This had the effect of increasing the percentage of firms for whom contact was made from whom we collected offer rate information. Since 2014, we have collected offer rate information from firms before a final disposition is assigned. Changes in both the survey methodology and the health insurance market have led us to become increasingly cautious about assuming that the follow back survey is a suitable proxy for the true population. Looking at the decade from 2010 to 2019, offer rates among firms responding to the follow-up survey have been higher for five of ten surveys. The adjustment involves comparing the distribution of offering to non-offering firms in the full survey and the follow-back sample in the three smallest size categories (3-9, 10-24, 25-49). Most patients lose approximately 1-2% of their baseline body weight during the first month, which typically translates to 2 to 5 pounds, though individual results vary considerably. According to US obesity treatment guidelines, continuation of therapy should be reassessed if a patient has not lost at least 5% of baseline weight after approximately 3 months on the maintenance dose. According to US obesity treatment guidelines, clinicians should consider whether to continue therapy if a patient has not lost at least 5% of baseline weight after approximately 3 months on the maintenance dose. Data from the STEP trials demonstrate that weight loss often increases as the dose increases, with significant reductions typically occurring between months 2 and 6 of treatment. A third of these firms were sent a $5 Starbucks gift card in the advance letter, a third were offered an incentive of $50 in cash or as a donation to a charity of their choice after completing the full survey, and a third of firms were offered no incentive at all.No retrospective cohort study has assessed the effectiveness of semaglutide at doses used in randomized clinical trials to treat obesity (ie, 1.7 and 2.4 mg).Slight heterogeneities in RBW change and 5% weight loss were yielded after deleting any of the studies.Although the benefits of semaglutide are well documented, newer medications, such as tirzepatide, have shown potentially greater weight reduction effects, highlighting the need for direct comparative studies.In order to improve statistical power among sub-groups, including small firms and those with a high share of low income workers, the size of the sample was expanded from 5,732 in 2016 to 7,895 in 2017.The study found that once daily, subcutaneous semaglutide achieved superior weight loss compared to placebo and liraglutide in patients with obesity but without type 2 diabetes .These combined actions lead to reduced energy intake and subsequent weight loss. The primary analysis focused on the mean percentage change in body weight in each subgroup (DM vs. non-DM). By quantifying differences in treatment response based on diabetes status, this analysis aimed to provide evidence to support precision treatment approaches in obesity management. Although semaglutide promotes weight loss in both diabetic and non-diabetic populations, studies have consistently shown a tendency toward reduced weight loss in individuals with DM compared with those without DM . For individuals with obesity, weight loss offers multiple clinical benefits, including improved glycemic control, enhanced insulin sensitivity, and reduced cardiovascular risk 4,5. While once-weekly semaglutide at 2.4 mg elicited significant weight loss in both populations, the magnitude of effect was notably greater in those without DM. Our aim was to identify randomized controlled trials (RCTs) that compared the efficacy of semaglutide administered once weekly with placebo in overweight or obese adults. Adverse events leading to discontinuation occurred in 7% of the oral semaglutide group vs. 6% of the placebo group.Wharton and colleagues write that "oral semaglutide at a dose of 25 mg may enhance the flexibility of the treatment strategy for overweight and obesity by providing an alternative dose for the oral molecule as well as an alternative to subcutaneous semaglutide at a dose of 2.4 mg." Seventy percent of patients who had prediabetes or diabetes before treatment became normoglycemic (no longer had prediabetes or diabetes) after 24 months 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. Experts are concerned that, in some cases, the side effects of prescription medications that treat overweight and obesity may outweigh the benefits. Medications don’t replace physical activity or healthy eating habits as a way to lose weight. 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. Prescription medications to treat overweight and obesity work in different ways. If you are struggling with your weight, a healthy eating plan and regular physical activity may help you lose weight and keep it off over the long term. This meta-analysis aimed to assess the efficacy and safety of once-weekly semaglutide among adults with overweight or obesity. Importantly, clinical trials investigating weight loss typically involve more intensive follow-up and support for patients, which may enhance adherence and outcomes compared with routine clinical practice . Most patients in both cohorts achieved clinically meaningful weight loss over 1 year, with 84.1% in the semaglutide 2.4 mg cohort and 86.2% in the tirzepatide cohort achieving weight loss of ≥ 5% (Table 3). The proportion of patients in each treatment cohort who achieved clinically relevant weight loss (i.e., ≥ 5% ) was then evaluated. The estimated mean changes in HbA1c from baseline to Week 44 were −0.8% and −0.1% with semaglutide 2.4 mg and placebo, respectively (ETD −0.7%; 95% CI −0.8, −0.5; p p 2). Mean BMI changes from baseline at Week 44 were −4.0 kg/m2 and −1.2 kg/m2 with semaglutide 2.4 mg and placebo, respectively (ETD –2.8 kg/m2; 95% CI –3.5, −2.0; p 2). Week 44 responses were analysed using an analysis of covariance model with randomized treatment and T2D status as factors and baseline fasting serum insulin/baseline lipid value as covariates. Overall, mean (standard deviation SD) body weight was 96.4 kg (17.4), mean waist circumference was 107.5 cm (11.1) and mean BMI was 33.8 kg/m2 (4.6). Two estimands (treatment policy estimand and trial product estimand; supplementary materials p5) were used to assess treatment efficacy and accounted differently for intercurrent events and missing data, as described previously.11, 12 Based on data from the STEP trials, once‐weekly subcutaneous semaglutide 2.4 mg has been approved in Canada, Europe, the UK and the USA for chronic weight management in adults with overweight (with weight‐related comorbidities) or obesity.20, 21, 22, 23 In STEP 5, mean weight loss was −15.2% with semaglutide 2.4 mg versus −2.6% with placebo from baseline to week 104. The Semaglutide Treatment Effect in People with obesity (STEP) clinical trial programme is evaluating once‐weekly subcutaneous semaglutide 2.4 mg (a glucagon‐like peptide‐1 analogue) in people with overweight or obesity. In conclusion, semaglutide is efficacious for sustained weight loss in patients with overweight/obesity and without diabetes. Our objective was to examine the long-term efficacy and safety of semaglutide use for weight loss in patients with overweight/obesity and without diabetes. In comparison to other available AOMs, semaglutide shows a considerable enhancement in efficacy, being the first medication safely producing a greater than 10% average weight loss over that attributable to lifestyle interventions (12). 