After 6 and 12 months mean changes in HbA1c (Figure 1), FBG and body weight were statistically significant and clinically relevant. This was a multicenter, observational, retrospective study, aiming to investigate the use and the impact of OW semaglutide after 6 and 12 months of treatment. As known, real-world studies allow to assess whether the results of experimental studies can be reproduced in broader samples of patients managed under routine clinical practice (24). Although the studies in the current evidence networks were sufficiently homogeneous to perform NMAs, some variability was observed between the trials in terms of study designs and patient populations. The current SLR and meta-analysis was performed to identify and compare RCT evidence for weekly semaglutide 2.4 mg with that of relevant pharmacological comparators for weight management in overweight or obesity. When considered against active comparators, semaglutide also increased the likelihood of participants losing ≥5% fasting body weight, with ORs ranging from 1.29 (95% CI 0.70, 2.13 T2DM) to 2.17 (95% CI 1.44, 3.27 NGT) with liraglutide 3.0 mg and from 6.09 (95% CI 2.86, 11.95 total population) to 7.75 (95% CI 5.29, 11.37 non-T2DM) with orlistat 120 mg three times daily (TID). All trials were blinded except one that was not blinded and the authors acknowledged that this prevented them from determining the independent effect of orlistat.40 In a second study, the extent of blinding was unclear but the potential impact on results was not discussed.41 All studies used an intention-to-treat (ITT) analysis except for two in which this was unclear42,43 and two that did not use an ITT analysis. To account for the potential impact of IBT on the outcomes of the NMA, these five trials were excluded from the networks (although it is noted that participants in the remaining studies in the network may also have received dietary and exercise advice). Aim to lose 1 to 2 pounds (0.5 to 1 kilogram) a week over the long term. What will give you the burning desire to stick to your weight-loss plan? No one else can make you lose weight. Here are six tips to help you start your weight-loss journey. Veterans with medications, procedures, or conditions that couldsignificantly affect weight were excluded. Novo Nordisk was granted a label expansion soon afterward for dose of 2.0 mg for persons with T2D whose hyperglycemia remained uncontrolled by other agents.5 These latest findings add to the growing evidence on the effect of semaglutide addressing cardiovascular disease.”2 “For people with obesity and existing cardiovascular disease, preventing another heart attack or stroke is vitally important,” Jason Brett, MD, principal medical head at Novo Nordisk Inc, said in the statement. The studies were conducted in accordance with the local legislation and institutional requirements. Semaglutide has demonstrated the largest weight loss of any obesity medication to date with reductions of approximately 15% of initial weight at 68 weeks, accompanied by improvements in cardiovascular risks factors and physical functioning.I use it simply as a benchmark and quantify the weight change within each individual in the study group.Claims data are subject to miscoding or misclassification of diagnosis codes.Emerging algorithms based on the pathophysiology of obesity should provide the most effective sequencing of AOM and emphasize the importance of a dynamic interplay of different modalities combined with lifelong lifestyle intervention.Some side effects, such as appetite changes, can actually be signs that the medication is working as intended, helping to reduce calorie intake and support weight loss.The medication may still be working behind the scenes, and the benefits often become more noticeable with time and as the dose increases.In November 2021, the EMA extended the dose of once-weekly subcutaneous semaglutide up to 2 mg for the treatment of T2D.46 Of note, an oral tablet form of semaglutide (Rybelsus® Novo Nordisk A/S, Bagsværd, Denmark 3, 7 and 14 mg) had previously been approved in the USA in September 2019 and in Europe in January 2020 for the treatment of T2D.48,49 Due to the need for these approvals to be achieved, this drug has only recently become available on the market.The data for SUSTAIN 7 were not available at the time of this analysis, and have therefore not been included.21 A plateau happens when your body adjusts to changes from medication, diet, or exercise, causing your progress to slow or stop. This can be frustrating, especially if you’ve been following your treatment plan closely. This is especially important if you experience severe side effects, new or worsening symptoms, or signs of dehydration. For Rybelsus (the oral form), taking it incorrectly (e.g., not on an empty stomach) can affect absorption. Skipping doses or not following the prescribed instructions can lead to slower results. Wegovy (semaglutide) is not only superior at reducing body weight compared with other antidiabetic drugs, but it is also cardioprotective. A higher incidence of retinopathy complications, including vitreous hemorrhage and blindness, was reported in patients treated with semaglutide compared with placebo.16 This was considered to be related to the rapidity and magnitude of glycemic improvement rather than a direct side effect of semaglutide. 