We anticipated that the results of the analysis would help to determine the mechanisms of weight loss observed with semaglutide and other GLP‐1RA therapies and, in particular, whether nausea and vomiting are directly involved. The relationship between nausea‐ or vomiting‐related events and semaglutide‐induced weight loss was assessed in a mediation analysis. The safety findings were similar to those reported with semaglutide in the individual SUSTAIN 1 to 5 trials.15, 16, 17, 18, 19 In general, the GI disorder AE rate was higher with semaglutide than with comparators, with more GI AEs occurring in the lower versus higher baseline BMI subgroups. Adverse events by baseline BMI (pooled data from SUSTAIN 1 to 5 trials) Rates of premature treatment discontinuation with semaglutide were also higher in subjects with lower baseline BMI compared with those with a higher baseline BMI (Table 2). Age, pre-existing medical conditions, economic status, drug tolerance, and drug interactions will differ greatly between patients. Obesity treatment and management is multi-factorial and should ideally be tailored to be personalized for each individual. Similarly, in this study, the most common AEs were also GI symptoms and were transient in duration. In STEP 8, semaglutide and liraglutide had a discontinuation rate of 3.2% and 12.6%, respectively . Resistin plays a regulatory role in insulin resistance and is reported to possibly play an important link between obesity and the development of T2DM . 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 . Strathe et al. developed a model-based approach to predict individual weight loss with semaglutide in people with overweight or obese. The authors conducted a comprehensive systematic review and meta-analysis by searching multiple databases to include RCTs evaluating semaglutide's efficacy and safety in this population. Things like age, kidney health, and other health problems can change how the body responds to the medicine. Your healthcare provider will support you in handling any side effects you may experience. It is very important to know the signs and symptoms of possible side effects and the potential risk of serious conditions. They may recommend adjusting your dosage or exploring other treatment options. All subjects were informed of the study’s aims and provided written consent before they were enrolled in the study. It reduces liver glucose production, enhances insulin sensitivity in body tissues (11), decreases hyperinsulinemia by reducing insulin resistance and increases the secretion of growth/differentiation factor 15 (GDF15), which suppresses appetite and reduces caloric intake (13–16). In addition, it has demonstrated effectiveness in prediabetes and in insulin-resistant conditions, including polycystic ovary syndrome (PCOS) (11, 12). 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. This was also observed in Look AHEAD, a lifestyle intervention study for weight loss30. Furthermore, as BMI exceeds 30 kg m−2, weight loss amounts are more similar for class I, II and III obesity. An interesting observation from this SELECT weight loss data is that when BMI is ≤30 kg m−2, weight loss on a percentage basis is less than that observed across higher classes of BMI severity. Independently of results on body weight, and in patients who did not obtain a 5% decrease in their body weight, insulin basal values decreased, and HOMA-IR improved. Almost 80% of the studied obese PCOS patients obtained at least a 5% decrease in their body weight. In this study, we present the data on the use of semaglutide, an incretin mimetic drug, in obese PCOS patients who were unresponsive to a lifestyle modification program. In fact, our results demonstrated the effectiveness and safety over 24 months of semaglutide treatment in T2DM obese subjects on loss of weight and HBA1C improvement. This allowed us to report data only at 12 months for oral semaglutide from baseline. Meta-analysis results of WC change (cm) in included trials.Meta-analysis results of RBW change (%) in included trials.As a result, it improves glycemic control and reduces the risk of issues connected to diabetes.Meta-analysis results of SBP change…First, the latest and most comprehensive systematic review examining the weight loss effects of semaglutide was totally conducted in obese or overweight patients without diabetes, which is expected to provide favorable strategies for normal obese patients as a conventional weight-lowering drug.The other three studies did not directly explore the weight loss effect in obese or overweight patients without diabetes, but demonstrated it in other ways, such as reducing appetite and energy intake, delaying gastric emptying, and decreasing local fat accumulation, respectively (Hjerpsted et al., 2018; Friedrichsen et al., 2021; Jensterle et al., 2021). Other successes, such as decreasing waist circumference and BMI of patients, were also observed. These modifications have resulted in an increased half-life of the molecule, allowing subcutaneous semaglutide to be administered once weekly.10 All pertinent journal entries used to create this review were obtained via search with the National Center for Biotechnology Information database. 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. Semaglutide’s current high cost limits its cost-effectiveness for use in adolescents with obesity, and varying insurance coverage may contribute to inequities in uptake, exacerbating socioeconomic disparities in pediatric obesity. Semaglutide treatment for children with obesity: an observational study However, the principal strength of this study was the long-term observation, providing the first insights into a potential novel strategy for partially overcoming adaptive mechanisms following the cessation of semaglutide-induced weight loss in insulin-resistant populations. This analysis demonstrated that GI side effects occurred in 37.6% of participants receiving semaglutide plus metformin, compared to 40.3% of those receiving semaglutide alone. The observations are in line with a post hoc analysis of gastrointestinal (GI) adverse effects in participants who received concomitant metformin with semaglutide 1mg per week in the SUSTAIN 6 study. The cardiometabolic improvements seen during semaglutide treatment reverted towards the baseline in our study, similar to the findings in the STEP 1 study (10). When using semaglutide injections for weight loss, it is generally recommended to continue the treatment for an extended period, as maintaining weight loss can be challenging. The magnitude of weight loss achieved with semaglutide was unprecedented among pharmacologic interventions for obesity, making it a game-changer in the field of obesity management. For people taking semaglutide for weight loss, the recommended duration of treatment can vary depending on several factors, including the individual's health status, weight-loss goals, and response to the medication. Learn how quickly weight loss happens with Farxiga, what clinical trials show, typical results, and how it compares to other medical weight-loss options. In the first four weeks, many users experience noticeable body weight loss (typically 5-10 pounds), along with improved appetite control. In a study discussing the risks and rewards of semaglutide for obesity treatment, Winter emphasized semaglutide's effectiveness for weight loss in overweight and obese non-diabetic adults. 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 review will include studies examining the effects of semaglutide on weight loss in individuals without diabetes. Efficacy in weight loss - participants receiving semaglutide demonstrated significant weight loss compared to those on placebo or other anti-obesity medications. 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. We suspect this may be the case and suggest further studies to explore this aspect of weight-loss physiology. The phenotype of cardiometabolic disease but lower BMI (−2) may be one where reduction of excess abnormal and dysfunctional body fat does not require as much body mass reduction to achieve health improvement. Future studies should evaluate CV risk reduction in Asian individuals with high CV risk and BMI −2. 