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. Six of the program trials (STEP 1–4, 6, and 8) were published; the STEP 5 trial has been completed but not yet published, and the remining trials, including STEP 7, have not been completed yet. Mechanistically, semaglutide is an incretin, which blocks glucagon release, postpones gastric clearing, reduces energy intake, stimulates satiety, and reduces hunger and appetite via peripheral and central nervous system actions . 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. Obesity is a complex and chronic disease and has a wide array of complications, including hypertension, hypercholesteremia, type 2 diabetes, cardiovascular disease, and some cancers 1,2,3,4,5,6. All the STEP studies included diet and exercise interventions but at different intensities. Patients in STEP 1 were desirous of weight loss as a reason for study participation and received structured lifestyle intervention (which included a −500 kcal per day diet with 150 min per week of physical activity).Three semaglutide-treated patients had a gastric band in situ, inserted between 2007 and 2009, showing a three-month weight loss of 2.7 kg (2.4%), 6 kg (5.6%), and 7 kg (6.0%) and experiencing in two cases mild and in one case moderate side effects.By quantifying differences in treatment response based on diabetes status, this analysis aimed to provide evidence to support precision treatment approaches in obesity management.Because semaglutide may influence the rate of gastricemptying, the absorption of concomitantly administered oral medications may be delayed.13 There was no apparent effect on the rate of gastric emptying observed duringthe paracetamol absorption test with semaglutide 2.4 mg.38 Two studies showed no clinically significant pharmacokinetic or dynamicimpacts on warfarin, digoxin, atorvastatin, or metformin when taken withsubcutaneous semaglutide 1.0 mg or oral semaglutide 20 mg.39,40 Further studies should beconsidered to evaluate semaglutide 2.4 mg on narrow therapeutic index drugs.Sponsorship for this study was funded by Novo Nordisk Inc. (Plainsboro, NJ, USA).Of the trials included in the SLR, 108 RCTs (164 publications) investigated non-surgical interventions.Both Ozempic and Wegovy contain the active ingredient semaglutide, but only Wegovy is formally indicated for weight loss while Ozempic is FDA-approved to treat type 2 diabetes. During this period, the combined effects of weight loss, improved metabolic health and established healthy habits often create momentum that helps maintain long-term success. These initial effects don’t usually translate to significant weight loss yet, as your body is still adjusting to the medication. Most patients start experiencing appetite changes within the first week of treatment. Serious adverse events were reported in 2.3% of participants during the run-in period (eTable 8 in Supplement 1) and in 7.7% and 5.6% receiving continued semaglutide and placebo, respectively (Table 3). In-trial observation period data (time from randomization to last contact with trial site, irrespective of treatment discontinuation or rescue intervention). Further supportive secondary end point analyses, including absolute body weight changes, are reported in Table 2 and eTable 5 in Supplement 1. The SF-36 physical functioning scores significantly improved with continued semaglutide vs placebo from week 20 to week 68 (P Table 2; eTable 5, eFigure 6, and eFigure 7 in Supplement 1). Therefore, an efficacy-effectiveness gap does not exist with respect to semaglutide in weight management, supporting the generalizability of RCT findings . The semaglutide discontinuation rate due to adverse events was 2.5%, with only one patient discontinuing semaglutide after seven weeks due to persistent vomiting and acute abdominal pain. Severe adverse events were noted only in three patients (7.5%), with vomiting resolved in two cases within four weeks. Of note, most patients (six out of nine) had depression, two anxiety, and one bipolar disorder, with the use of psychotropic medications, mostly selective serotonin reuptake inhibitors, being recorded at the time of study enrollment in seven individuals. Patients with psychiatric disorders were overrepresented in the non-responders group, with four out of nine patients (44.4%) not showing favorable responses to semaglutide therapy. Semaglutide also substantially improved physical function scores compared to the placebo assessed by the 36-item Short Form Health Survey (SF-36) and the Impact of Weight on Quality of Life–Lite Clinical Trials Version (IWQOL-Lite-CT) questionnaire. The majority of the participants were females (74.1%) and of White ethnicity (75.1%). The average age and BMI of the participants were 46 years and 37.9 kg/m2, respectively. Percent Weight CFB to 52 Weeks Among firms that offer health benefits with 200 or more workers, 16% of firms with 200 to 999 workers, 30% of firms with 1,000 to 4,999 workers, and 43% of firms with 5,000 or more workers cover GLP-1 agonists when used primarily for weight loss in 2025. Nutrition recommendations for a healthy pregnancy and lactation in women with overweight and obesity – strategies for weight loss before and after pregnancy. You can manage your health in pregnancy without weight loss medications by following the steps below. In healthy non-pregnant adults, it can take 5 to 7 weeks on average for semaglutide to leave your body. During the 20-week run-in, mean body weight declined by 10.6% to 96.1 kg (Table 1). AThese participants received once-weekly semaglutide (safety analysis set). The tertiary estimand was identical to the primary treatment policy estimand, and the quaternary estimand was identical to the secondary trial product estimand, except values at week 20 (baseline) were replaced by those at week 0 (start of run-in) in the respective analyses. The tertiary estimand was identical to the primary treatment policy estimand, and the quaternary estimand was identical to the secondary trial product estimand, except values at week 20 (baseline) were replaced by those at week 0 (start of run-in) in the respective analyses.Results are reported for the treatment policy estimand unless stated otherwise. The present study examined individuals that were prescribed semaglutide to analyze its overall effect on weight loss and determine the impact of relevant clinical factors on this loss. Three healthcare systems did not have adequate information or data conformance for semaglutide patients that met the study criteria and were excluded; as a result 10 health systems with observations from March 2017 to April 2022 were used. Additionally, after 52 weeks, up to 65% of patients lost at least 10% in body weight (6). Machine learning analysis of electronic health record data identified factors that warrant further research and consideration when tailoring weight loss therapy. This dose was selected based on a phase 2 clinical trial in which greater weight loss was achieved with once-daily semaglutide, 0.4 mg (equal to 2.8 mg weekly), than with placebo or liraglutide 3.0 mg/day.