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 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. The estimated treatment difference was from baseline to Week 30 for SUSTAIN 5 and from baseline to Week 40 for SUSTAIN FORTE.Three months following semaglutide initiation, the administered dose was 1 mg for all participants.The most reliable information comes from large clinical trials.RLB contributed to the conduct of the trial, data collection, analysis and interpretation and manuscript development.This real-world study showed an early improvement in glycemic markers, confirming the glucose-lowering effect reported in STEP studies 7-9.I didn’t think about weight that much.Patients will benefit from potential weight loss, improved metabolic health, and enhanced overall well-being through structured medical supervision and nutritional support.Even in clinical trials, semaglutide was found to be effective in weight loss when combined with lifestyle changes.Previous studies in the STEP trial program have been limited to treatment durations of up to 68 weeks6–8.Due to its substantial and durable weight loss effect, semaglutide may herald a new era in the management of obesity, using percentage weight loss as a biomarker and applying a treat-to-target approach, in line with other chronic diseases, to prevent and treat weight-related complications . Key points regarding baseline characteristics and study outcomes for the major cardiovascular outcome trials in human GLP-1RA are summarized in Table 1. The ELIXA trial was designed to assess the cardiovascular safety of lixisenatide in high-risk T2D patients who had suffered acute coronary syndrome in the past 180 days.25 This multicenter RCT recruited 6068 individuals and over a follow-up of 25 months, showed non-inferiority of lixisenatide compared with placebo in relation to the composite primary endpoint of death from cardiovascular causes, nonfatal MI, nonfatal stroke, and hospitalization for unstable angina HR 1.02 (0.89 to 1.17). The LEADER trial randomized high-risk individuals with T2D to liraglutide or placebo5 and enrolled 9340 patients. 4. Weight loss by GI AEs—post hoc analysis The average placebo-subtracted weight loss for semaglutide was 12.7 kg.21 Semaglutide has generated much scientific, clinical, and public excitement and interest given these large weight losses. At the longest follow-up, 33.4% of participants randomized to semaglutide achieved ≥20% weight loss compared with 2.2% with placebo (RR 15.08, 95% CI 9.31 to 24.43). However, its effects on sustained weight loss in patients without diabetes remains unclear. These cardiovascular benefits make SEMAGLUTIDE a valuable tool for long-term health management, particularly for patients prone to heart disease or stroke. SEMAGLUTIDE addresses multiple cardiovascular risk factors, making it an essential medication for high-risk patients. Cardiovascular health is a top concern for individuals with T2D or obesity. Semaglutide’s dual action, stimulating insulin and suppressing glucagon, helps patients achieve better glycemic control while improving overall metabolic health. The measurable concentrations of oral semaglutide of those in the fasted state compared to those in the fed state indicate that the absorption of oral semaglutide is hindered by the presence of food in the stomach and to improve its absorption and overall exposure, oral semaglutide should be taken in the fasted state . Plasma concentrations of oral semaglutide indicated that its absorption occurred early on, and once in the systemic circulation, it had a slow elimination rate. There are a few good reviews on oral semaglutide including Bucheit et al. and Anderson et al. and this review hopes to add to the gaining literature and, more specifically, the safety and efficacy 20, 21. Administration of Semaglutide Oral Tablets Also, Dr Greenway served on the Novo Nordisk advisory board for the development of liraglutide that is now approved and was a comparator drug in the trial described in the present article. Starting so high in weight and losing as much as I have means I have excessive loose skin. What matters is that you took that step to be better! Your journey can look different from mine, and your side effects can be more or less intense than what I experienced. You’re not taking the easy way out, you’re using a tool to help you better learn how to manage your weight. In a separate analysis, subjects in the SUSTAIN 1 to 5 trials were subdivided according to whether or not they had spontaneously reported any nausea and/or vomiting GI AEs. Subjects in the SUSTAIN 1 to 5 trials were subdivided by baseline BMI (2), from a baseline BMI range of 16.35 to 72.84 kg/m2. Analyses were based on data from subjects while they were on treatment without using rescue medication. Other secondary endpoints presented in these analyses were the proportions of subjects achieving ≥5% or ≥10% weight loss, and safety parameters including AEs.15, 16, 17, 18, 19 In the pre‐planned analyses, the key endpoints were similar across all of the SUSTAIN 1 to 5 trials. This article will provide a clear, detailed explanation of how fast semaglutide works. Understanding how quickly semaglutide starts working is important for people who take it. Because of its effectiveness, many people want to know how fast it works—whether for lowering blood sugar, reducing weight, or both. It belongs to a class of drugs called GLP-1 receptor agonists, which work by mimicking a hormone in the body that helps control blood sugar and appetite. An additional study compared weight loss outcomes for semaglutide and tirzepatide but used data specifically for these medications labeled for T2DM and thus included a large (52%) proportion of patients with T2DM. In this real-world setting, patients who were treated with semaglutide 2.4 mg and tirzepatide had a mean weight loss of − 14.1% and − 16.5% at 1 year, respectively, which represents a clinically meaningful weight loss with both therapies when used in patients with overweight or obesity and without T2DM . This study demonstrated the real-world effectiveness of semaglutide 2.4 mg and tirzepatide treatment in patients with overweight or obesity and