.40 From these results, most patients would possibly prefer to take an oral tablet of semaglutide than a once-weekly subcutaneous injection. The STEP program did compare 1.0 mg subcutaneous semaglutide and 2.4 mg subcutaneous semaglutide, finding that weight reduction is improved with a dose increase.12 Continuous endpoints were analyzed using an analysis of covariance model with treatment as a fixed factor and baseline value of the endpoint as a covariate. Body weight was measured without shoes and only wearing light clothing; it was measured on a digital scale and recorded in kilograms or pounds (one decimal with a precision of 0.1 kg or lb), with preference for using the same scale throughout the trial. The lifestyle counseling was not targeted at weight loss. Clinically meaningful weight loss was evident in the semaglutide group within a broad range of baseline categories for glycemia and body anthropometrics. The BMI category change reflects the superior weight loss with semaglutide, which resulted in fewer patients being in the higher BMI categories after 104 weeks. At week 104, 52.4% of patients treated with semaglutide achieved improvement in BMI category compared with 15.7% of those receiving placebo. At week 208, average reduction in WC was −7.7 cm with semaglutide versus −1.3 cm with placebo, with a treatment difference of −6.4 cm (95% CI −7.18 to −5.61; P 21. Each patient’s percentage change in body weight is plotted as a single bar.Full size imageWC change from baseline to 104 weeks has been reported previously in the primary outcome paper21. Data availability The trial protocol was designed by the trial sponsor, Novo Nordisk, and the academic Steering Committee.Originally developed for the treatment of type 2 diabetes, semaglutide has also been investigated for its potential use in individuals with obesity or overweight without diabetes .Studies have also investigated the gastrointestinal (GI) side effects, namely nausea and vomiting, reported by trial participants and whether or not these have contributed to the weight loss effects of GLP-1 RAs in any manner.The proportions of individuals with BMI −2 who achieved sex- and race-specific cutoff points for WC (indicating increased metabolic risk) were evaluated at week 104.“Wegovy and Ozempic both contain semaglutide as their active ingredient; however, they have different FDA-approved indications,” she explains.ETD, estimated treatment difference; HbA1c, glycated hemoglobin; MI, myocardial infarction; PAD, peripheral artery disease; sema, semaglutide.Vs 2.3% of patients with placeboThe study concluded that semaglutide 2.4 mg can lead to significant weight loss and improve cardiometabolic risk factors, underscoring its effectiveness in weight management . The recommended dosages are based on the data from clinical trials for that specific use.” Based on known dose schedules and clinical data, the calculator charts your expected progress week by week and shows when you'll reach your goal. Wegovy should only be used under the guidance of a healthcare professional․ Regular monitoring is necessary to assess its efficacy, manage side effects, and adjust dosage as needed․ This highlights the importance of open communication between patients and their doctors to ensure safe and effective weight loss․ Mark, already physically active, initially sees faster weight loss than Sarah․ His demanding work contributes to his metabolism, but he also experiences more pronounced side effects like constipation and fatigue, particularly during the initial weeks․ He needs to adjust his workout routine to accommodate the side effects and ensure he’s adequately hydrated․ By week 6, Mark achieves substantial weight loss, showcasing how individual metabolic responses and lifestyle factors interact with Wegovy's effects․ His experience demonstrates the need for individualized medical monitoring to manage side effects effectively․ This literature review summarizes findings from the SUSTAIN, PIONEER, and STEP clinical trial programs, which tested both injected and oral forms of semaglutide . The main limitation of this study is that it focuses solely on the efficacy of semaglutide and does not compare it to other treatment options. O'Neil et al. evaluate the effects of semaglutide 2.4 mg on health-related quality of life, control of eating, and body composition. Based on the Semaglutide Treatment Effect in People with Obesity (STEP) program, Ghusn et al. demonstrate significant and sustained weight loss with semaglutide, along with improved cardiometabolic factors. Of note, in the lower BMI categories (−2 (overweight) and 30 to −2 (class I obesity)), the proportion of Asian individuals was higher (14.5% and 7.4%, respectively) compared with the proportion of