(25) It is available in single-use, prefilled pens. Subjects achieving ≥5% and ≥10% weight loss were analyzed using a logistic regression model with treatment versus subgroup interaction and baseline body weight as covariate with missing data imputed from the corresponding mixed model for repeated measurements for change from baseline. To assess the effect of baseline body mass index (BMI) and the occurrence of nausea and/or vomiting on weight loss induced by semalgutide, a once‐weekly glucagon‐like peptide 1 analogue for the treatment of type 2 diabetes. Although a higher maintenance dosage of semaglutide (2.4 mg/wk) was used in this trial, the adverse event profile and tolerability were consistent with data from a phase 2 study in people with obesity14 and semaglutide trials in patients with type 2 diabetes using lower maintenance dosages (up to 1.0 mg/wk),34 as well as with that reported for other GLP-1 receptor agonists,35 with no new concerns. Nausea is the most frequently reported side effect, especially during the first few weeks. While semaglutide is generally well-tolerated, some users may experience side effects. Reducing processed foods and sugary drinks helps maximize semaglutide’s appetite-suppressing effects. While semaglutide is effective, your results can vary based on several key factors. The current analysis of construct validity of the Sim-Q used only the treatment satisfaction scale, which is derived from six of the items.Semaglutide, a GLP-1 receptor agonist, was initially approved in December 2017 as anadjunct to diet and exercise for the management of type 2 diabetes at doses up to 1mg weekly.As illustrated by the gray shading, the week 104 bars present results at this time point among the subgroups of participants with baseline prediabetes (a and b) or baseline normoglycemia (c and d).In 2016, more than 1.9 billion adults older than 18 years were over-weight and 650 million were obese.2 Treatment options for obesity include bariatric surgery and nonsurgical treatment such as diet modification, behavioral therapy and pharmacologic therapy.5COVID-19 infection was reported by 16 (10.5%) of 152 participants in the semaglutide group versus eight (5.3%) of 152 participants in the placebo group, with very few cases in each group classed as serious and none requiring temporary or permanent interruption of semaglutide treatment.But how long can you take semaglutide without your weight loss stalling?We then discontinued semaglutide; weight loss was maintained for 6 months.A few months later, the FDA approved semaglutide, under the brand name Wegovy, as a weight-loss therapy for people who were overweight or obese.Individuals on semaglutide experienced weight loss success, and the weight loss at different exposure durations are shown in Table 2. Change in body weight from baseline was estimated from a mixed model for repeated measurements with treatment and baseline BMI subgroup as fixed factors, interaction between treatment and BMI subgroup at baseline and baseline body weight as covariate, all nested within visit. Furthermore, it is not known whether baseline body mass index (BMI) affects the degree of semaglutide‐induced weight loss. Change from baseline in body weight was assessed within each trial and subgroup. Subjects with inadequately controlled type 2 diabetes (drug‐naïve or on background treatment) were randomized to subcutaneous semaglutide 0.5 mg (excluding SUSTAIN 3), 1.0 mg (all trials), or comparator (placebo, sitagliptin, exenatide extended release or insulin glargine). Semaglutide injection 2.4 mg (Wegovy®; hereafter referred to as semaglutide) was approved by the US Food and Drug Administration in June 2021 for chronic weight management in adults with overweight or obesity.For retirees with Medicare coverage, retiree health benefits can provide an important supplement to Medicare, helping them pay for cost sharing and benefits not otherwise covered by Medicare.Importantly, semaglutide did not lead to an increased rate of pancreatitis, but rates of cholelithiasis (stones in gallbladder) were higher in the semaglutide group.Both employers that offer and those that do not offer health benefits were asked if they provide funds to any employee to purchase non-group coverage.FCOVID-19 adverse events were classed as serious in one participant in the semaglutide group and in two participants in the placebo group; none required permanent discontinuation of the trial product.Content validity of the Sim-Q has been supported by qualitative research with patients .A similar proportion of participants had T2D at screening between the treatment groups (semaglutide 2.4 mg 26.7% vs. placebo 24.8%). The Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) 2020 Guidelines 14-15 are standard for systematic reviews and were used to conduct and record the data presented in this systematic review. Lifestyle interventions and dietary modifications are the initial approaches to weight reduction . Reduction in BMI decreases the risk of development of type 2 diabetes mellitus, hypertension, acanthosis nigricans, and depression to name a few 3-6. If you’re not trying to get pregnant, this is one of the easiest ways to reduce the chance of a surprise pregnancy while you’re on treatment. Many female patients also pursue an IUD. That’s why labels recommend using a non-oral contraceptive method or adding a barrier method for 4 weeks after initiation and 4 weeks after each dose escalation. Medications that support weight reduction and insulin sensitivity may also change menstrual cycles for some women. Because human pregnancy safety data is limited, the standard approach is to reduce “avoidable exposure” during that early window. Semaglutide 2.4 mg is not included in current obesity guidelines by the AmericanAssociation of Clinical Endocrinologists (AACE) and the American Heart Association,American College of Cardiology, and The Obesity Society (AHA/ACC/TOS), which werepublished in 2016 and 2013, respectively.4,5 In the AHA/ACC/TOS guidelines,there is limited mention of pharmacotherapy due to a paucity of FDA-approvedmedications at the time of development. In addition to a strong efficacy and safety profile,once-weekly therapy has the potential to improve adherence over daily therapy. In humans, it is unknownwhether semaglutide causes thyroid C-cell tumors, including MTC. Comparison of Efficacy, Side Effects, Contraindications, and Significant DrugInteractions for Common Antiobesity Medications. In those who continued semaglutide after randomization, weight loss achieved during the run-in period not only was sustained but continued, reaching a plateau at week 60 to week 68 and ultimately resulting in an estimated reduction of 17.4% over the entire trial. ETable 5 in Supplement 1 shows corresponding data for the trial product estimand (which assessed the treatment effect assuming participants continued taking randomized treatment for the planned study duration without rescue intervention). ETable 5 in Supplement 1 shows corresponding data for the trial product estimand (which assessed the treatment effect assuming participants continued taking randomized treatment for the planned study duration without rescue intervention).bData are absolute differences between estimated mean changes unless stated otherwise. The first month involves a low starting dose (0.25 mg weekly) designed to minimize gastrointestinal side effects and allow the body to adapt to the medication. Patients should not use semaglutide with other GLP-1 receptor agonists, and safety with other weight-loss medications has not been established. Regular physical activity, including both aerobic exercise and resistance training, improves body composition and metabolic health. Those scheduled for procedures requiring anesthesia should inform their healthcare team about semaglutide use due to its effects on gastric emptying. Some patients report improved energy levels as dietary patterns stabilize and blood glucose levels (in those with prediabetes or diabetes) improve. Your Individual Body Response Our findings are consistent with the current literature surrounding semaglutide's effectiveness in achieving greater weight loss, improving or resolving obesity‐related comorbidities, and reducing food noise and disordered eating patterns 6, 7. One prominent finding from our analysis highlights the