4.2 BMI and WC changes Studies focusing exclusively on one sex without a comparative analysis will be excluded to avoid gender bias. 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. The systematic review will focus on studies involving adults aged 18 years and older to ensure the findings apply to the adult population. The incidence of serious adverse events was low, and semaglutide was well-tolerated by the majority of participants. Commonly reported side effects included gastrointestinal symptoms such as nausea, vomiting, and diarrhea. 8Psychiatric weight-related conditions included depression, generalized anxiety disorder, and bipolar disorder or schizophrenia Other common comorbidities were MAFLD, reproductive abnormalities, psychiatric disorders, and obstructive sleep apnea, with 32 out of 40 individuals (80%) having two or more weight-related medical conditions. In total, 17 out of 40 patients (42.5%) combined the presence of at least three criteria, which constituted the diagnosis of metabolic syndrome according to the National Cholesterol Education Program (NCEP) Adult Treatment Plan III (ATP III) definition . All patients were of White Greek ethnic origin, mostly females (28/40 or 70%), with a median age of 47, ranging from 23 to 65 years old. Out of 40 patients, five individuals had undergone bariatric surgery in the past, including gastric banding in four cases and sleeve gastrectomy in one case. Christou et al. evaluate the weight loss efficacy and safety of semaglutide as an antiobesity drug, meeting the criteria set by both the EMA and FDA. Newsome et al. explore the effects of semaglutide on liver enzymes (ALT) and markers of inflammation (hsCRP) in subjects with type 2 diabetes and/or obesity. Rosenberg (2021) reports in his study on the effectiveness of once-weekly subcutaneous semaglutide administration combined with lifestyle interventions in achieving sustained, clinically relevant weight loss in obese or overweight adults. Ojeniran et al. report on the effectiveness of semaglutide 2.4 mg weekly for weight loss, highlighting significant results from a weight loss study . Semaglutide in HFpEF across obesity class and by body weight reduction: a prespecified analysis of the STEP-HFpEF trial A total of 1023 patients had semaglutide prescription for obesity. We included patients with a body-mass index (BMI) ≥ 27 kg/m2 who were prescribed weekly semaglutide subcutaneous injections. Moreover, it achieved a higher proportion of patients who experienced weight loss exceeding 5%, 10%, 15% and 20%. Through a review of the literature, data were extracted from relevant studies and assessed for quality, and a meta-analysis was conducted using RevMan 5.4.1 software. The best results are obtained in patients with mild obesity, while patients with severe obesity are generally unresponsive to the product, at least at the used doses. Additional research is needed to assess trends in utilization and adherence to minimize the risk of worsening socioeconomic disparities in pediatric obesity. Thus, long-term data on the safety in adolescents is limited, particularly regarding the risks of cholelithiasis, pancreatitis, suicidal ideation, and disordered eating. Itsefficacy and safety have been demonstrated for up to 2 years, making it an idealoption for chronic weight management, although its use may be limited by itscost. Despite this, one barrier to its use that willcontinue is its cost as it is currently among the most expensive of available agents(Table 2).Clinicians who are considering prescribing semaglutide 2.4 mg should make sure toevaluate opportunities from the manufacturer to reduce the cost. Fasting blood glucose normalized in 80% of semaglutide-treated IFG PCOS women, with the remaining few IFG PCOS patients obtaining a decrease of at least 10 mg/100 mL of their fasting blood glucose. No specific lifestyle plan was added to the pharmacologic treatment, but patients were told to maintain a normal food intake and a regular physical activity. Basal BMI, fasting glucose, insulin and HOMA-IR in PCOS patients treated by semaglutide and divided according to their response to the therapy. In Table 2, some characters of highly responsive and non-responsive PCOS patients were compared. The contribution of nausea or vomiting to this weight loss was minor. It has other candidates in its late-stage obesity pipeline, headed by CagriSema, which combines dual amylin and calcitonin receptor agonist cagrilintide with semaglutide. There was no word from Novo Nordisk on plans to file the high-dose version for approval, which clearly cuts the efficacy deficit with its main rival, although, the company said it would present the data in full at a scientific conference later this year. The STEP trial examined the effects of 2.4 mg, once-weekly, subcutaneous semaglutide on patients with obesity. The SELECT clinical trial randomized 17,604 adults with obesity and cardiovascular disease to 2.4 mg once-weekly semaglutide or placebo, with a mean follow up of approximately 40 months (22). In the STEP-Teens trial, participants treated with semaglutide experienced a significant reduction in hemoglobin A1c of 0.4%, compared to a 0.1% reduction in placebo group (13). Deng et al. further supported these findings, noting that semaglutide therapy resulted in a clinically relevant weight loss of 48.2% to 88.7% . 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) . 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 . Although our study lacked the stringent and closely controlled nature of RCTs, we report similar weight loss results within the same time period as in RCTs. Considering the scarcity of AOMs, choosing the most suitable and individualized therapy is important.6 Retrospective studies comparing high doses of semaglutide (ie, 1.7 and 2.4 mg) with other AOMs are limited. This will ultimately contribute to better informed clinical practices and improved treatment strategies for individuals with obesity or overweight without diabetes. Secondary outcomes include the dose-response relationship of semaglutide, assessing different dosages and their impact on weight loss. 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. Search terms will include variations of “semaglutide,” “obesity,” “overweight,” and “randomized controlled trial.” The year of publication is 2017-present (Figure 1). A series of systematic reviews and meta-analyses have consistently demonstrated the efficacy of semaglutide in promoting weight loss in individuals without diabetes. Current studies on semaglutide suggest it may help with more than diabetes and weight loss.Since the most common adverse events (AEs) reported in the studies with semaglutide were gastrointestinal (GI), these AEs may have contributed to the weight loss.The STEP-Teens trial found that heart rate increased by a mean of 1.2 beats per minute in the semaglutide group, while it decreased by 2.3 beats per minute in the placebo group (13).Five studies (Wilding et al., 2021; Wadden et al., 2021; Rubino et al., 2021; O'Neil et al., 2018; Jensterle et al., 2021), including 4,254 individuals, reported a change in BMI.Remember, controlling diabetes takes time and hard work, just like a marathon. Dose escalation should occur after 4 weeksto doses of 0.5 mg, 1 mg, and 1.7 mg, and the maintenance dose of 2.4 mg. GLP-1 is an incretin hormone with receptors present in several areas of the body,including pancreatic alpha and beta cells, the stomach, and the central nervoussystem. Gastrointestinal sideeffects were the most frequently reported side effects, including nausea,vomiting, constipation, and diarrhea. After three months of semaglutide administration, the median (IQR) weight loss was 7 (5.3) kg, equivalent to 6.6% (5.5%) percentage weight loss. Semaglutide for weight management was prescribed for a total of 43 patients who were overweight or obese, but