without T2DM over a 1-year follow-up period. After 1 year of treatment, patients who received semaglutide 2.4 mg or tirzepatide achieved clinically meaningful weight loss This retrospective study examined real-world weight loss outcomes over 1 year of follow-up in patients with overweight or obesity and without T2DM who were treated with semaglutide 2.4 mg or tirzepatide Mean observed change in body weight over time during the in-trial period is shown as percentage change in Fig.There is also high recidivism and minimal success for commercial and community-based weight loss programs 23,41.The most recent (July 2021) Italian guidelines for the management and treatment of T2D recommend metformin, sodium-glucose co-transporter-2 inhibitors (SLGT-2is) or glucagon-like peptide-1 receptor agonists (GLP-1RAs) as first-line treatment options in patients with T2D and previous CV events (without heart failure) (12, 13).The study, published in the Annals of Internal Medicine, found that semaglutide significantly increased weight loss but also caused gastrointestinal disorders in participants.While semaglutide is a powerful weight loss tool, it’s important to set realistic goals for your weight loss journey.All the participants were advised to follow the standard lifestyle modifications similar to STEP 5 trial.For the purposes of this study, “unintended weight loss”refers to a therapy’s unexpected, additional effect on weight reduction. A total of 1853 patients (54.7%) were female and 1536 (45.3%) were male, and 2785 (82.2%) had T2D as a treatment indication. To assess the robustness of the identified association between medication and 10% or greater weight loss at 1 year, we conducted sensitivity analysis. Sociodemographic variables, including patients’ age, sex, race and ethnicity, primary payer type, and Area Deprivation Index (ADI) based on census block group neighborhood-level data24 were recorded from the primary care visit closest to the index date. Given the nature of observational studies, data could have been confounded, since patients with diabetes whom have an indication for GLP-1RA therapy often have concomitant risk factors for pancreatitis (notably obesity, longer diabetes duration and co-medication). In a mediation analysis of the SUSTAIN 1 to 5 trials, a small component (0.07 to 0.5 kg) of the total treatment difference in weight loss was explained by nausea or vomiting (52). Generally, the GI complaints with semaglutide occur in the first 8–12 weeks of treatment during dose escalation in contrast to for example liraglutide, where they occur within 2 weeks (17, 32), and wane over time (Figure 2). As a clear example in the abovementioned phase 2 study (38), 77% of patients experienced GI adverse effects when a fast 2-week dose escalation was used to reach 40 mg compared with 54% in the slower 8-week dose-escalation group. When compared with placebo, subcutaneous semaglutide for 30 weeks induced nausea in 11.4 to 20% of the semaglutide-treated patients (placebo 3.3–8%), vomiting in 4 to 11.5% (placebo 2–3%) and diarrhea in 4.5 to 11.3% (placebo 1.5–6%) (10, 27, 31). Our findings provide timely data on longer-term weight outcomes in patients receiving treatment with injectable semaglutide or liraglutide for obesity or T2D and identify key characteristics that could inform the probability of achieving sustained weight loss of a magnitude large enough to provide clinically significant health benefits.20,21 The primary outcome measures in this study were (1) percentage of weight change at 1 year following initiation of injectable semaglutide or liraglutide treatment and (2) categorical weight loss of 10% or greater at 1 year, given that sustained weight loss of 10% or more in patients with obesity has a major beneficial impact on obesity-related comorbidities.20,21 Baseline BMI was calculated using the weight data captured on the index date or, if not available, within 6 months before the index date. In this cohort study of 3389 patients with obesity, the mean percentage of body weight change from baseline to 1 year was −5.1% for semaglutide vs −2.2% for liraglutide treatment; −3.2% for type 2 diabetes vs −5.9% for obesity indications; and −5.5% for patients with persistent medication coverage vs −2.8% with 90 to 275 coverage days and −1.8% with fewer than 90 coverage days. Ji et al. (2021) revealed that semaglutide was related to a significant 26% reduction in the risk of major adverse cardiovascular events compared with placebo, with a 39% reduction in stroke. GLP-1RA has been reported to reduce body weight through a variety of pathways, including inhibiting gastrointestinal peristalsis and gastric secretion, prolonging gastric emptying, lessening energy intake, as well as generating satiety and suppressing appetite via the central nervous system, especially the hypothalamus (Zander et al., 2002; Drucker 2018). Sensitivity analyses of two main outcomes, namely, RBW change and the proportion achieving 5% weight loss, were carried out through Stata 14, as shown in Supplementary Figures S2, S23. The reason for statistical heterogeneity might be inconsistent dose and duration of administration between studies. Seven studies (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; Jensterle et al., 2021), including 4,537 individuals, reported the proportion of participants with nausea and diarrhea. 