effectiveness of semaglutide 2.4 mg in facilitating substantial weight loss among users of the medication. The analysis of data collected from the subreddit “r/WegovyWeightLoss” provides valuable insights into the experiences of individuals using semaglutide 2.4 mg for weight management. Users consistently reported slow but sustainable weight loss with semaglutide 2.4 mg, with some achieving milestones such as reaching healthy BMI ranges or losing substantial amounts of weight. BMI is a good surveillance measure for population changes over time, given its strong correlation with body fat amount on a population level, but it may not accurately indicate the amount or location of body fat at the individual level2. Iqbal et al. (2022) and Zhong et al. (2022) designed the study in non-diabetic patients intriguingly, but only contained three or four RCTs about semaglutide and placebo. Continued use of semaglutide, along with healthy routines, can help maintain weight loss and prevent regain. On average, you may see around 5–6% of body weight loss by this point. The recommended duration of semaglutide use for weight loss is usually around 12 to 24 months—but it can vary depending on your personal journey. Several factors may explain the differences observed between real-world and clinical trial weight loss outcomes. Lastly, a retrospective cohort study compared post-treatment outcomes for semaglutide and tirzepatide in a population of patients without T2DM. Results are presented visually by treatment cohort and T2DM status at 12 months in this study, but data points and sample sizes are not stated, preventing interpretation and comparison of outcomes with those from the current study . Additionally, the high prevalence and generally similar obesity-related complications in both cohorts suggest consistent clinical profiles of the patients who received these treatments. All-cause HCRU and medical costs over the follow-up period were also compared post IPTW, as well as changes in weight and HbA1c. Standardized mean difference (SMD) was reported as a measure of balance for baseline characteristics and HCRU/cost both pre and post IPTW. In addition, composite outcomes were assessed in terms of the proportion of patients achieving both follow-up HbA1c Change in HbA1c was evaluated by subtracting the baseline value from the follow-up value. The proportion of patients with obesity (BMI ≥30 kg m−2) fell from 71.0% to 43.3% in the semaglutide group versus 71.9% to 67.9% in the placebo group. 4, which depicts in-trial patients receiving semaglutide and placebo. At week 104, 52.4% of patients treated with semaglutide achieved improvement in BMI category compared with 15.7% of those receiving placebo. Semaglutide is a glucagon-like peptide-1 (GLP-1) analog approved for the treatment of type 2 diabetes (oral semaglutide and subcutaneous semaglutide) and for reducing the risk of cardiovascular events in people with type 2 diabetes and cardiovascular disease (subcutaneous semaglutide only)2,3,4,5. Behavioral intervention incorporating modifications in diet and physical activity remains the foundation of treatment for overweight and obesity. Most participants were female (236 (77.6%)) and white (283 (93.1%)), with a mean (s.d.) age of 47.3 (11.0) years, body mass index of 38.5 (6.9) kg m–2 and weight of 106.0 (22.0) kg. Demographic and clinical characteristics were generally descriptively similar between the cohorts (Tables 1, 2). Novo Nordisk Inc. has a data access license to the Komodo Health database. This study was conducted in accordance with relevant guidelines and regulations, including the principals of the Declaration of Helsinki of 1964 and its later amendments. The STEP 1 Trial In developing semaglutide, prioritizing the fatty acid moiety and linking chemistry was crucial for achieving high albumin affinity and GLP-1 receptor (GLP-1R) potency, enabling prolonged exposure of the GLP-1 analogue. This research article focuses on understanding the mechanism and forms of semaglutide therapy, efficacy, contraindications, any adverse effects and common drug interactions. Its pharmacological profile is characterized by high affinity and specificity for the GLP-1 receptor, coupled with a prolonged half-life of about one week due to albumin binding . Moreover, the intricate relationship between T2DM and obesity contributes to a state of chronic low-grade inflammation and insulin resistance, further exacerbating metabolic dysfunction 1, 5. Cardiovascular morbidity and mortality are significantly elevated in T2DM patients, with a two-to-four-fold increased risk of adverse cardiovascular events compared to non-diabetic individuals 1, 3, 4. We performed a post hoc analysis of patients with or without type 2 diabetes and of patients receiving different doses of semaglutide. The study included 175 patients (132 women 75.4%; mean SD age, 49.3 12.5 years; mean SD BMI, 41.3 9.1) in the analysis at 3 months and 102 patients at 6 months. Third, pooled placebo data from participants receiving different background therapies or lower-dose arms in some studies 22,25 may introduce bias and influence comparisons. The development of a high-dose (50 mg) oral formulation of semaglutide, as investigated in the OASIS 1 trial , has shown weight loss results comparable to those achieved with the subcutaneous 2.4 mg dose. Beyond its effects on body weight and glycemic control, semaglutide has demonstrated significant cardiovascular benefits. Shu et al. 2022 found severe gastrointestinal adverse events (AEs) related to semaglutide treatment were reported in 1,778 GI cases and 3,601 overall cases, resulting in 40 (2.25%) and 102 (2.83%) deaths, respectively . Another retrospective chart review found a significant association between semaglutide therapy and RGC in patients that underwent elective esophagogastroduodenoscopy . Additionally, an increased risk of malformations was noted for liraglutide and semaglutide at doses similar to those used in human treatments . Product labeling indicates that animal studies have suggested a potential for reproductive toxicity at maternally toxic doses for semaglutide, dulaglutide, exenatide, and liraglutide. In one such case, a 40-year-old female exposed to semaglutide Ozempic had a child with an atrial septal defect that resolved spontaneously 3 years after birth . Some workers in health plans with high deductibles also receive contributions to savings accounts from their employers. Over half (53%) of covered workers in firms with 10 to 199 workers are in such a plan, compared with 28% of covered workers in larger firms. The average deductible for covered workers at firms with 10 to 199 workers ($2,631) is higher than the average deductible at larger firms ($1,670). These plans have the potential to meaningfully affect competition in the small group market because, unlike insured plans, they use health status in rating and underwriting, and are not required to provide all of the essential health benefits that are mandatory for insured plans. Thirty-seven percent of covered workers in firms with 10 to 199 workers are covered by a level-funded plan, similar to the percentage in 2024. It is used to manage gestational diabetes, weight gain, prevent T2DM and treat polycystic ovarian syndrome . However, future studies should follow patients longitudinally to see how these effects persist long term. In a study reviewing the FDA Adverse Event Reporting System, primary treatment for acute gallbladder injury was a cholecystectomy, performed in 30 out of 36 cases. Secondary outcomes (changes in SBP, DBP, HbA1c, LDL-C, HDL-C, and triglycerides) were assessed from baseline (– 90 days to index