the analysis included 40 individuals (28 females and 12 males) following the exclusion of three individuals owing to the lack of three-month data. The primary end point was the percentage weight loss at three and six months after semaglutide initiation. It was granted an exemption from requiring ethical approval since it was a clinical audit designed to capture the clinical outcomes of patients commenced on semaglutide within its licensed use for weight loss and all the procedures being performed were part of the routine care. The aim of this real-world retrospective study was to evaluate the effectiveness and adverse events of semaglutide therapy for weight management in individuals with obesity in day-to-day clinical practice. Institutional Review Board Statement Standardizing dosages (e.g., focusing on semaglutide 2.4 mg) and delivery methods would help address confounding factors. Therefore, the study designs make it difficult to sufficiently conclude the superiority of one drug over another. Third, two of the included studies were observational cohort studies, and three did not have a control group. Additionally, both subcutaneous and oral semaglutide were included which may be a confounding factor. The average percentage weight-loss trajectories with semaglutide and placebo over 4 years of observation are shown in Fig. 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). Therefore, the advent of semaglutide could represent a paradigm shift in obesity care, encompassing the widespread long-term use of pharmacotherapy across lifestyle interventions and employing a personalized treat-to-target approach, similar to the contemporary management of type 2 DM, in order to prevent and treat weight-related complications. Of note, a substantial proportion of individuals, administered with a lower-than-approved maintenance dose of 1 mg, achieved significant weight loss. Finally, a direct comparison of the weight loss effect between 1 mg and 2 mg maintenance doses was not possible since the titration decision was at the discretion of the treating clinicians, taking into account individual responses to lower doses and drug affordability. Marked variability in the therapeutic result of semaglutide highlights the need to identify the predictors of response and assess the efficacy of lower semaglutide doses, facilitating personalized decision-making. In the future, the availability of numerous potent AOMs could usher in an era of precision medicine with the application of personalized treatment strategies, based on predictive models, encompassing age, gender, different obesity phenotypes, coexisting complications, genotype, and predictors of response to each treatment modality . In addition, semaglutide improves numerous cardiovascular risk factors, including the reduction of blood pressure, total and LDL cholesterol, and triglycerides 7-9,21 and a significant decrease in C-reactive protein (CRP) concentration. This real-world study showed an early improvement in glycemic markers, confirming the glucose-lowering effect reported in STEP studies 7-9. In total, identifying predictors for the effectiveness of semaglutide is essential in order to optimize therapeutic benefits in the management of obesity. The authors conducted a comprehensive systematic review and meta-analysis by searching multiple databases to include RCTs evaluating semaglutide's efficacy and safety in this population.In our cohort of 175 patients, 94 (53.7%) had weight loss of at least 5% and 26 (14.9%) had weight loss of 10% or more at 3 months.All patients were of White Greek ethnic origin, mostly females (28/40 or 70%), with a median age of 47, ranging from 23 to 65 years old.Oral semaglutide outperformed GLP-1 RA comparators—dulaglutide and liraglutide—to promote weight loss during the program33–35 (table 3).In our study both therapies provide significant loss of weight allowing patients to reach the glycol-metabolic therapeutic goal in a short time.In men with type 2 diabetes, metformin therapy can reduce testosterone levels and counteract the testosterone elevation that may accompany improvements in blood glucose levels (38, 39).It is important to change your dose only after you talk with your healthcare provider.Lifestyleinterventions for all patients included counseling, a reduced-calorie diet, andincreased physical activity.We included patients who had at least a 3-month follow-up documented in the EMR with a BMI of 27 or more who were prescribed weekly semaglutide subcutaneous injections of 0.25, 0.5, 1, 1.7, and 2.4 mg with the primary goal of weight loss. This part often tells real stories from people who have succeeded with semaglutide. The time needed to see results from semaglutide can vary for each person. When you take semaglutide, there aren't strict rules about food. If you often miss doses, talk to your healthcare provider for advice on how to stay on track. Do not take two doses at once to make up for it. Additional studies evaluating the effects of semaglutide in adolescents with MASLD are needed to evaluate the efficacy in this patient population. As there were only eight participants with T2D in this trial, this data alone cannot be used to draw conclusions regarding semaglutide’s impact on glycemic control in youth-onset T2D (13). Notably, nearly 45% of participants randomized to semaglutide achieved a BMI in the normal weight or overweight category, versus 12% of participants assigned to placebo (14). The estimated mean percentage change in BMI from baseline to week 68 was −16.1% with semaglutide 2.4 mg and +0.6% with placebo (Table 1) (13). For lower BMI classes, discontinuation rates are higher in the semaglutide group but not the placebo group. ETD, estimated treatment difference; HbA1c, glycated hemoglobin; MI, myocardial infarction; PAD, peripheral artery disease; sema, semaglutide. Proportions of patients in the BMI categories at baseline and week 104 are shown in Fig. At baseline, mean WHtR was 0.66 for the study population. Involving around 5,000 participants across five phase 3 trials, the study randomized individuals to receive semaglutide 2.4 mg or a placebo. Kushner et al. detail the STEP with Obesity trials aimed at assessing semaglutide's impact on weight loss, safety, and tolerability. 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. At baseline (timepoint 1), at the end of semaglutide intervention (timepoint 2), and at the end of the study (timepoint 3), all participants underwent body weight assessment. At the end of the study, 21 out of 25 subjects had lower body weight compared to baseline. As we described before, the most commonly reported adverse effects of semaglutide during the SUSTAIN clinical trial were GI side effects, including nausea and vomiting.1 Patients taking semaglutide experienced these side effects more frequently than comparators (in the SUSTAIN, PIONEER, and STEP trials), but most episodes were transient.4 Higher nausea and vomiting rates were experienced at higher doses of semaglutide and lower baseline BMI.4 There are also concerns for increased pancreatic lipase and pancreatitis, similar to other GLP-1 RAs. Comparison of PIONEERS trials showed that Japanese patients had a more significant reduction in hemoglobin A1c than global trials (PIONEER 1–8).29 This finding suggests that diabetes mellitus type 2 in East Asian patients is more likely due to dysfunction of the beta cells than insulin resistance and obesity. 