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 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. Data for the placebo groups are presented in eTable 5 in Supplement 3. The primary end point result could not be reversed in the tipping point analysis because of the small amount of missing data. Weight loss with semaglutide was significantly greater vs with liraglutide (difference, –9.4 percentage points 95% CI, –12.0 to –6.8; P Table 2). The presence of prediabetes was determined by investigators on the basis of available information (eg, medical records, concomitant medication, and blood glucose variables) and in accordance with American Diabetes Association criteria.18 The main primary endpoints were percentage change in body weight and the proportion of participants with ≥5% weight loss from baseline (i.e. at randomization; week 20 in STEP 4) to week 68, without weight regain. The programme compared 2.4 mg semaglutide with placebo, as an adjunct to lifestyle interventions (500 kcal/day deficit relative to the estimated total energy expenditure, plus 150 minutes/week of physical activity) (except for STEP 3; see below), in people with obesity or overweight (and T2D in STEP 2). In November 2021, the EMA extended the dose of once-weekly subcutaneous semaglutide up to 2 mg for the treatment of T2D.46 Of note, an oral tablet form of semaglutide (Rybelsus® Novo Nordisk A/S, Bagsværd, Denmark 3, 7 and 14 mg) had previously been approved in the USA in September 2019 and in Europe in January 2020 for the treatment of T2D.48,49 Due to the need for these approvals to be achieved, this drug has only recently become available on the market. Initially developed as treatment for type 2 diabetes and marketed as Ozempic, it won F.D.A. approval for chronic weight management in 2021. This ultimate guide covers how long to take semaglutide, what your weight loss journey will look like, and how to maintain your results long term. Semaglutide has arrived as a truly revolutionary drug for the treatment of obesity and severe weight problems. A weight regain of 11.6% in the semaglutide group and 1.9% in the placebo. Peer review Get expert advice from our team of registered dietitians to make losing weight feel easier while on medication. We hope that our 6+ years of working with the NHS and building a track record of effective weight-loss results will give you peace of mind to give us a try. Second Nature has worked with the NHS for over 6 years providing weight-loss programmes across the UK. Moreover, 5 patients (2.9%) had to stop semaglutide because of the intolerability of the adverse effects, while 15 (8.6%) had to either reduce the dose or remain on the same dose to avoid exacerbation of the adverse effects. In our study, 77 patients (44.0%) received the highest current doses of subcutaneous semaglutide (1.7 and 2.4 mg), while 98 (56.0%) received lower doses (0.25, 0.5, and 1 mg). We performed a post hoc analysis of patients with or without type 2 diabetes and of patients receiving different doses of semaglutide. Secondary end points were the proportion of patients achieving weight loss of 5% or more, 10% or more, 15% or more, and 20% or more after 3 and 6 months and the percentage of weight loss for patients with or without type 2 diabetes after 3 and 6 months. As mentioned, the starting dose of 0.25mg is intentionally low. If you have type 2 diabetes, you might see somewhat different results. Because you're starting at this low dose, your first-month results will typically be more modest than what will happen in later months. Research shows that people taking semaglutide naturally reduce their daily calorie intake by about 24% compared to those not taking the medication. Wegovy has a higher maximum dose of 2.4mg (versus 2mg for Ozempic). The primary end point was the percentage weight loss at three and six months after semaglutide initiation. All individuals received counselling sessions about nutrition and regular exercise at the time of semaglutide initiation and every 12 weeks thereafter by an endocrinologist, following the principles of motivational interviewing. Thereafter, according to the standard titration regimen , the dose was increased after four weeks to 0.5 mg and after eight weeks to 1 mg. Semaglutide use required patient self-funding and was commenced at a dose of 0.25 mg once weekly for the first four weeks. 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 this case, the target weight is essential, as I recommend that patients stay on the medication until they reach the target. However, obese and non-obese patients may have weight goals that are beyond that. Without such support, compounded semaglutide may be a good alternative and adjunct to achieving calorie restriction and weight reduction. The calorie restriction compliance was aided by intensive, weekly behavioral therapy and food and calorie calculation support. People can lose on average anywhere from five to 20 percent of their weight on these drugs in one year, depending on their starting point, research has found. XW and WX helped to extract the data, analyze the data, and review the manuscript. XG and XH performed the literature search, extracted the data, analyzed the data, and wrote the manuscript. Semaglutide works by mimicking the action of this hormone, helping to improve blood sugar control and support weight loss. Semaglutide is a medication used to help people manage type 2 diabetes and lose weight. This information is important for people considering semaglutide as a treatment option and for those already using it who want to know what to expect. The medication comes in different forms—Ozempic and Wegovy are injections taken once a week, while Rybelsus is a daily oral tablet. For blood sugar control, improvements may begin within the first week, but it often takes a few months for full effects. J.P.F. contributed to acquisition, analysis or interpretation of data; critical revision of the manuscript for important intellectual content; and supervision. L.N.C. contributed to analysis and interpretation of data; critical revision of manuscript for important intellectual content; and statistical analysis. Contributed to concept and