date) to 12 months (365 days ± 90 days). Patient demographic and clinical characteristics, including relevant comorbidities, as well as procedures and medications, were evaluated during the baseline period. Because this study used only de-identified data compliant with the requirements of the Health Insurance Portability and Accountability Act, Institutional Review Board review and approval were not needed. Patients were excluded if, in the baseline period, weight ≥ 181 kg, latest BMI 2, or no weight/BMI value was available (Supplemental Table 1 provides additional exclusion criteria details). In chronic diseases with multiple treatment options, the patient’s perspective of treatment simplicity could help differentiate between treatment options with similar effectiveness. However, the sample’s clinical and geographic diversity may help mitigate this limitation to some degree. A limitation of this study is that generalizability of results to countries other than the USA is unknown. Therefore, it may be useful to assess and quantify treatment simplicity across various medical conditions, and the approach used for the Sim-Q could apply to other medical conditions. Treatment simplicity may be particularly important in differentiating between treatments for chronic diseases that have similar effectiveness. 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. In published data from the STEPprogram, patients treated with semaglutide 2.4 mg consistently achieved clinicallymeaningful weight loss compared to both placebo and liraglutide.16-21 Despite the lack ofhead-to-head trials, semaglutide 2.4 mg documented safety and efficacy for periodsup to 2 years establishes it as a top option for weight management when combinedwith lifestyle changes. However,only doses of 0.2 mg or more showed statistically greater mean weight loss whencompared to liraglutide 3.0 mg (-7.8%).23 In the STEP program, STEP 8 confirmed the results of this phase 2 trial.Adult patients who were obese or overweight with at least one weight-relatedcomorbidity and without diabetes were randomized to either weekly semaglutide 2.4mg, daily liraglutide 3.0 mg, or a matching placebo. Across the phase 3 trial program for type 2 diabetes (SUSTAIN),semaglutide consistently demonstrated clinically significant weight loss (up to -6.5kg with 1.0 mg semaglutide).6-12 Subsequently, semaglutide hasbeen approved at a higher dose, 2.4 mg, as an adjunct to a reduced-calorie diet andincreased physical activity for chronic weight management in patients who haveobesity, or are overweight with at least one other weight-related comorbid condition.13 This article reviews clinical trials assessing the efficacy and safety ofsemaglutide at a dose of 2.4 mg for chronic weight management. An increasing number of studies and clinical trials investigating semaglutide-based medications have aimed to confirm the effect of the drug on weight loss and its effectiveness as an obesity treatment in adults. How should you manage your health (without weight loss medication)? The mean pulse rate increased significantly with oral semaglutide 14 mg but not with 3 or 7 mg in Pioneer 1 Trial as well as 2-4 beats increase in pulse rate in the pioneer 8 trial 13, 20. Step 1 trial extension conducted by Wilding et al. included 327 participants. Rodbard et al. conducted Pioneer 2 Trial, to compare the efficacy and safety of oral semaglutide to empagliflozin in type 2 diabetes mellitus (T2DM) uncontrolled with metformin alone . We included 12 randomized controlled trials (RCTs) in our study. Then, two authors (Mahvish and Shrinkhala) assessed the data independently and filtered for all studies that were identified. Introduction Recent randomized controlled trials (RCTs) have shown the great efficacy of semaglutide in achieving significant weight loss in overweight and obese adults. Our data are also consistent with other recent real-world observational studies of semaglutide OW where weight reductions of 2.8–7.8 kg have been reported, together with HbA1c reductions of 0.8–1.5% 21–31. This provides evidence for the utilization of GLP-1 RAs over SGLT2i in patients with T2D to help achieve real-world optimal glycemic control, as well as reductions in body weight. Childhood obesity often predicts adult obesity, highlighting the need for early intervention. Genetic factors contribute significantly to obesity risk, accounting for 40-70%, but their expression is greatly influenced by environmental and behavioral factors 2,4. The obesity epidemic involves a complex interplay between modifiable and non-modifiable risk factors that affect countries globally at various developmental stages. The dual primary end points were change from baseline in the Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS), used to assess HF-related symptoms and physical limitations, and change in body weight. In a study published in the journal Nature, 68 percent of participants taking semaglutide achieved 5 percent or more weight loss and 44 percent achieved 10 percent weight loss after two years. To establish a more definitive relationship between HT use and weight loss response to semaglutide in postmenopausal women, future prospective studies should incorporate the age at menopause; type of menopause; the duration, type, and dose of HT use; data on sleep quality, vasomotor symptoms, quality of life, activity, diet, and allostatic load; and the timing of semaglutide initiation in relation to HT initiation. A relatively low HbA1c level at the time of initiation of oral semaglutide was reported recently by Candido et al. but, in such study, most patients were switching from a regimen containing DPP-4 inhibitors . However, it should be noted that baseline HbA1c was lower (7.2%) in those who subsequently discontinued oral semaglutide, possibly suggesting that the drug was being used not only for glucose control, but also for weight management. An analysis of German data showed a median persistence time of 11 months, with a trend increase from the 2007–2012 to the 2017–2020 period . Among patients who discontinued treatment 47.5% did not achieve a reduction of HbA1c compared to baseline. Serious adverse events were reported by 12 (7.9%) of 152 participants in the semaglutide group and 18 (11.8%) of 152 participants in the placebo group (Table 3). Gastrointestinal disorders, namely nausea, diarrhea, vomiting and constipation, were the most frequently reported adverse events and occurred in more participants treated with semaglutide than with placebo (125 (82.2%) of 152 versus 82 (53.9%) of 152, respectively) (Table 3). The achievement of at least 5% weight loss analysis was conducted with the use of logistic regression, with the same factor and covariate. As statistical superiority for both co-primary endpoints was demonstrated for semaglutide versus placebo, the prespecified criteria for a positive trial were met, indicating a significant benefit of semaglutide versus placebo. Mean body weight was 106.0 kg and mean BMI was 38.5 kg m–2. The study, published in the Annals of Internal Medicine, found that semaglutide significantly increased weight loss but also caused gastrointestinal disorders in participants. It found that semaglutide treatment improves weight-related quality of life significantly more than placebo, along with improvements in control of eating and body composition. The study reported substantial, sustained weight loss and a higher percentage of participants achieving ≥5% weight loss with semaglutide. 