Asian individuals in the higher BMI categories (BMI 35 to −2 (class II obesity; 3.8%) and ≥40 kg m−2 (class III obesity; 2.2%), respectively). In patients with type 2 diabetes and high CV risk, semaglutide at doses of 0.5 mg and 1.0 mg has been shown to significantly lower the risk of CV events20. Remediating the adverse health effects of excess abnormal body fat through weight loss is a priority in addressing the global chronic disease burden. These data are from the cumulative frequency distribution for change in body weight.9 The majority of patients taking Wegovy® achieved clinically meaningful weight loss The study reviewed a limited number of clinical trials (12 papers), with limitations in sample size and follow-up duration.If your next dose is less than 2 days away, skip the missed dose and just take your next dose on your regularly scheduled day.They advise against taking two doses at the same time to make up for a missed one.Trial data and other pertinent articles were obtained via database search through the US National Library of Medicine Clinical Trials and the National Center for Biotechnology Information.Studies focusing on pediatric or adolescent populations (under 18 years) will be excluded, as the physiological and psychological factors influencing weight management can differ significantly between children and adults.SELECT also did not include individuals who have excess abnormal body fat but a BMI −2.The semaglutide dosage schedule is a carefully designed ramp-up intended to make the treatment as safe and comfortable as possible.Our free GLP-1 weight loss calculator helps you project your weight loss journey using medications like Ozempic, Wegovy, and Mounjaro.Semaglutide not only showed improvement in diabetes and body weight but also lowered the rate of cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke in patients with diabetes mellitus type 2 at high risk of cardiovascular disease.16 In her books and articles, Rita offers practical tips and insights on how to care for your body, mind, and spirit to achieve optimal health and wellness. Rita Faycurry, RD is a board-certified Registered Dietitian Nutritionist specializing in clinical nutrition for chronic conditions. She combines her comprehensive knowledge with a dedication to patient-centered care, embodying a commitment to enhancing healthcare standards in her field. Chandana Balasubramanian is a science writer who loves to translate complex science into clear insights on metabolism, weight management, nutrition, and much more. Weight plateaus are normal as your body adapts, and factors like poor sleep, stress, or lack of physical activity can interfere with results even on medication. Cut through the complexity with these clear, doctor-recommended charts for maximum weight loss results. Starting semaglutide can feel overwhelming when you're facing questions about dosing, side effects, and realistic expectations. In addition, this medication is supposed to be used for long-term weight management, which can add high costs to the management of obesity, a growing pandemic. Another significant benefit of semaglutide is that it can be used for long-term management of weight. A future study comparing these two agents would be a beneficial addition to the literature on the efficacy of semaglutide. GLP-1 Medication Comparison Meier discusses the efficacy of semaglutide, the only GLP-1 RA available in both injectable and oral formulations. Semaglutide is approved for chronic weight management in adults and is the first drug approved for this purpose since 2014. This approach ensures the inclusion of diverse and relevant studies, enabling a thorough evaluation of semaglutide's effectiveness, safety, and broader health impacts. Studies limited to a specific ethnic group without examining the broader implications will be excluded, as they may not provide a comprehensive view of semaglutide's effectiveness across different populations. Studies focusing on pediatric or adolescent populations (under 18 years) will be excluded, as the physiological and psychological factors influencing weight management can differ significantly between children and adults. These waterfall plots show the variation in weight-loss response that occurs with semaglutide and placebo and show that weight loss is more prominent with semaglutide than placebo. Within each obesity class (−2, 30 to −2, 35 to −2, and ≥40 kg m−2), there were fewer SAEs in the group receiving semaglutide compared with placebo. These waterfall plots show the variation in weight-loss response that occurs with semaglutide and placebo and show that weight loss is more prominent with semaglutide than placebo.Fig. And while doctors almost always opt for the recommended starting