design; acquisition, analysis or interpretation of data; drafting of the manuscript; and critical revision of the manuscript for important intellectual content. However, the use of pharmacologic therapy has been limited by moderate efficacy, significant side effects, and poor affordability.Work up to at least 30 minutes of aerobic exercise most days of the week.Based on the example of statins over the last 30 years, and with the proviso that the evidence regarding the benefits of semaglutide continues to accumulate in the years to come, one may hope that this agent will be used and reimbursed in both primary and secondary prevention and intervention.Improvements were observed in some cardiovascular risk factors from baseline to week 120 (Figures 2 and S3 and Table 2), including for LDL cholesterol and CRP in both semaglutide and placebo arms and for HDL cholesterol, VLDL cholesterol and triglycerides in the semaglutide arm.We used 12 randomized clinical trials (RCTs) in our study and assessed the risk of bias using the Cochrane Risk of Bias tool (Figure 3).It aids calorie restriction at significantly lower doses. Overall, oral semaglutide 7 mg and 14 mg proved to be superior to sitagliptin for a reductions in HbA1c and BW in this study . Gastrointestinal AEs were also the primary cause of premature trial product discontinuation with 5.6%, 5.8%, and 11.6% of subjects receiving oral semaglutide 3 mg, 7 mg, and 14 mg, respectively, compared with 5.2% receiving sitagliptin therapy. Additionally, oral semaglutide showed greater mean changes from baseline in BW at week 26 compared with sitagliptin (Table 1). Second Nature’s medication programme Weight loss effects may begin within the first few weeks, but more noticeable changes often occur after 8-12 weeks of consistent use. Semaglutide can start to affect blood sugar levels within the first week of treatment, but significant results typically take a few weeks to become noticeable. Speaking of side effects, it’s worth mentioning that some people experience symptoms like nausea, vomiting, or diarrhea, especially when first starting semaglutide or increasing the dose. Real-world data show weekly semaglutide effective for weight loss at 3, 6 months In terms of race and ethnicity, 689 patients (20.3%) were Black, 237 (7.0%) were Hispanic, 2320 (68.5%) were White, and 116 (3.4%) were of other race or ethnicity. For these, we excluded the patients who switched between the medications of interest from the multivariable logistic regression model. Pearson χ2 test, 2-sample t test, and Wilcoxon rank sum test were used for comparisons of baseline variables.26 The mean percentage weight change at 1 year was compared using a 2-sample t test or analysis of variance.26 The number of reported serious side effects was higher with liraglutide (11%) compared to semaglutide (7.9%) or placebo (7.1%). From baseline to week 68, greater reductions in abdominal visceral fat area were observed in the semaglutide 2.4 mg (−40%) and 1.7 mg (−22.2%) groups than the placebo group (−6.9%). The number of reported serious side effects was unexpectedly lower in the semaglutide arm contrasted with the placebo arm (7.9% vs. 11.8%). In contrast with the switched placebo arm, the most commonly documented side effects in ≥5% of the continued semaglutide arm included diarrhoea (14.4% vs. 7.1%), nausea (14.0% vs. 4.9%), constipation (11.6% vs. 6.3%), nasopharyngitis (10.8% vs. 14.6%), and vomiting (10.3% vs. 3.0%). The number of serious side effects was higher in the continued semaglutide arm contrasted with the switched placebo arm (7.7% vs. 5.6%). Similarly, someone with more weight to lose may not notice changes as quickly as someone with less to lose, even though both are making progress. Factors like age, genetics, and hormone levels can affect how fast semaglutide works. This slow increase means that it may take time to reach the dose that’s most effective for you. Some people may notice changes quickly, while others may take longer to see improvements in their blood sugar levels or weight. However, the way semaglutide works can be different for everyone. Patients are advised to consult their HCP about treatment-related questions. Get patients started at Wegovy.com 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. The trial product estimand addressed the average treatment effect in all randomly assigned participants, assuming that the drug or placebo was taken as intended (participants on treatment). Participants discontinuing treatment prematurely remained in the trial and were encouraged to attend scheduled visits, particularly those at weeks 104 and 111. Semaglutide was initiated at 0.25 mg per week for the first 4 weeks via a pre-filled pen injector, escalating in a fixed-dose regimen every 4 weeks to reach the maintenance dose of 2.4 mg by week 16 (lower maintenance doses were permitted if participants were unable to tolerate 2.4 mg) (Extended Data Fig. 1). In addition, semaglutide treatment reduced C-reactive protein levels, a marker of systemic inflammation that is known to be elevated in patients with obesity25,26. ObesityWeek Subjects had a mean age of 55 years, an HbA1c between 7.0 and 9.5%, and received the maximally tolerated dose of metformin with or without a sodium-glucose cotransporter-2 inhibitor (Table 4). AUC24,Day10 area under the plasma concentration–time curve from time zero to 24 h after the tenth dose, Cmax,Day10 maximum plasma concentration 0–24 h after the tenth dose, ESRD end-stage renal disease, h hour, t1/2 terminal half-life, tmax,Day10 time to reach Cmax,Day10 Overall, no systematic differences in the proportion of subjects reporting AEs were observed between treatment groups . Its effectiveness has been proven in many clinical trials, and it is now widely used