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.In this real-world comparative effectiveness study, patients treated with semaglutide 2.4 mg had greater percentage and absolute reductions in weight at 12 months than non-treated patients.For this reason, never take a weight management medication only to improve the way you look.Information offered by SemaglutideMedics.org is for educational purposes only, not medical advice, diagnosis, or treatment.Additional information about the study data can be obtained from the corresponding author upon reasonable request.Baseline characteristics were broadly similar between subjects across treatment groups (Table 1), with differences between trials reflecting the eligibility criteria.The FDA received 605 adverse event reports for compounded semaglutide and 545 reports for compounded tirzepatide as of July 2025.Moreover, the sensitivity analysis was assessed to evaluate the stability and reliability of the results.Future studies should focus on extended comparative analyses of semaglutide and emerging obesity treatments to determine their relative effectiveness, safety, and patient adherence trends. Importantly, studies suggest that significant weight loss is largely independent of the occurrence of these gastrointestinal side effects . These findings suggest that the cardiovascular protection offered by semaglutide may extend beyond glucose lowering and weight loss, potentially involving direct effects on atherosclerosis, inflammation, and endothelial function 41,42. As glycaemia normalizes, this route of caloric loss is reduced, potentially offsetting part of the energy deficit induced by semaglutide and attenuating overall weight loss . The presence of DM appears to attenuate the weight loss response to semaglutide. To our knowledge, this is among the first meta-analyses to provide a systematic and quantitative comparison of the weight-lowering efficacy of once-weekly subcutaneous semaglutide at 2.4 mg between individuals with and without DM. Fat accumulation beyond healthy limits eventually leads to several cardiovascular complications, including hypertension, heart failure, ischemic heart disease, and stroke.2–5 Specifically, the metabolic profile is hugely affected by obesity, including hyperinsulinemia, dyslipidemia, impaired fasting glucose, or hypercholesterolemia.6–8 The severity of obesity increases with continuous weight gain and tends to have higher all-cause mortality and mortality due to a wide range of other serious health complications. As to be expected with a GLP-1 receptor agonist, about half of patients who continued on semaglutide experienced gastrointestinal adverse events versus about 26% of those on placebo. Following this, 535 participants – who already achieved their target maintenance dose of 2.4 mg weekly – were randomised to continue on their 2.4-mg-per-week dose of semaglutide for an additional 48 weeks. The drug may be so effective that the role of nutritional therapy may have to be redefined, and a shift away from using nutritional therapy to achieve more weight loss to rather using nutritional therapy to achieve more health gain may be required. Figure 1. Results are presented visually by treatment cohort and T2DM status at 12 months in this study, but data points and sample sizes are not stated, preventing interpretation and comparison of outcomes with those from the current study .A subgroup analysis of women on high dose of semaglutide (ie, semaglutide 1.7–2.4 mg weekly) was performed for all primary and secondary endpoints.STEP 4 examined the effect of continuing versus withdrawing semaglutide treatment after 20 weeks of initial therapy in adults with a BMI ≥30 kg/m2 (or ≥27 kg/m2 with ≥1 weight-related comorbidity) and without diabetes.(37) A total of 902 participants received semaglutide once-weekly during the run-in.Individual participant data will be shared in datasets in a de-identified and anonymized format.Contributed to interpretation of data; drafting of the manuscript; and critical revision of the manuscript for important intellectual content.Five studies (Wilding et al., 2021; Wadden et al., 2021; Rubino et al., 2021; Rubino et al., 2022; O'Neil et al., 2018), including 4,420 individuals, recorded changes of blood pressure related indicators, SBP and DBP.The first month of semaglutide treatment represents an adjustment period during which patients acclimate to the medication's effects while establishing sustainable lifestyle habits.“It was really exciting, because all of a sudden we were in a league where we knew that it would actually be much more impactful in terms of the effects on health,” Wilding says.Future studies are required to investigate the durability of weight loss and metabolic benefits over different lengths of therapy and in different subgroups. In the pre-marketing PIONEER-6 trial, a similar reduction in MACE rates was observed for oral semaglutide versus placebo, though statistical significance was not reached due to smaller event numbers than in SUSTAIN-6 . Oral semaglutide stands out as the pioneering orally administered peptide hormone-based treatment for type 2 diabetes (T2D). Updated values of HbA1c and body weight were analyzed using the mixed model for repeated measures. This study also focused on individuals with a 0.25mg to 2mg weekly dose of semaglutide. The near equivalent number of male and female patients in our study may have contributed to lower overall weight reduction. In addition, adherence was much more strongly confirmed in previous studies (6, 33–35), while our study relied only on EHR records of prescription as measure of semaglutide use. The attenuated weight loss performance of semaglutide alone may speak to the importance of implementing these lifestyle interventions concurrently with semaglutide prescription. As more robust weight loss is possible with newer medications, achieving and maintaining these cutoff point targets may become important benchmarks for tracking responses. Although our trial focused on CV events, many chronic diseases would benefit from effective weight management28. For lower BMI classes, discontinuation rates are higher in the semaglutide group but not the placebo group. This study was exempt from research ethics board approval as it relied on information in a public forum, meaning that the subjects of this research would have had no reasonable expectation of privacy. The shared experiences of semaglutide 2.4 mg users on the subreddit r/WegovyWeightLoss were explored. By gathering firsthand narratives, we sought to gain a deeper understanding of a patient perspectives and society's view on semaglutide 2.4 mg. Conversations on Reddit regarding GLP‐1RAs and their impact on mental health, substance use, and addiction have already begun to be explored using qualitative research on this platform 21, 22, 23. In STEP trials 1–3, the percent of participants in the semaglutide 2.4 mg vs placebo groups who experienced nausea was 33.7–58.2% versus 9.2–22.1%; diarrhea was 21.3–36.1% vs 11.9–22.1%; vomiting was 21.8–27.3% vs 2.7–10.8%; and constipation was 17.4–36.9% vs 5.5–24.5%. A once-daily oral version of the medication, at a maximum dose of 14 mg, was approved for treating type 2 diabetes in the US in 2019 and in Europe in 2020.