dose, sometimes doctors will stray from the guidelines after the first dose. “Wegovy and Ozempic both contain semaglutide as their active ingredient; however, they have different FDA-approved indications,” she explains. HaVy Ngo-Hamilton, Pharm.D., who is a pharmacist and clinical consultant at BuzzRx, tells Woman’s World you should always plan to adhere to FDA guidelines, unless told otherwise by your doctor. Wegovy and Ozempic are both semaglutide medications, while Mounjaro and Zepbound are both tirzepatide medications. Human participants research Diversity of study population - the review highlighted the inclusion of diverse populations across studies, with variations in age, sex, and ethnicity. Patient-centered outcomes - studies included in the review also assessed patient-centered outcomes, such as quality of life and treatment satisfaction. The incidence of serious adverse events was low, and semaglutide was well-tolerated by the majority of participants. All patients received instruction for a reduced-calorie diet (~500 kcal/day deficit) and increased physical activity counseling (recommended to a minimum of 150 min/week) through the trial.The BMI category change reflects the superior weight loss with semaglutide, which resulted in fewer patients being in the higher BMI categories after 104 weeks.Comparing the results presented in both trials, we observe that in the primary placebo-controlled trial from the PIONEER program and SUSTAIN 1, around 40% of participants on semaglutide achieved a weight loss of 5% or more.21 31 Thus, these results could suggest that semaglutide is outperformed by phentermine-topiramate and liraglutide as antiobesity medications.These doses are bioequivalent to 1.5 mg, 4 mg, and 9 mg, which are the commercially available, FDA-approved doses.Subgroup analyses will examine the efficacy and safety of semaglutide across different demographic or clinical subgroups, including age, sex, baseline BMI, race or ethnicity, and the presence of obesity-related comorbidities.Deng et al. further supported these findings, noting that semaglutide therapy resulted in a clinically relevant weight loss of 48.2% to 88.7% .The review will include studies examining the effects of semaglutide on weight loss in individuals without diabetes.A range of studies have demonstrated the efficacy of semaglutide in promoting weight loss in adults with overweight or obesity. All three clinical trials demonstrated that semaglutide (injected or oral) has superior efficacy compared with placebo and other antidiabetic medications in weight reduction, which led to Food and Drug Administration approval of Wegovy (semaglutide) for weight loss. In conclusion, this analysis of the SELECT study supports the broad use of once-weekly subcutaneous semaglutide 2.4 mg as an aid to CV event reduction in individuals with overweight or obesity without diabetes but with preexisting CVD. Among in-trial (intention-to-treat principle) patients at week 104, weight loss of ≥5%, ≥10%, ≥15%, ≥20% and ≥25% was achieved by 67.8%, 44.2%, 22.9%, 11.0% and 4.9%, respectively, of those treated with semaglutide compared with 21.3%, 6.9%, 1.7%, 0.6% and 0.1% of those receiving placebo (Fig. 2a). B,c, Percentage change in body weight for individual patients from baseline to week 104 for semaglutide (b) and placebo (c). Aisha's journey is characterized by the challenges of integrating Wegovy into a demanding academic schedule․ She finds it difficult to maintain a consistent diet and exercise routine due to irregular study hours․ While she experiences appetite suppression, consistent weight loss is slower than Mark's․ She emphasizes the importance of mental well-being in the weight loss journey, highlighting the need to prioritize self-care amidst academic pressures․ Aisha's experience underscores the holistic nature of weight management, incorporating mental and emotional factors alongside physical changes․ This article explores the potential of Wegovy for weight loss over a six-week period, examining the process from individual experiences to broader societal implications․ We will analyze the transformation through various lenses, acknowledging the complexities and nuances involved, avoiding simplistic narratives and acknowledging diverse perspectives․ However, the most significant weight loss typically occurs as you reach the higher, more effective doses. Whether you’re prescribed Wegovy for weight loss or Ozempic for type 2 diabetes, the process starts low and goes slow for a reason. We observed that Asian patients were less likely to be in the higher BMI categories of SELECT and that the population of those with BMI −2 had a higher percentage of Asian race. SELECT also did not include individuals who have excess abnormal body fat