under different brand names like Ozempic, Wegovy, and Rybelsus. Some side effects, such as appetite changes, can actually be signs that the medication is working as intended, helping to reduce calorie intake and support weight loss. Most side effects, like nausea, diarrhea, and loss of appetite, tend to appear early in treatment, especially when starting the medication or increasing the dose. They occur because your body adapts to changes in metabolism, weight, and medication effects over time. It’s important to understand that semaglutide works gradually, especially since it’s often started at a low dose and slowly increased to minimize side effects. Early treatment can prevent these problems. Many of these symptoms, especially fatigue and weight gain, are common and do not necessarily mean you have a thyroid problem. Myxedema coma requires immediate medical treatment. Rarely, severe untreated hypothyroidism may lead to myxedema coma, an extreme form of hypothyroidism in which the body’s functions slow to a life-threatening point. Many women taking thyroid hormone medicine need a higher dose during pregnancy, so contact your doctor right away if you find out you’re pregnant. Strengths of this study include its large and diverse sample (including 20.3% Black and 7.0% Hispanic individuals) comprising multiple years of data, integration of prescription dispensation data from Surescripts with clinical information,19,32 and inclusion of all patients who received the medication, whether or not they achieved persistent coverage. Patients who received their medication for T2D in this study had significantly lower odds of achieving 10% or greater weight reduction at year 1, compared with those who received it for obesity, after controlling for relevant sociodemographic and clinical factors, including the GLP-1 RA agent, medication dosage, persistent coverage at 1 year, and baseline BMI. Our database did not capture patient- and clinician-related factors (such as discontinuation of the medication therapy due to inadequate blood glucose level control, weight reduction, adverse effects, or coverage issues),16,33 and these could not be examined in this study. No refills were given without a current weight and dose. Achieving a target weight is also proposed to measure the success of the weight loss program. To propose a novel method to declare the ideal or target weight which bridges the difference in body composition, bone structure and sex. To evaluate safety, efficacy, extent of weight loss with likely consequential health benefits. Overweight, non-obese patients also strongly desire to return to their normal adult weight. Many providers compare obesity to other chronic conditions, like high blood pressure.The composite of death from any cause including nonfatal myocardial infarction or nonfatal stroke occurred in 4.3% of the oral semaglutide group and 5.6% in the placebo group.You can lose weight without exercise, but it's harder to do.Overall, 80% of subjects taking oral semaglutide reported an occurrence of AE compared with 74% receiving liraglutide and 67% receiving placebo.There is currently no official time limit for how long you can take semaglutide, and clinical trials show that it’s safe and effective when used for multiple years.Oral semaglutide treatment improved the fasting lipid profile from baseline and reductions in total cholesterol were statistically significantly greater with the oral semaglutide 7-mg and 14-mg doses compared with placebo. Through The Peptide Report, I share what actually works so you can make informed decisions and build a healthier, more resilient body. I believe in data, smart protocols, and taking responsibility for your own health. I’m Joe Mars, and I’ve dedicated the past ten years to understanding peptide therapy, longevity, and how to optimize the body through practical, real-life testing. Additionally, a greater decrease in systolic blood pressure in the oral semaglutide group was seen with a decrease of 5 mmHg compared with 2 mmHg in the placebo group. Other outcomes that were evaluated were a significant decrease in BW in the oral semaglutide group than in the placebo group (Table 2). A first event of unstable angina resulting in hospitalization occurred in 0.7% of subjects taking oral semaglutide and 0.4% taking placebo, while events of heart failure resulting in hospitalization occurred in 1.3% and 1.5%, respectively. The composite of death from any cause including nonfatal myocardial infarction or nonfatal stroke occurred in 4.3% of the oral semaglutide group and 5.6% in the placebo group. Health care professionals use the Body Mass Index (BMI), a measure of your weight in relation to your height, to define overweight and obesity.If you’ve been doing the same exercises for a while, your body may have become accustomed to them.AND ("randomized controlled trial"Publication Type OR "clinical trial"Publication Type)These findings highlight the need for real-life withdrawal studies to identify the predictors of the rapidity and magnitude of weight gain and investigate the effect of continuing counselling and lifestyle modification on the trajectory of weight regain (21).The primary end point was percentage change in body weight, and confirmatory secondary end points were achievement of 10% or more, 15% or more, and 20% or more weight loss, assessed for semaglutide vs liraglutide at week 68.The majority of the research participants were females (81.0%) and of White ethnicity (76.1%).Subgroup analyses of BMI change revealed that semaglutide 1.0, 2.4, and 2.8 mg led to larger reductions than placebo and more significant with the increase of dose (Supplementary Table S5).The main strength of this observational study is that it is the first real-life study evaluating the