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. Premature treatment discontinuations across SUSTAIN 1, 2, 4 and 5 were comparable (12.2% to 15.3% for semaglutide 1.0 mg and 7.2% to 10.9% for comparators), while the rates in SUSTAIN 3 were numerically higher (20.3% and 21.0%, respectively). Overall, the proportions of subjects who discontinued treatment prematurely were 10.6% to 13.5% in the semaglutide 0.5 mg group, 12.2% to 20.3% in the semaglutide 1.0 mg group, and 7.2% to 21.0% across the comparator groups (Table 1). A total of 3899 (99.5%) subjects were exposed to their investigational product and 92.5% to 95.7% completed the trials (whether they were on or off the trial medication). Twenty-seven obese patients with a diagnosis of PCOS, who did not reduce their body weight by a lifestyle modification program, were included in this study and treated by semaglutide, 0.5 mg subcutaneously once a week. Real-world effectiveness of Semaglutide treatment on weight loss maintenance after weight loss in patients with obesity or overweight and diabetes. Weight loss during the treatment with semaglutide at week 52 was 16.2% compared to baseline at the dose of 0.4 mg/day, versus -2.3% for placebo. The Mayo Clinic institutional review board approved the study and waived the need for informed consent owing to its minimal-risk nature. Patients with a history of bariatric procedures, taking other antiobesity medications, and with an active malignant neoplasm were excluded. Weight loss of patients treated… How to Maintain Weight Loss with Semaglutide In conclusion, in our study, semaglutide treatment confirmed what was reported above. Furthermore, no patients were excluded from the study according to the retrospective nature of the study, however not all patients treated with IS or OS have reached 6-, 12- or 24-month follow-up considered for the statistical analysis. In obese patients, further studies should probably be conducted to verify whether the weight maintenance dosage was related to the starting BMI. In our study both therapies provide significant loss of weight allowing patients to reach the glycol-metabolic therapeutic goal in a short time. Our results demonstrated comparable effectiveness both with IS and IS treatment in T2DM adults with obesity and overweight. The research employs a cohort Markov model to compare eight of 16 semaglutide with various other treatments, including no treatment, D&E alone, and other branded AOMs . Kim et al. provide a comprehensive evaluation of the economic viability of semaglutide 2.4 mg as a long-term weight management therapy. The 20-week duration of the study limits the understanding of long-term effects, although the short-term findings are promising . The study used paracetamol absorption after a standardized breakfast to assess gastric emptying but did not directly measure gastric emptying with semaglutide. This literature review summarizes findings from the SUSTAIN, PIONEER, and STEP clinical trial programs, which tested both injected and oral forms of semaglutide . Singh et al. provide a comprehensive review of semaglutide, marketed as Wegovy, for chronic weight management. The study used the IWQOL-Lite-CT and SF-36v2 (RAND Corporation, USA) to assess quality of life, as well as other measures for eating control and body composition . Garvey et al. assessed the long-term efficacy and safety of semaglutide 2.4 mg versus placebo over 104 weeks. Practical implications suggest the need for more trials in diverse groups to determine efficacy and safety comprehensively. In type 2 diabetes studies, there has been a trend of decreased lean mass and fat-free mass, although not in a significant manner. GLP-1 RAs also demonstrate other positive changes beyond weight loss and glycemic control. In mouse models, semaglutide compared to liraglutide has been shown to affect more regions in the hypothalamus, hindbrain, and other neural pathways that were involved with appetite control, reward circuits, and energy expenditure . Four studies evaluated semaglutide versus liraglutide and one analyzed semaglutide versus a GLP-1/glucagon receptor co-agonist efinopegdutide. Additionally, across groups, semaglutide was started at a dose of 0.05 mg and increased every four weeks, depending on the cohort. 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 .But, you might have some common side effects as your body adjusts to the medication.At the first visit, mean weight m(W) was 101.8 ± 24.6 and kg 95.2 ± 15.0 kg; mBMI was 36.7 ± 8.7 kg/m2 and 34.3 ± 5.3 kg/m2 respectively for IS and OS group of subjects.The goal of this comprehensive analysis is to provide insights for clinicians and patients when selecting a GLP-1 RA, as well as to identify gaps in the current literature that can be explored further to optimize patient outcomes and quality of life.The efficacy of semaglutide 2.4 mg is being assessed across 8 trials in the STEPprogram.Semaglutide 2.4 mg safely and effectively produced clinically significant weight loss in all subgroups based on age, sex, race, glycemia, renal function and anthropometric categories. Links to NCBI Databases Second, we outlined the correlation between baseline variables and main effects, proposing the influence of dose on weight loss effects and adverse events, further providing direction for clinical individualized medication. In our meta-analysis, semaglutide showed a significant reduction in SBP and CRP and lowered the levels of lipid-related indicators in obese patients, which exhibited certainly positive effects on metabolic syndromes such as dyslipidemia, hypertension, obstructive sleep apnea, and cardiovascular disease. Semaglutide, a new once-weekly GLP-1RA, has performed a significant weight loss effect in obese or overweight patients with or without diabetes (Blundell et al., 2017; Ahrén et al., 2018; Kushner et al., 2020; Davies et al., 2021; Kadowaki et al., 2022), and exhibited favorable advantages in reducing obesity complications (Ryan et al., 2020; Kushner et al., 2021). Rubino et al. investigate the effects of continued semaglutide treatment versus placebo on weight loss maintenance in adults with overweight or obesity. The primary outcomes of interest for this systematic review include absolute and relative changes in body weight from baseline and the sustainability of weight loss following the cessation of semaglutide treatment. The magnitude of weight loss varied across studies, 13 of 16 with some reporting an average reduction of 10%-15% of body weight over a treatment period of 68 weeks. Independently of the effects on body weight, semaglutide treatment improves insulin resistance and may normalize fasting glucose in IFG PCOS patients. In conclusion, treatment with semaglutide, at low doses, significantly reduces body weight in almost 80% of obese PCOS patients who were unresponsive to a previous lifestyle plan. Semaglutide, as a once weekly subcutaneous injection for weight management, effectively reduces body mass index (BMI) while improving hyperglycemia, elevated alanine aminotransferase levels, hyperlipidemia, and quality of life in youth with obesity. Semaglutide is a GLP-1 receptor agonist recently approved by the FDA for weightmanagement at a dose of 2.4 mg once weekly in patients with a BMI of ≥30kg/m2 or ≥27 kg/m2 with more than one weight-relatedcomorbidity. It has shown consistentclinically significant weight loss across the STEP program, with limited major sideeffects or contraindications. Also, there is a possibility of recall bias because the dates of medication initiation and termination were reported by patients during patients’ visits or communications with their physicians and therefore may not be exact. These results may support the applicability of semaglutide in a less controlled environment, as previously proven in RCTs.18,19,20 Other adverse effects included dizziness, depression, bloating, dry mouth, and taste change. Nausea and vomiting were the most encountered adverse events (64 patients 36.6%), followed by diarrhea (15 patients 8.6%) and fatigue (11 patients 6.3%). Gastrointestinal symptoms were the most reported adverse effects. All authors had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Collected data as an investigator in some of the underlying trials, interpreted the data and wrote the manuscript. Proportion of subjects achieving ≥5% (A) and ≥10% (B) weight loss by baseline BMI. Only a small component (0.07 to 0.5 kg) of the total treatment difference in weight loss was explained by nausea or vomiting. With semaglutide 1.0 mg, the reported weight change was −5.6 to −8.0 kg in subjects experiencing nausea and/or vomiting versus −4.3 to −6.0 kg in those not experiencing these events. With semaglutide 0.5 mg, a weight change of −4.2 to −5.3 kg was reported in subjects experiencing nausea or vomiting versus −3.2 to −4.1 kg in those not experiencing these events. The median duration of nausea events was higher with semaglutide 0.5 and 1.0 mg (15 to 33 days) versus placebo (8 days) in SUSTAIN 5. In SUSTAIN 1, the difference in subjects achieving this weight loss response was not significant. Baseline age and BMI were similar across the five trials. Obesity is linked to a range of non-communicable diseases, including cardiovascular disease, diabetes, and cancer . 