but a BMI −2. In SELECT, investigators were allowed to slow, decrease or pause treatment. Third, major differences existed between the respective trial protocols. Several reasons may explain the observation that the mean treatment difference was −12.5% in STEP 1 and −8.7% in SELECT. “In more severe cases, the doctor may suggest they reduce their dose temporarily before reattempting an increase.” Patients generally want to meet their “goal dose” quickly, to see the most progress. “We prescribe patient’s scheduled doses, increasing incrementally, so their bodies can adjust gradually.” They may increase weekly or decrease, depending on if you’re just getting started, or weaning off it. Dosage charts show patients the trajectory of their progress. Weight loss in pounds (lb) calculated as 5%, 10%, 15%, and 20% of mean baseline body weight of Wegovy® and placebo patients. During the trial, 13% of patients in the Wegovy® arm discontinued treatment compared with 27% in the placebo arm.1Missing data were imputed from retrieved subjects of the same randomized treatment arm (RD-MI). Wilding et al. demonstrate the effectiveness of once-weekly semaglutide at a dose of 24 mg in achieving significant weight loss in adults with obesity. Rajagopal et al. discuss the effects of semaglutide on weight loss and gastrointestinal disorders in overweight or obese adults without diabetes . Additionally, Deng et al. conducted a systematic review of the effects of semaglutide and liraglutide on individuals with obesity or overweight without diabetes. The review will explore predictors of response to semaglutide treatment, such as baseline characteristics (age, sex, BMI, metabolic parameters, and genetic factors), to identify factors that may influence treatment outcomes. Semaglutide represents a valuable addition to the therapeutic options available for individuals struggling with obesity or overweight. Sustainability of weight loss - evidence suggested that weight loss achieved with semaglutide was sustainable over time, with many studies reporting continued weight maintenance during follow-up periods. The results indicated that both subcutaneous and oral formulations of semaglutide were effective in promoting weight loss, with subcutaneous administration often yielding greater results. To assess the comparative effectiveness of semaglutide, studies comparing it to a placebo, other pharmacological weight loss treatments, behavioral interventions, or surgical interventions will be included.The analysis did reveal that tolerability may differ among specific BMI classes, since more discontinuations occurred with semaglutide among lower BMI classes.Click to see full study design below.The trial product estimand data here measure the hypothetical change in body weight of patients on Wegovy® if all participants remained on randomized treatment without discontinuation or use of rescue intervention (ie, any other obesity medication or bariatric surgery).The paper highlights that while both forms are effective, differences in inclusion criteria, trial duration, and analysis approaches across trials mean the HbA1c reductions cannot be directly compared.The systematic review of studies evaluating the effects of semaglutide in individuals with obesity or overweight without diabetes revealed several key findings regarding its efficacy, safety, and impact on patient-centered outcomes.Participants were recruited based on BMI, excluding those with a diagnosis of type 2 diabetes,11 13–15 except STEP 2, which did not exclude patients with type 2 diabetes.12 The experimental dose given during the trial was 2.4 mg, delivered subcutaneously once a week. With the recent approval of Wegovy, we could expect improvement in patients’ weight loss-related outcomes and quality of life. The only apparent difference between oral semaglutide and subcutaneous semaglutide, besides slight differences in their efficacy in weight reduction, is the route of administration. In East Asians, beta cell dysfunction is the primary factor causing type 2 diabetes, while insulin resistance and body fat play a minor role compared with Caucasians. Zhang found that a weekly dosage of 2.0 mg or higher was most effective, particularly in those with severe obesity . This is a growing problem, with Wang et al. predicting a rise to 2.3 billion overweight and 700 million obese individuals by 2015 7,8. Even though you may be taking semaglutide, the brand varies by dose. That said, Dr. Ngo-Hamilton explains it’s important to stay on the current dose for at least four weeks to build tolerance. In the semaglutide group, 12.0% of patients achieved a BMI −2, which is considered the healthy BMI category, compared with 1.2% for placebo; per study inclusion criteria, no patients