effectiveness and safety of semaglutide for weight management in Europe.While its short-term safety is well established, additional research is needed to assess long-term risks, particularly concerning heart health outcomes and sustained weight management. The significant reduction in long-term use could impede semaglutide's future growth. Therefore, physicians must be aware of the safety and efficacy of each semaglutide brand. Ozempic injection offers not only glycemic control but also reduces the risk of cardiovascular events in patients with and without T2D. For instance, the Rybelsus tablet demonstrates efficacy in improving the glycemic index of patients with T2D. For instance, this treatment prevented macroalbuminuria onset, which is indicative of kidney disease.9 Weight loss of 5% to 10% of your starting body weight may help improve your health by lowering blood sugar, blood pressure, and triglyceride levels. When combined with lifestyle and behavior changes, including healthy eating and increased physical activity, prescription medications help some people lose weight and maintain weight loss. Ask your health care professional about lifestyle treatment programs for weight management that will work for you. If you are overweight or have obesity, you might be able to lose weight with a lifestyle program that changes your behaviors and improves your eating and physical activity habits. Your health care professional may prescribe a medication to treat your overweight or obesity if you are an adult with Data for this retrospective cohort study were obtained from the Cleveland Clinic electronic health record (EHR) in Ohio and Florida, including linked Surescripts pharmacy dispensation records,18 from January 1, 2015, to July 28, 2023. A total of 3389 patients (mean SD age, 50.4 12.2 years; 1835 54.7% female) were identified. Percentage weight change and categorical weight reduction of 10% or greater at 1 year. This retrospective cohort study used electronic health records from a large, integrated health system in Ohio and Florida. Dr Butsch reported advisory board fees from Novo Nordisk A/S and research funding from Eli Lilly and Co during the conduct of the study. Progress may slow down, but staying committed to your treatment plan and seeking support when needed will help you move past plateaus and continue toward your health goals. Instead, they signal that your body has reached a new balance, and adjustments may be needed to continue making progress. Your doctor can review your progress, check for underlying issues (like thyroid problems or hormonal changes), and help adjust your treatment plan if needed. It just means your body has reached a new balance, and different strategies may be needed to continue making progress. When assessed according to anatomical therapeutic chemical classification system codes, obesity pharmacotherapies were initiated or ongoing in the extension in two (0.9%) and three (3.0%) participants in the semaglutide and placebo arms, respectively.The safety outcomes considered the proportion of participants with adverse events (AEs), serious adverse events (SAEs), adverse events leading to discontinuation (DAEs), and specific side effects, such as hypoglycemia, nausea, and diarrhea.PCOS (Polycystic Ovarian Syndrome), a medical condition that results in hormonal imbalances, frequently leads to weight gain.Thinking about starting semaglutide for weight loss or already on your journey?AUC24,Day10 area under the plasma concentration–time curve from time zero to 24 h after the tenth dose, Cmax,Day10 maximum plasma concentration 0–24 h after the tenth dose, ESRD end-stage renal disease, h hour, t1/2 terminal half-life, tmax,Day10 time to reach Cmax,Day10At week 68, treatments (including lifestyle intervention) were discontinued.Specifically, if a patient received semaglutide or liraglutide with a brand name approved for obesity or a brand name approved for T2D but without a documented diagnosis of T2D (indicating off-label use for obesity),22 the indication was captured as for obesity; otherwise, the indication was for T2D.Results from the STEP 5 trial, testing semaglutide as an adjunct to behavioral interventions in adults with overweight or obesity, demonstrate sustained weight loss over a period of 104 weeks. 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. These findings suggest that the results of STEP trials can be extrapolated and generalized to routine clinical practice. 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. Meta-analyses evaluating the efficacy and safety between semaglutide and placebo in obese patients have been conducted previously. Compared with once-daily liraglutide, once-weekly subcutaneous semaglutide, a novel longer-acting GLP-1RA, was approved by the FDA for weight management in the United States on 4 June 2021 (Lau et al., 2015; Hall et al., 2018; Kushner et al., 2020; Singh et al., 2022). 