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. It was found that semaglutide works by mimicking the action of glucagon-like peptide-1 (GLP-1), a hormone that regulates appetite and food intake. The review also addresses methodological considerations, including study design, participant selection, and outcome measures, to assess the robustness of the evidence. Semaglutide, a glucagon-like peptide-1 receptor agonist, has emerged as a promising pharmacological intervention for weight management. Each article included in the study underwent title and abstract screening by two reviewers. Exclusion criteria included non-human studies, case reports, reviews, cadaveric studies, expert opinions, conferences, abstracts, and articles not in English. Patients with obesity were previously limited to a handful of Food and Drug Administration (FDA)-approved drugs (e.g., orlistat, phentermine-topiramate, bupropion-naltrexone) to manage obesity, with varying efficacy . 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. Recently, weight-management medications, particularly those comprising glucagon-like peptide-1 receptor agonists, that help people achieve greater and more sustainable weight loss have been developed13. However, weight-management medications that modify appetite can make attaining and sustaining clinically meaningful weight loss of ≥10% more likely12. Producing and sustaining durable and clinically significant weight loss with lifestyle intervention alone has been challenging11. Some people can lose weight fast in the first few weeks. The goal is to reach the maintenance dose while watching how you respond. You will inject this dose just under the skin once a week. The goal is to gradually reach the maintenance dose. During these visits, your provider can change your dose if necessary and answer any questions you might have. A comprehensive search will be conducted in electronic databases (e.g., PubMed, Embase, Cochrane Library) for relevant RCTs published up to the present date.B,c, Percentage change in body weight for individual patients from baseline to week 104 for semaglutide (b) and placebo (c).Apart from weight loss, other benefits include improved menstrual regularity, decreased androgen levels, and reduced symptoms of insulin resistance.In early 2024, the FDA released a drug safety communication stating that, based on detailed reviews of reports in FAERS, clinical trials, and analysis of postmarketing data using health insurance claims and patient health records, their preliminary evaluation did not find evidence that GLP-1 RA use causes suicidal thoughts or actions (31).Moreover, some of the abstracted weights were self-reported, which might be not as accurate as clinic measurements (noncalibrated vs calibrated scales).Researchers are also examining the long-term effects and safety of these new treatments. Subgroup analysis revealed semaglutide 1.0, 2.4, and 2.8 mg led to distinct reduction in body weight, BMI, and WC, but exhibited more events in semaglutide 2.8 mg, whereas less in 2.4 mg. Our systematic review of eight studies indicated that semaglutide showed an attractive weight loss effect in obese or overweight patients without diabetes. Vosoughi et al. (2021) and He et al. (2022) both explored the weight loss effect of once-weekly semaglutide for obesity, involving patients with or without diabetes. For lasting weight loss, it’s best to follow a longer-term plan under medical supervision to gradually adjust dosage and maintain results. Some users transition to a maintenance dose to keep their appetite controlled and prevent gradual weight regain. People who maintain consistent meal patterns and avoid yo-yo dieting are more likely to sustain their weight loss over time. After the first month, maintaining momentum is key to weight loss maintenance. Some users opt for compounded Semaglutide with B12, which may enhance energy levels and metabolism for more consistent weight loss. The study used a mixed model for repeated measurements to analyze the data, but the statistical significance of the results was diminished after adjusting for body weight changes. 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. 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. Only 0.07 to 0.5 kg of the treatment difference between semaglutide and comparators was mediated by nausea or vomiting (indirect effects). Clinically relevant weight‐loss differences were observed across all BMI subgroups, with a trend towards higher absolute weight loss with higher baseline BMI. At the least, the new 7.2mg results point to scope for hiking the semaglutide dose in CagriSema to chase down that weight-loss target. Phase 3 results reported for CagriSema last month were a disappointment, however, with a 20.4% reduction in weight in the REDEFINE 1 study over 68 weeks that fell short of Novo Nordisk's hope of a 25% loss. It remains to be seen whether the data will help Novo Nordisk in its tussle for market share in the obesity market with Lilly, which reported head-to-head data in December showing that Zepbound was 47% more effective than the current dose of Wegovy. Written informed consent was obtained from all subjects before trial commencement. Semaglutide‐treated subjects followed a fixed‐dose escalation regimen to improve GI tolerability. Overall, 15.2% to 24.0% and 21.5% to 27.2% of subjects experienced nausea or vomiting with semaglutide 0.5 and 1.0 mg, respectively, versus 6.0% to 14.1% with comparators. Subjects were subdivided by baseline BMI and reporting (yes/no) of any nausea and/or vomiting. A new industry report uncovers the scope of a long-ignored problem in clinical trial operations. All trials were conducted in compliance with the International Conference on Harmonization Good Clinical Practice guidelines22 and the Declaration of Helsinki.23 The protocol was approved by local ethics committees and institutional review boards. The key inclusion/exclusion criteria were similar across the SUSTAIN 1 to 5 trials. The semaglutide 0.5 mg maintenance dose was reached after 4 weeks of semaglutide 0.25 mg once‐weekly, and the semaglutide 1.0 mg maintenance dose was reached after 4 weeks of semaglutide 0.25 mg once‐weekly, followed by 4 weeks of semaglutide 0.5 mg once‐weekly. We conducted a post hoc efficacy analysis by trial using all subjects in the global phase 3a SUSTAIN 1 to 5 randomized clinical trial programme. The data for SUSTAIN 7 were not available at the time of this analysis, and have therefore not been included.21 This results in gradual and sustainable weight loss when combined with a healthy, balanced diet and lifestyle changes. When used for weight loss, Semaglutide injections help people feel fuller for longer, leading to reduced calorie intake. However, side effects like nausea and digestive discomfort can also occur as your body adjusts. As more teenagers are living with obesity than ever before, researchers are searching for new treatments. Intriguingly, there was no difference in hypoglycemia between semaglutide and placebo. Placebo was the comparator in all studies, two of which included liraglutide (Rubino et al., 2022; O'Neil et al., 2018). Only one study included obese women with polycystic ovary syndrome (Jensterle et al., 2021). Subgroup and meta-regression analyses were elaborated to explore the heterogeneities in different baseline variables. Moreover, the sensitivity analysis was assessed to evaluate the