were in this category at baseline. A, Categorical weight loss from baseline at week 104 for semaglutide and placebo. For those in the semaglutide group, the weight-loss trajectory continued to week 65 and then was sustained for the study period through week 208 (−10.2% for the semaglutide group, −1.5% for the placebo group; treatment difference −8.7%; 95% CI −9.42 to −7.88; P 35 days). The SELECT trial (Semaglutide Effects on Heart Disease and Stroke in Patients with Overweight or Obesity) studied patients with established CVD and overweight or obesity but without diabetes. Once-weekly subcutaneous semaglutide 2.4 mg, a glucagon-like peptide-1 receptor agonist, is approved for chronic weight management14,15,16 and at doses of up to 2.0 mg is approved for type 2 diabetes treatment17,18,19. They advise against taking two doses at the same time to make up for a missed one. If your next dose is less than 2 days away, skip the missed dose and just take your next dose on your regularly scheduled day. According to the manufacturer's guidance, if you miss a dose of Wegovy and your next scheduled dose is more than 2 days (48 hours) away, you should take the missed dose as soon as possible. The titration schedule is a critical safety measure, and the 0.25 mg dose is intended to be the starter dose.” In SELECT, at 208 weeks, semaglutide produced clinically significant weight loss and improvements in anthropometric measurements versus placebo.“We prescribe patient’s scheduled doses, increasing incrementally, so their bodies can adjust gradually.”The first STEP trial did include lifestyle modifications as part of their experimental requirements and found that 86.5% of participants on semaglutide achieved a weight loss of at least 5%.11 Therefore, it is reasonable to assume that semaglutide, combined with other interventions, would meet or exceed the accomplishments of liraglutide or even phentermine-topiramate.The study reported substantial, sustained weight loss and a higher percentage of participants achieving ≥5% weight loss with semaglutide.Starting semaglutide can feel overwhelming when you're facing questions about dosing, side effects, and realistic expectations.The favorable safety profile, characterized by predominantly mild to moderate adverse events, further supports its use in clinical practice.The study discusses the potential of semaglutide, noting that while it is effective for weight loss, the inclusion of lifestyle changes is crucial for addressing overweight and obesity comprehensively. Goldenberg and Bradley both emphasized the potential of semaglutide in reducing weight and improving cardiometabolic risk factors, with Bradley specifically noting the medication's favorable effects on these factors 16,17. This was supported by Aroda, who highlighted the consistent superiority of semaglutide in glycemic control and weight loss . While semaglutide can be an effective tool for weight management, it is most successful when used as part of a comprehensive treatment approach that includes lifestyle modifications such as diet and exercise (D&E) . In a retrospective, observational study of US adults with obesity, 83.3% Wegovy® patients vs 34.9% of placebo patients 0.8 bpm reduction with placebo Furthermore, the cardiometabolic benefits of weight loss are driven by reduction in the abnormal ectopic and visceral depots of fat, not by reduction of subcutaneous fat stores in the hips and thighs. This plateau has been termed the ‘set point’ or ‘settling point’, a body weight that is in harmony with the genetic and environmental determinants of body weight and adiposity31. There is a plateau of weight that occurs after weight loss with all treatments for weight management. The proportion (percentage) of weight loss seems to be less, on average, in the BMI −2 category relative to higher BMI categories, despite their receiving of the same treatment and even potentially higher exposure to the drug for weight loss30. She's looking for the weight-loss efficacy of a GLP-1 in pill form The 25 mg dose was studied in OASIS 4 and is available as the maintenance dose. These doses are bioequivalent to 1.5 mg, 4 mg, and 9 mg, which are the commercially available, FDA-approved doses. In OASIS 4, the doses used in escalation were 3 mg, 7 mg, and 14 mg. Semaglutide weight loss dosage chart (Wegovy) To our knowledge, no previous studies have compared the differences in the efficacy of oral and subcutaneously injectable semaglutide, which should be addressed in future research. Around 60%–93% of the population were white in SUSTAIN 1–10, STEP, and PIONEER 1–8 trials, and about 2%–10% were black or Asian. SUSTAIN 1–10, PIONEER and STEP trials are multicenter, multinational, randomized controlled trials, except PIONEER 9 