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). The trial included 17,604 people who received either weekly Wegovy or dummy injections (placebo) for up to 5 years. The potential bias in the treatment comparisons was mitigated by the matched double-blind placebo controls, but this could have been further improved with a double-dummy approach. Second, dosing differences meant participants knew which active treatment they could potentially receive. A crossover trial with a washout period could clarify the reasons for, and effects of, the greater discontinuation rate with liraglutide. Bearing in mind that obesity is a chronic, progressive, relapsing disease (17), the optimal duration of semaglutide therapy for weight management remains to be determined and may need to be tailored to individual characteristics. Both reduction in weight and improvement in cardiometabolic parameters, such as HbA1c, blood pressure and lipid profile, reached a plateau after 60 weeks and were sustained with its continued use for another year (16). The unprecedented efficacy of semaglutide for weight loss has generated widespread publicity and led to global drug shortages. Efficacy Both semaglutide doses significantly decreased mean HbA1c and body weight as compared with placebo by 7 months. The plasma concentration of subcutaneous semaglutide exhibits dose-proportional increases with once-weekly administration; however, increased body weight has shown to decrease exposure. This article reviews clinical trials assessing semaglutide and offers clinical details to further understand its role as a glucose-lowering medication for patients with T2DM. Data Selection The weight loss on 25 mg was comparable to those reported at 50 mg in OASIS 1 and 2.4 mg subcutaneously weekly in STEP 1,” Garvey said during the presentation. At baseline, nearly half of trial participants had prediabetes, while the remainder had normoglycemia. Semaglutide dose was escalated to 25 mg over the course of 12 weeks and maintained for 52 weeks. Lifestyle interventions, comprising physical activity, reduced caloric ingestion, and behavioral therapy, have been the principal pillars in the management of obesity supported by pharmacotherapy and bariatric surgery 7,8,9. Nevertheless, the importance of nutritional support during substantial weight loss with pharmacotherapy needs to be re-evaluated. Lifestyle changes, including physical activity, reduced caloric ingestion, and behavioral therapy, have been the principal pillars in the management of obesity. Since starting Wegovy®, I've lost about 50 pounds over two years, and that's about 17% of my starting body weight. I was nervous about how the weight was affecting my body overall. Let's explore what science tells us about the first month on semaglutide and what you can realistically expect when you start. But having realistic expectations based on solid research – not social media anecdotes – can help you stay motivated and stick with your treatment plan. Individual participant data will be shared in data sets in a de‐identified and anonymized format. TKO contributed to the data analysis and interpretation and manuscript development. KKo contributed to the data analysis and interpretation and manuscript development. The treatment was administered as an adjunct to a low-calorie diet for the first 8 weeks, followed by 60 weeks of intensive behavioural therapy including a hypocaloric diet and increased physical activity. GI adverse events (mostly mild to moderate) were reported by 64% of participants in the 2.4 mg semaglutide group, 58% in the 1.0 mg semaglutide group and 34% in the placebo group.52 Once-weekly subcutaneous 2.4 mg semaglutide (Wegovy™; Novo Nordisk A/S, Bagsværd, Denmark) is the newest medication approved for chronic weight management. Rather, it should be treated like other chronic cardiometabolic conditions such as T2D, hypertension and hyper- or dyslipidaemia, with treatment aiming to disrupt long-term acquired biochemical circuits.21,22 Losing weight and maintaining weight loss over the long term will always be a challenge. Given the complex pathophysiology of obesity and the potent counterregulatory neuroendocrine pathways activated to counter weight loss, obesity can no longer be attributed to a lack of willpower. Data from clinical trials on FDA-approved medications should NOT be used to make assessments related to compounded medications. No, semaglutide doses are increased gradually to reduce the risk of side effects like nausea. Semaglutide can begin lowering blood sugar levels within the first week, with continued improvement over several weeks as the dose is adjusted. Injection site reactions were reported in only four participants in the semaglutide 2.4 mg arm. Gastrointestinal-related symptoms, which were mostly mild to moderate, were more common in semaglutide 1.7 mg group (64%) than semaglutide 2.4 mg group (59%) or placebo group (30%). The rate of drug termination was higher in semaglutide groups (3%) compared to placebo (1%). Unexpectedly, the percentage of serious adverse events was lower in the semaglutide 2.4 mg arm (5%) contrasted with semaglutide 1.7 mg and placebo arms (7% each). The rate of reported adverse events was 86% in the semaglutide 2.4 mg group, 82% in the semaglutide 1.7 mg group, and 79% in the placebo group. No incidence of infection was observed with the use of multi-dose vials. Anecdotally, more patients who requested Zofran were under 30 years old and seemed to want it ‘on hand’ when they were out drinking alcohol. 18.5% (60/326) of patients requested Zofran. The change in the amount of weight, in pounds, and 1.5% (5/326) gained weight, and 2.1% (7/326) did not lose weight. A handful of preclinical studies showed that GLP-1RAs induce pancreatic inflammation, cellular proliferation and intra-epithelial neoplasia (PanIN) (70–72). While establishing (the absence of) a link with pancreatitis and pancreatic cancer in large clinical studies was one aspect in this field of research, others focused on animal studies and more mechanistic findings. When combining all available CVOT data (including those from non-semaglutide GLP-1RAs) in a meta-analysis, a hazard ratio of 1.05 (95% confidence interval CI 0.78–1.40) was found for pancreatitis and 1.12 (95% CI 0.77–1.63) for pancreatic cancer (63). In the subsequent years, many pharmacovigilance and database studies followed, with conflicting results (54–60). An effect on the central nervous system has been suggested as a recent study with modified exenatide—with reduced brain penetrance—showed less vomiting in musk shrews, despite retaining effects on glucose control (46).