stability and reliability of the results. Ultimately, in order to fully realize semaglutide’s potential to significantly address pediatric obesity, longer-term data and reductions in cost are needed. Clinical trial results and post-marketing reports can be used to guide clinicians when discussing potential risks, though data regarding associations between semaglutide and certain adverse effects, such as suicidal thoughts and behaviors, is particularly inconsistent. Given this data and the fact that obesity is a chronic disease, it is reasonable to surmise that youth may need lifelong therapy with semaglutide to prevent reoccurrence of obesity or weight regain. Adults treated with semaglutide 2.4 mg and lifestyle intervention regained two-thirds of their weight loss during the STEP-1 study after a year of semaglutide discontinuation (50). Although there is limited data, results from the STEP-Teens trial demonstrate rebound weight gain as early as seven weeks following discontinuation of semaglutide (13). We performed a retrospective review of the electronic medical records (EMRs) of patients in the Mayo Clinic Health System using semaglutide between January 1, 2021, and March 15, 2022. Multiple weight loss interventions have been developed during the past decades. Studies with longer periods of follow-up are needed to evaluate prolonged weight loss outcomes. By and large, our study was considered to be the latest and most comprehensive systematic review of randomized controlled trials, which fully examined the weight loss effects of different dosages of semaglutide compared with placebo in obese or overweight patients without diabetes. Clinical trials have demonstrated that semaglutide treatment can result in substantial reductions in body weight compared to placebo . It was repeatedly demonstrated throughout the PIONEER clinical trials (table 3) that the decrease in both HA1c and body weight was significantly greater with oral semaglutide when compared with a placebo.31–35 The superiority of oral semaglutide was also observed when compared with other oral antidiabetic medications, such as sitagliptin30 36 and empagliflozin.26 This superiority was also found in studies comparing oral semaglutide with other agents from the same drug class (dulaglutide37 and liraglutide33 34). However, when compared toaverage weight loss seen in major clinical trials of other FDA-approved medications,semaglutide 2.4 mg consistently showed greater weight loss and a greater proportionof patients achieving 5% body weight loss in STEP program trials.5,43 Additionally, semaglutide 2.4mg has fewer restrictions on its use than most other FDA-approved medications,excluding orlistat and liraglutide 3 mg. If patients do not tolerate the maintenance dose,the dose may be decreased to 1.7 mg for 4 weeks followed by escalation back tomaintenance dosing. Ifpatients do not tolerate a dose during escalation, clinicians should consider a4-week delay in dose escalation. Semaglutide for weight loss should be initiated at 0.25 mg once weekly and injectedsubcutaneously without regard to meals. Theelimination half-life of semaglutide is approximately 1 week; therefore, semaglutidewill be present for approximately 5-7 weeks after the last dose. GLP-1 is a target for weight management as it slows gastric emptying andpromotes satiety, which leads to a reduction in food intake. In fact, our results demonstrated the effectiveness and safety over 24 months of semaglutide treatment in T2DM obese subjects on loss of weight and HBA1C improvement.They usually look at your fasting blood sugar and/or HbA1c levels to understand how well the dose is working.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.The participants provided their written informed consent to participate in this study.Long-term weight loss effects of semaglutide in obesity without diabetes in the SELECT trial.It is worth noting that weight loss observed with semaglutide was mainly mediated by therapeutic effect, rather than the occurrence of those adverse events (Lingvay et al., 2020), indicating that semaglutide can be regarded as a weight management agent with generally acceptable safety. The effect of semaglutide (versus placebo) on mean percentage body weight loss as well as reduction in WC was found to be heterogeneous across several population subgroups.Rosenberg (2021) reports in his study on the effectiveness of once-weekly subcutaneous semaglutide administration combined with lifestyle interventions in achieving sustained, clinically relevant weight loss in obese or overweight adults.The Mayo Clinic institutional review board approved the study and waived the need for informed consent owing to its minimal-risk nature.The differences in subjects achieving ≥10% weight loss reached statistical significance in most BMI subgroups for semaglutide 1.0 mg, but less consistently for semaglutide 0.5 mg (Figure S1B, Supporting Information).In addition, this study could not assess the impact of maintenance semaglutide dose on patient response since the decision for the titration of semaglutide dose greater than 1 mg was influenced by the magnitude of three-month weight loss, introducing a selection bias.Trials evaluating the use of semaglutide at a dose of 1.0 mgwere excluded as this dose is not indicated for weight management purposes.Four studies (Wilding et al., 2021; Wadden et al., 2021; Rubino et al., 2022; O'Neil et al., 2018), including 3,612 individuals, noted a change in CRP, a marker of inflammation. Methods included a literature search of PubMed, MEDLINE, and Google Scholar, as well as identifying ongoing studies from clinicaltrials.gov. Results showed that semaglutide, whether injected or taken orally, led to a significant weight reduction. The study highlights the FDA approval of Wegovy for weight loss, emphasizing its effectiveness in reducing weight. 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. We treated diabetic patients with a personalized nutritional intervention, advice and information material for physical exercise according to the characteristics and possibilities of each patient. In the OS group at baseline mean HBA1C was 7.6 ± 1.6%. IS and OS therapy were well tolerated, and no patients in both groups experienced severe adverse events like nausea or vomiting. Weight loss of patients treated with Oral Semaglutide. The mW reduction was − 6.7 ± 5.3 kg (− 6.8 ± 5.8%); while the mBMI reduction was − 2.6 ± 2.1 kg/m2. Subsequently, eight studies involving 4,567 participants (Wilding et al., 2021; Wadden et al., 2021; Rubino et al., 2021; Rubino et al., 2022; O'Neil et al., 2018; Friedrichsen et al., 2021; Hjerpsted et al., 2018; Jensterle et al., 2021) were included in the meta-analysis. The remaining 28 studies were reviewed in full text, excluding trial registration records, duplicates of reporting, and non-English literature. A total of 474 studies were preliminarily retrieved from the databases, among which 55 were from ClinicalTrials. The primary outcome was a change in relative body weight from baseline to the longest follow-up. Semaglutide is contraindicated in patients with a personal or family history ofmedullary thyroid carcinoma (MTC), in patients with multiple endocrine neoplasiasyndrome type 2 (MEN 2) or in those with serious hypersensitivity reactions tosemaglutide or its excipients.13 Thyroid C-cell tumors were reported in rodent studies when treated withsemaglutide in a dose-dependent, duration-dependent manner. Five of these trials have been published.16-21 The results of STEP 5 werepresented at the 2021 Annual Meeting of the Obesity Society but have not beenpublished at the time of manuscript writing.20 Additionally, cardiovascular benefits of semaglutide 2.4 mg are beingevaluated in the SELECT trial, which is currently enrolling patients.22 Details of these trials are shown in Table 1. Future research should focus on addressing these gaps, particularly in exploring the long-term effects of semaglutide treatment and its integration with lifestyle modifications to optimize weight management