and 10, conducted in Japan. This would be a fruitful avenue for future research on pharmacotherapeutics for weight reduction. The trial program was completed in March 2021 with a total of five trials; however, the results are still pending for STEP 5 (table 5). Presently, most animal and human studies exploring these mechanisms have been conducted using liraglutide.1 3 With the approval of Wegovy, further studies could be conducted focusing on the mechanisms of GLP-1 RAs in weight loss and studies on combinatorial pharmacotherapeutics in weight loss. Along with increased patient satisfaction, the approval of Wegovy as a weight loss medication could result in more avenues to investigate the many underlying mechanisms of weight loss by GLP-1 RAs. This could provide an option with higher prospects of regimen compliance for patients with obesity. These modifications have resulted in an increased half-life of the molecule, allowing subcutaneous semaglutide to be administered once weekly.10 Three of the 13 total trials comprising the SUSTAIN program were not included in this review due to redundancy of the medications’ comparisons.17–19 The most recent literature search was performed in July 2021. In fact, in most SUSTAIN trials, patients on semaglutide reported better overall treatment satisfaction over comparators.27 Crucial to the present argument regarding semaglutide’s place as a weight loss medication, the SUSTAIN 10 trial showed that semaglutide also held superiority over liraglutide, which is currently marketed for weight loss as Saxenda, in overall weight loss, the number of participants achieving weight loss of ≥5%, and the number of participants achieving weight loss of ≥10% (table 1).23 Of note, subcutaneous semaglutide only requires once-weekly administration, whereas liraglutide is administered once daily. Semaglutide not only showed improvement in diabetes and body weight but also lowered the rate of cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke in patients with diabetes mellitus type 2 at high risk of cardiovascular disease.16 ≥20% weight loss maintained with Wegovy® by one-third of patients at 2 years1‡§ Vs 2.6% (~6 lb) weight loss with placebo While the results are promising, the study points out potential increases in side effects at higher dosages and questions the durability of appetite suppression with once-weekly dosing. Additionally, the reduction in ALT was not sustained at lower doses of semaglutide, indicating a dose-dependent effect. By activating GLP-1 receptors in the brain, semaglutide helps to decrease appetite, increase feelings of fullness, and reduce food intake, ultimately leading to weight loss . “If a patient experiences side effects, their doctor may suggest they stay on the same dose for longer to give their body more time to adjust,” Dr. Wyllie says. “This can be for several reasons, including how the patient tolerates the medication’s side effects and their clinical responses to the treatment.” The study emphasizes the importance of combining semaglutide treatment with a weight management program consisting of a reduced-calorie diet and increased physical activity. Semaglutide led to significant reductions in body weight, waist circumference, and blood pressure, along with positive changes in glycated hemoglobin and lipid levels. The study reviewed data from STEP 1-5 trials and found gastrointestinal events to be the most common adverse events, although generally mild and transient . The systematic review by Deng et al. indicates that both liraglutide and semaglutide lead to clinically relevant weight loss and are well-tolerated. They pointed out the limitations of lifestyle interventions and drug therapies, which are often disappointing in achieving significant weight loss compared to semaglutide . Patients in STEP 1 were desirous of weight loss as a reason for study participation and received structured lifestyle intervention (which included a −500 kcal per day diet with 150 min per week of physical activity). Furthermore, both sexes, all races, all body sizes and those from all geographic regions were able to achieve clinically meaningful weight loss. The proportion of patients with obesity (BMI ≥30 kg m−2) fell from 71.0% to 43.3% in the semaglutide group versus 71.9% to 67.9% in the placebo group. 