(13) The dose of semaglutide for weight management is 2.4 mg injected subcutaneously once weekly (on the same day each week, with or without meals). Once-weekly subcutaneous semaglutide 1.0 mg was approved by the US Food and Drug Administration in 2017 and the European Medicines Agency in 2018 for the treatment of type 2 diabetes. The rate of any adverse event was greater in the continued semaglutide arm than the switched placebo arm (81.3% vs. 75.0%). Only patients who were able to tolerate semaglutide 2.4 mg were included in the randomization period, thus excluding those who could not achieve the top dose of the medication. In contrast with the placebo arm, the most common side effects in ≥10% of the semaglutide arm included nausea (58.2% vs. 22.1%), constipation (36.9% vs. 24.5%), diarrhoea (36.1% vs. 22.1%), vomiting (27.3% vs. 10.8%), and nasopharyngitis (22.1% vs. 24.0%). Given that the model was utilized for feature analysis, its low sensitivity was deemed acceptable and with high AUROC, specificity, and accuracy the analysis proceeded. Females experienced a greater proportion of the population losing higher percent of weight than males. Further information on the most common Phecode group coverage in the cohort observed over 52 weeks is shown in Table S1. In light of the bidirectional link between psychiatric disease and obesity, the weight outcomes of semaglutide in this context need to be studied . The efficacy of semaglutide in patients with active psychiatric diseases is not known since all individuals with major depressive disorders or other severe psychiatric disorders within the last two years were excluded from STEP trials . The observation in these individuals was the co-occurrence of semaglutide administration and mental health deterioration, while most of those were not on psychotropic medications related to significant weight gain. In our cohort, there was a trend toward higher rates of non-responders, defined as not achieving the weight loss benchmarks of either 3% after three months or 5% after six months, among males compared to females. That’s why maintaining healthy routines around food, movement, and stress is key for long-term success. These may include appetite return and weight to gradually creep back. After stopping semaglutide, it’s common for withdrawal symptoms to show up. All in all, with the right medical support, many people use semaglutide safely for years. Semaglutide is considered safe for long-term use—especially when a doctor is monitoring the treatment. 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. In a phase 2 trial, daily doses ofsemaglutide (0.05 mg, 0.1 mg, 0.2 mg, 0.3 mg, or 0.4 mg) were compared toliraglutide 3.0 mg daily or placebo. 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. Semaglutide for weight loss should be initiated at 0.25 mg once weekly and injectedsubcutaneously without regard to meals. All English-language articlesevaluating the efficacy and safety of semaglutide 2.4 mg for weight loss in humanswere included. The average decrease in body weight at week 68 was 13.2% in the semaglutide 2.4 mg group and 9.6% in the semaglutide 1.7 mg group versus 2.1% in the placebo group. At week 104, significantly more semaglutide- than placebo-treated participants lost ≥5% of baseline weight (77.1 vs 34.4%), as well as ≥10% (61.8 vs 13.3%), ≥15% (52.1 vs 7.0%), and ≥20% of baseline weight (36.1 vs 2.3%). Participants who received IBT combined with semaglutide 2.4 mg lost 16.0% of body weight at week 68 and achieved significantly greater improvements in multiple measures of cardiometabolic risk than the placebo-treated group. At week 68, semaglutide-treated participants lost an average of 14.9% of baseline weight, compared with 2.4% for those assigned to placebo. Orlistat, phentermine/topiramate ER, naltrexone ER/bupropion ER, and liraglutide produce placebo-subtracted weight losses of 2.6 kg (orlistat) to 8.8 kg (phentermine-topiramate) at 1 year.20 Semaglutide 1.0 mg, once-weekly, subcutaneous injection, was first approved as a treatment for type 2 diabetes in 2017. Change from baseline to follow-up in a–c weight, BMI, and HbA1c (all semaglutide OW cohort and subgroups), and d–f weight, BMI, and HbA1c (IPTW-adjusted semaglutide OW and comparator SGLT2i cohorts). Numerically, the greatest decreases in weight (5.2 kg) and BMI (1.9 kg/m2) were observed in the cohort of patients persistent to treatment and receiving ≥ 1 mg. Changes in weight, BMI, and HbA1c from baseline to follow-up with semaglutide OW are summarized in Fig. For the pairwise comparison of semaglutide OW versus SGLT2i cohorts, IPTW was used to adjust for imbalances in selected baseline patient characteristics between the treatment cohorts. At baseline, mean weight (mW) was 101.8 ± 24.6 kg and 95.2 ± 15.0 kg; mean body mass index (mBMI) was 36.7 ± 8.7 kg/m2 and 34.3 ± 5.3 kg/m2. In agreement with national regulation on retrospective studies on anonymized patients’ data, the need for informed consent was waived. Now, the observation that oral semaglutide was being initiated in patients with a relatively low prevalence of complications and use of insulin is reassuring that the oral delivery route is helping re-positioning GLP-1RA earlier in the natural course of T2D.The study has several limitations. Given Semaglutide’s wide therapeutic window, this relationship’s clinical significance is worth investigating. The persistent side effects detected in patients taking Semaglutide include gastrointestinal antagonistic episodes, such as nausea, vomiting, diarrhea, constipation, and abdominal cramps.53,54 Subcutaneous Semaglutide injection contains human GLP-1 receptor agonist semaglutide. GLP-1 is known to be a physiological hormone with several functions on glucose, acted and regulated by GLP-1 receptors.43 The concept of extension consequential in the long half-life of semaglutide is the binding of albumin that eventually leads to lowering renal clearance and defense from metabolic deprivation. Several combination medications are also in development, such as amylin/semaglutide and glucose-dependent insulinotropic polypeptide (GIP, formerly known as gastric inhibitory polypeptide)/GLP-1. Apart from gradual dose titration, data on how to prevent or treat gastrointestinal side effects are needed. Flexible titration may be necessary for patients who are experiencing side effects, and adjunctive therapies (e.g., antiemetic medications) may be helpful. This method is comparable to the management of hypertension, type 2 diabetes, hypercholesterolemia, sleep apnea, and related diseases. Such regain is common following the termination of AOM (and behavioral interventions) and underscores the need to prescribe these medications on a long-term basis with the recognition that obesity, for most individuals, is a chronic condition that can be managed by not cured. The initial qualitative study included concept elicitation interviews with 30 patients to generate the instrument content and cognitive interviews with 20 patients to assess relevance, clarity, and comprehensiveness of the questionnaire .We excluded r/Tirzepatide and r/Mounjaro as they focus on GLP‐1/GIP medications, which are different from the GLP‐1 receptor agonists used in this study.