outcomes. Meta-analyses evaluating the efficacy and safety between semaglutide and placebo in obese patients have been conducted previously. Liraglutide (Saxenda®, 3 mg), a glucagon-like peptide 1 receptor agonist (GLP-1RA) used for the treatment of type 2 diabetes, was approved by the FDA in 2014 for weight management in obese or overweight adults without diabetes (Pi-Sunyer et al., 2015; Scott 2015). In conclusion, the role of metformin in attenuation of weight regain after semaglutide discontinuation needs to be explored in randomized controlled studies in different insulin resistant populations. Five studies (Wilding et al., 2021; Wadden et al., 2021; Rubino et al., 2021; Rubino et al., 2022; O'Neil et al., 2018), including 4,424 individuals, displayed the proportion of participants who achieved weight loss of more than 5, 10, 15, and 20%. It was noted that WC reduction in semaglutide ranged from 6.11 to 14.88 cm, while the placebo ranged from 2.00 to 6.30 cm. Semaglutide, at any dose, displayed remarkably superiority to the placebo in losing weight. All eight studies were conducted on non-diabetic obese patients with an average baseline BMI of 33.8–40.1 kg/m2, and the individuals were all adults over 18 years of age (Wilding et al., 2021; Wadden et al., 2021; Rubino et al., 2021; Rubino et al., 2022; O'Neil et al., 2018; Friedrichsen et al., 2021; Hjerpsted et al., 2018; Jensterle et al., 2021). Literature searches were performed in PubMed, Cochrane Library, EMBASE, and ClinicalTrials.gov from their inception until 2 May 2022, using the search terms “obesity,” “semaglutide,” and “randomized controlled trial.” The retrieval was limited to English-language articles. It is known that throughout the world that approximately 40% of adults are overweight and more than 15% of subjects are living with obesity.Indeed, in our first on-treatment analysis at week 208, weight loss was greater (−11.7% for semaglutide) compared with the in-trial analysis (−10.2% for semaglutide).The systematic review will focus on studies involving adults aged 18 years and older to ensure the findings apply to the adult population.In vitro studies have shown a low potential for semaglutide to affect CYP enzymes orinhibit drug transporters.In addition, a new generation of studies should recognize distinct obesity phenotypes and evaluate the use of semaglutide for weight management in patient subgroups with different main comorbidities with primary end points other than weight, for example, the progression of liver steatohepatitis or the regression of liver fibrosis .Semaglutide was generally well tolerated by the teenagers with obesity in this study, and serious medication side effects did not happen very often.How long you take a weight-loss drug depends on whether your body is responding to it.Has received speaking or consultancy fees from AstraZeneca, Lilly, Merck, Novo Nordisk and Sanofi; research funding for clinical trials (all paid to the institution) from AstraZeneca, Boehringer Ingelheim, Lilly, Mannkind Corporation, Medtronics, Mylan Pharmaceuticals, Novo Nordisk and Sanofi; and travel funding from AstraZeneca, Lilly, Novo Nordisk and Sanofi. In order to facilitate clinical application, semaglutide should be investigated as a conventional weight-lowering drug for normal obese patients without diabetes, and the weight loss effect should be evaluated by different doses; furthermore, the potentially beneficial effects could be sought. Compared with placebo, semaglutide administered subcutaneously reduced body weight by 10.09% (10.54 kg), BMI by 3.71 kg/m2, and WC by 8.28 cm, achieved more than 5, 10, 15, and 20% weight loss with a higher proportion of participants, and exhibited certainly positive effects on blood pressure, CRP, and lipid profiles. Subgroup analyses of RBW and ABW changes between semaglutide and placebo based on specific doses were carried out, as shown in Supplementary Tables S4, S5, indicating that the higher the dose, the better the body weight reduction effect. Overall, during semaglutide treatment phase, from timepoint 1 to timepoint 2, women lost a significant amount of body weight. We aimed to explore changes in body weight, cardiometabolic and endocrine parameters in obese women with PCOS who continued metformin treatment 2 years after semaglutide cessation. To date, the amount of weight regain after semaglutide withdrawal in patients with obesity continuing metformin treatment, including obese women with PCOS, has not yet been evaluated. STEP 4 directly compared the effect of semaglutide continuation versus semaglutide discontinuation on body weight (9). Weight loss not explained by nausea or vomiting was a consequence of a direct effect of semaglutide. This is also in line with studies of other GLP‐1RAs, in which the most commonly reported AEs were typically GI in nature and included nausea, vomiting and diarrhea.11, 12 In the case of exenatide ER, it may be related to its exendin‐4‐derived structure, which has a much lower amino acid sequence homology to native human GLP‐1 than semaglutide. Therefore, semaglutide has become the first AOM that results in a greater than 10% average weight loss over that attributable to lifestyle interventions , generating widespread public interest and leading to global supply shortages. In 2021, semaglutide was approved by both the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for chronic weight management in patients with either a BMI greater than 30 kg/m2 or a BMI greater than 27 kg/m2 and at least one weight-related condition. This is a retrospective chart review of 40 overweight or obese individuals with a median age of 47 years, weight of 111.7 kg, and body mass index (BMI) of 39.7 kg/m2 who were prescribed semaglutide for weight management. Has received consultancy fees (all paid into University funds) from GW Pharma, Janssen, Lilly, Merck, Novo Nordisk, Orexigen and Takeda; research grants for clinical trials from Janssen, Novo Nordisk, Sanofi and Takeda; and travel grants for conference attendance from Janssen and Novo Nordisk. Has received speaking or consultancy fees from AstraZeneca, Lilly, Merck, Novo Nordisk and Sanofi; research funding for clinical trials (all paid to the institution) from AstraZeneca, Boehringer Ingelheim, Lilly, Mannkind Corporation, Medtronics, Mylan Pharmaceuticals, Novo Nordisk and Sanofi; and travel funding from AstraZeneca, Lilly, Novo Nordisk and Sanofi. In SUSTAIN 3, the difference compared with exenatide ER was present across all BMI groups. Weight loss was generally more pronounced in subjects who experienced nausea or vomiting compared with those who did not experience such events. Overall, nausea and vomiting events were mostly transient, with a median duration of between 1 and 8 days with the semaglutide 0.5 and 1.0 mg and comparator groups. These results were broadly similar to the overall population and to those with a baseline BMI 2, with the exception of SUSTAIN 3 (10% threshold) and SUSTAIN 5 (5% and 10% thresholds), in which proportionately fewer subjects achieved these targets than in those with low baseline BMI (Figure S1, Supporting Information). If it’s close to the time for your next scheduled dose, just skip the missed dose. If you miss a dose, take it as soon as you remember. It's crucial to assess potential drug interactions and ensure treatment is tailored to your individual needs. Addressing obesity is crucial because it significantly impacts both physical health and quality of life. Therefore, of the overall greater weight loss observed with semaglutide versus comparators (2.3 to 6.3 kg), most of this reduction (2.2 to 5.9 kg) was not explained by nausea or vomiting (direct effects) (Figure 2). There were, however, no overall BMI‐dependent effects on relative weight loss across the trials. Among heavier subjects (baseline BMI ≥35 kg/m2), the proportions achieving ≥5% weight loss were 30% to 49% and 47% to 68% of those receiving semaglutide 0.5 and 1.0 mg, respectively, versus 6% to 27% receiving comparator treatments. It remains unclear to