4, which depicts in-trial patients receiving semaglutide and placebo. At week 104, 41.2% fell below the sex- and race-specific cutoff points for the semaglutide group, compared with only 18.0% for the placebo group (Fig. 3). Change from baseline in body weight by week for A, All participants in…The treatment policy estimand data above (15.2% mean weight loss with Wegovy® pen vs 2.6% with placebo at 2 years) measure the change in body weight among all randomly assigned participants on Wegovy®, regardless of treatment discontinuation or use of rescue intervention.These waterfall plots show the variation in weight-loss response that occurs with semaglutide and placebo and show that weight loss is more prominent with semaglutide than placebo.The review also addresses methodological considerations, including study design, participant selection, and outcome measures, to assess the robustness of the evidence.Furthermore, the data allow examination of changes in anthropometric measures such as BMI, waist circumference (WC) and waist-to-height ratio (WHtR) as surrogates for body fat amount and location22,23.While specific limitations are not detailed in the summary, the study supports the overall effectiveness of semaglutide in various forms for weight reduction. That way, Dr. Wyllie says, the body can adjust to either the semaglutide or tirzepatide injection. “For example, on Wegovy, a patient will start on 0.25 mg once weekly, stay on that dose for four weeks and then progress to 0.5 mg,” Dr. Crystal Wyllie of Zava Online Doctor explains. “Ozempic is approved to treat type 2 diabetes, while Wegovy is approved for chronic weight management. The study underscored semaglutide's effectiveness in promoting significant, sustained weight loss over an extended period . The study reported substantial, sustained weight loss and a higher percentage of participants achieving ≥5% weight loss with semaglutide. The study concluded that semaglutide 2.4 mg can lead to significant weight loss and improve cardiometabolic risk factors, underscoring its effectiveness in weight management . The study reviewed a limited number of clinical trials (12 papers), with limitations in sample size and follow-up duration. However, the "best" dose is ultimately the highest dose you can comfortably tolerate while still achieving your health goals, as determined by you and your doctor. It's also about creating routines and habits that support your treatment. The "best" dose is the one that is both effective and tolerable for you long-term. Please consult your healthcare provider or visit the Wegovy side effects or Ozempic side effects web pages. Consult a healthcare provider before making any adjustments to your prescribed dose or schedule.” The review also discusses the cardiovascular benefits suggested by the trials, although the completion of the SOUL trial is waiting for definitive conclusions. The review discusses the potential benefits and implications of semaglutide for these conditions but notes limitations such as small sample sizes and a lack of long-term follow-up data. Simranjit reviews the literature on semaglutide's application in treating obesity and non-alcoholic fatty liver disease (NAFLD) . The key factors influencing cost-effectiveness included treatment duration, subsequent therapy, and weight-rebound rates, highlighting the model parameters' significant impact on the cost-effectiveness probability. The systematic review of studies evaluating the effects of semaglutide in individuals with obesity or overweight without diabetes revealed several key findings regarding its efficacy, safety, and impact on patient-centered outcomes. RCTs are studying the use of semaglutide (both subcutaneous and oral formulations) for weight management in individuals with obesity or overweight without diabetes. Xie et al. supported the efficacy of semaglutide in promoting weight loss in individuals with obesity or overweight without diabetes, noting that while semaglutide 2.4 mg was the most effective for loss . These studies also highlighted the safety of semaglutide, with O'Neil et al. noting that it was generally well tolerated and led to clinically relevant weight loss compared to placebo . It found that semaglutide treatment improves weight-related quality of life significantly more than placebo, along with improvements in control of eating and body composition. The practical implications of their findings suggest that both liraglutide and semaglutide could be effective options for weight loss in obese or overweight individuals without diabetes. Their analysis of phase III clinical trial results demonstrated that semaglutide provides clinically meaningful and sustained weight loss, which exceeds the outcomes achieved with previously available pharmacotherapies. This analysis highlights the importance of combining semaglutide treatment with lifestyle interventions for optimal results, recommending a target dose of 2.0 mg or more once weekly for effective weight management. To assess the comparative effectiveness of semaglutide, studies comparing it to a placebo, other pharmacological weight loss treatments, behavioral interventions, or surgical interventions will be included.