what extent weight loss, the improvement of metabolic risk factors, and possible pleiotropic anti-atheroslcerotic effects contribute to the semaglutide-related reduction of cardiovascular risk . A semaglutide dose of 1 mg, lower than the approved maintenance dose of 2.4 mg per week, was prescribed in the long term for more than half the individuals in this study, leading to a median six-month weight loss of 13.6%. These weight loss outcomes are comparable with a three-month percentage weight loss of 6%-6.5% and six-month of 10.6%-12% reported in STEP 1 and STEP 4 trials 7,8, suggesting that semaglutide achieves a similar effect in routine clinical practice with that observed in RCTs. This study reported semaglutide-related percentage weight loss of 6.6% (7.4 kg) and 13.3% (14.9 kg) in three and six months, in line with the mean 6.3% and 11.8% in three and six months, respectively, observed in a similar real-world cohort study in the United States . With respect to the impact of semaglutide on glycemic control, three-month semaglutide treatment resulted in the median reduction of fasting glucose by 6 mg/dL from a baseline value of 99 mg/dL, while four out of 11 participants (36.3%) with HbA1c in the range of prediabetes at the baseline reverted to normal HbA1c levels. Despite its robust design, the study notes an inflexible run-in period and no assessment of adherence to lifestyle interventions, which could impact the interpretation of weight maintenance results.A chi-squared test was employed to assess the gender distribution of non-responders to semaglutide who were defined as individuals who achieved neither a three-month weight loss of 3% nor a six-month weight loss of 5%.Intervention with the latest AOMs even results in 20% weight loss and is already approaching the effectiveness of bariatric surgery.Change from baseline in body weight was assessed within each trial and subgroup.Remediating the adverse health effects of excess abnormal body fat through weight loss is a priority in addressing the global chronic disease burden.Every breakthrough in medicine, every new treatment that changes lives, starts with research.The accuracy of parameters used to discriminate between basal and post-treatment values were evaluated using ROC curve analyses.This could mean starting with a lower dose, taking more time to increase the dose, or using a lower maintenance dose.Gall bladder-related issues, including cholelithiasis, ranged between 0.2% and 4.9%, and cardiovascular issues, including tachycardia and arrhythmias, ranged between 1.5% and 9.8% in STEP trials 1–4. 46 patients in the OS group had a mW and mBMI reduction of - 6.7 ± 5.3 kg and - 2.6 ± 2.1 kg/m2. Patients achieved a TBWL of 13.4 (8.0)% at 12 months (p p Semaglutide demonstrated notable improvement in obesity, metabolic, and cardiovascular disease risk outcomes in a clinical setting. We included 304 patients (73% female, 93% White, mean age 48.8 12.4 years, BMI 40.9 9.6 kg/m2) in the analysis. We excluded patients with bariatric surgeries, taking other anti-obesity medications, and with active malignancy or pregnancy. Safety profile - the safety profile of semaglutide was generally favorable, with most adverse events being mild to moderate in severity. Studies focusing on populations with diabetes or other specific conditions (e.g., cardiovascular disease). A comprehensive search will be conducted in electronic databases (e.g., PubMed, Embase, Cochrane Library) for relevant RCTs published up to the present date. Zhang found that a weekly dosage of 2.0 mg or higher was most effective, particularly in those with severe obesity . 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. Despite its robust design, the study notes an inflexible run-in period and no assessment of adherence to lifestyle interventions, which could impact the interpretation of weight maintenance results. In a clinical review by Fornes et al., the efficacy and safety of once-weekly semaglutide 2.4 mg for weight management are examined. The study underlines the practical implications of Wegovy’s approval, making it a viable option for weight management. 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. 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. 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. At the baseline, all individuals underwent screening for prediabetes and diabetes, with the diagnosis of DM being an exclusion criterion. Individuals were started on semaglutide in the time period between November 2021 and November 2022, with no more patients initiated on semaglutide afterward due to its supply shortages. This is a retrospective review of the medical records of all individuals treated with semaglutide for weight management in an endocrine clinic in Athens, Greece. Weight changes ranged between 3.6% and −14.3% at 3 months and between −0.6% and −29.1% at 6 months. Mean values of fasting glucose, hemoglobin A1c, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides at baseline are presented in Table 1. For secondary end points, categorical data were analyzed using the Fisher exact test, and the 2-sample independent t test was used for continuous data. During data abstraction, we confirmed the medication start date from physicians’ EMR notes or physician-patient communications because there might be a delay between the day of prescription and the start of medication (eg, insurance approval delay and drug availability). These findings have led to the approval of semaglutide 2.4 mg (marketed as Wegovy) by regulatory agencies, including the FDA, for chronic weight management in adults with overweight or obesity. The clinical trials typically involved participants taking semaglutide for 68 weeks or more. Once-weekly semaglutide aids weight loss by targeting hunger signals and blood sugar regulation. Semaglutide is an FDA-approved medication originally developed to treat type 2 diabetes but has gained widespread popularity for its weight loss benefits. Semaglutide was generally well tolerated by the teenagers with obesity in this study, and serious medication side effects did not happen very often. For adults with T2D, semaglutide subcutaneous at doses of 2.4 mg or 1.0 mg decreased mean hemoglobin A1c by 1.6% and 1.5%, respectively, versus a reduction of 0.4% among participants assigned placebo (16). Additionally, 53% of those treated with semaglutide experienced a ≥15% reduction in BMI compared to 5% in the placebo group. A greater proportion of participants treated with semaglutide (73%) experienced a reduction in BMI of ≥5% compared to 18% of the placebo group. In 2022, subcutaneous semaglutide, up to a dose of 2.4 mg once weekly, was FDA-approved as an adjunctive agent to lifestyle modifications for chronic weight management in pediatric patients 12 years or older with a BMI ≥ 95th percentile for age and sex. The purpose of this review is to describe the existing limited data related to the use of semaglutide in adolescents with obesity, supplementing with findings from adult studies of semaglutide use. Second, previous studies based on semaglutide in obese patients with or without diabetes had been published, potentially affecting the innovation of our research; thus, some other aspects were discussed, such as the narrowing of patients, the specific dose of semaglutide, and the potentially beneficial effects on cardiovascular disease. First, because of the relatively limited number of studies about semaglutide treating obesity without diabetes, one of our studies was divided into seven separate trials for analyses, which might affect the homogeneity and publication bias. First, the latest and most comprehensive systematic review examining the weight loss effects of semaglutide was totally conducted in obese or overweight patients without diabetes, which is expected to provide favorable strategies for normal obese patients as a conventional weight-lowering drug. The previous studies were almost referred to patients with or without diabetes and the comparison between 2.4 mg-dosed semaglutide and placebo.