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.Newer pharmacological interventions include tirzepatide (glucose-dependent insulinotropic polypeptide and GLP-1 agonist), which has demonstrated efficacy in people with T2DM in the SURPASS-2 trial,10 as well as sodium glucose cotransporter 2 (SGLT-2) inhibitors (eg, dapagliflozin, canagliflozin) that are used to manage T2DM but can also induce clinically significant weight loss.11This qualitative study aims to explore the narratives of individuals using semaglutide 2.4 mg for weight management, as expressed in Reddit posts.IS and OS therapy were well tolerated, and no patients in both groups experienced severe adverse events like nausea or vomiting. Annual inflation estimates are calculated as an average of the first three months of the year. These thresholds are based on the 25th and 75th percentile of workers’ earnings as reported by the Bureau of Labor Statistics using data from the Occupational Employment Statistics (OES) (2023).5 The cutoffs were inflation-adjusted and rounded to the nearest thousand. The survey asks firms what percentage of their employees earn more or less than a specified amount in order to identify the portion of the workforce that has relatively lower or higher wages. In contrast, large firms—especially those with 1,000 or more workers—have the greatest influence on statistics related to covered workers. Beginning in 2025, firms with fewer than 10 employees were excluded from the survey universe. Stephen L Atkin, MD Although concrete evidence regarding its effect on cardiovascular outcomes is pending, it is worth noting that the same active compound, when given subcutaneously in the SUSTAIN-6 trial, reduced the occurrence of major adverse cardiovascular events (MACE) compared to a placebo . These attributes position oral semaglutide as a favorable choice for early T2D treatment when metformin monotherapy fails or is contraindicated . During the 18-month observation period, oral semaglutide demonstrated significant reductions in HbA1c, with a maximum change of − 0.9%, and 42.1% of patients achieved HbA1c values below 7.0%. In the majority of patients (68.3%) oral semaglutide was used as a second-line drug, mostly with metformin. Comparison of the performance of common measures of weight regain after bariatric surgery for association with clinical outcomes. Semaglutide may herald a new era in the management of obesity, introducing widespread use of pharmacotherapy to meet a large unmet clinical need. Additionally, postmarketing reports of ileus in patients on semaglutide have led the FDA to add a warning about gastrointestinal ileus on the semaglutide label, but a causal association has not been proven. However, prospective studies are warranted to confirm the neuropsychiatric safety of semaglutide. In addition, categorical and binary BMI measures based on BMI value were reported for the baseline and follow-up periods. In the comparator SGLT2i cohort, those with any prior SGLT2i use during the baseline period or any baseline or follow-up use of any GLP-1 RA were excluded. Patients with a pharmacy claim for any SGLT2i during the baseline or follow-up periods were excluded for the comparison with SGLT2is. From week 20 to week 68, systolic blood pressure remained stable with continued semaglutide and significantly increased with placebo (difference, −3.9 mm Hg 95% CI, −5.8 to −2.0 mm Hg; P Figure 2B; eFigure 3 in Supplement 1), with no change in diastolic blood pressure in either treatment group (Table 2; eTable 5 and eFigure 5 in Supplement 1). Data presented in panels A, B, and C are observed data for the full analysis set from the in-trial period (the time from week 0 to the date of last contact with trial site). For interpretation, these data are expressed as relative percent change and estimated relative percent difference between groups, respectively, and were calculated using the formula (estimated ratio − 1) × 100.fData are observed proportions of participants who gained weight from week 20 to week 68, and estimated odds ratio (95% CI). The differences between mean percent changes in body weight, fasting serum insulin, and fasting lipid profile and mean changes in hemoglobin A1c are expressed in percentage points.cThe Short Form 36 Version 2 Health Survey, Acute Version (SF-36) measures health-related quality of life and general health status. Both glucagon-like peptide 1 receptor agonists (GLP-1 RAs) and sodium-glucose co-transporter 2 inhibitors (SGLT2is) are now recommended by the ADA for the treatment of T2D, according to the individual needs of the patient . T2D is a chronic, progressive disease with substantial clinical and economic impact 2, 3. More than 38 million people in the United States (USA) have diabetes, of which 90–95% have type 2 diabetes (T2D) . For this reason, we will continue to report our results for these questions weighted by the number of covered workers in responding firms.Starting in 2017, respondents were allowed to volunteer that their plans did not cover outpatient surgery or hospital admissions. Therefore, for these topics, aggregate variables represent the attributes of the firm’s largest plan type, and are not a weighted average of all of the firms plan types. Our analysis does not show significant differences in responses to key variables among these incentive groups.In 2017, weights were not adjusted using the nonresponse adjustment process described in previous years’ methods. Therefore, starting in 2016, we altered the health insurance premium question pathway for firms with between employees to match that of firms with 3-19 employees rather than firms with 50 or more employees. Firm-weighted estimates resulting from this change show only small changes from previous estimates, because smaller firms have much more influence on national estimates. These novel medications will provide patients and providers with additional choices for effective weight management strategies. While semaglutide has a reduced dosing frequency relative to all other obesity medications, it is a subcutaneous injection. Patient preference is an important consideration in providing high-quality obesity treatment. Anti-obesity medications are only used by 3% of eligible US adults.87 A substantial barrier to the use of semaglutide, like other anti-obesity medications, is insurance coverage; 68% of payments for anti-obesity medications are out-of-pocket. In exploratory analyses, semaglutide has demonstrated renoprotective effects.85 These effects are most evident in patients with preexisting chronic kidney disease.85 Semaglutide is not excreted by the kidneys, so dose reduction with impaired kidney function is not necessary. Five studies (Wilding et al., 2021; Wadden et al., 2021; Rubino et al., 2021; Rubino et al., 2022; O'Neil et al., 2018), including 4,415 individuals, reported changes in TC, HDL, LDL, VLDL, and TG. 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. Meta-analysis results are shown in Figure 8, Supplementary Figure S7, and Supplementary Table S3. Five studies (Wilding et al., 2021; Wadden et al., 2021; Rubino et al., 2021; Rubino et al., 2022; O'Neil et al., 2018), including 4,420 individuals, recorded changes of blood pressure related indicators, SBP and DBP. STEP 4 investigated the impact of continued semaglutide 2.4 mg treatment, vs switching to placebo, on maintenance of weight loss in participants who reached 2.4 mg of semaglutide during a run-in period. Subcutaneous (s.c.) semaglutide, a glucagon-like peptide-1 analogue, has shown clinically-relevant weight loss in a phase 2 trial in people with obesity. For 68 weeks, patients treatedwith semaglutide lost an average of 15.8% body weight compared to 6.4% withliraglutide (p21 STEP 1 evaluated the change in body weight and weight reduction of at least 5%between semaglutide 2.4 mg and placebo in adults who were obese or overweight withat least one weight-related comorbidity and did not have diabetes. By giving semaglutide, a GLP-1 receptor agonist, one is effectively giving back a satiety hormone that was decreased by the body to fight weight loss. The weight loss seen here — 18% if you factor in the lead-in period for a study that retained 98% of participants — is phenomenal. “This is very promising, both in terms of the degree of weight loss, the ability to counter weight regain and to have a bridge the gap between current medical treatment and bariatric surgery for obesity,” Rubino said. Primary endpoint was percent change in body weight from week 20 to week 68; confirmatory secondary endpoints were changes in waist circumference, systolic blood pressure and physical functioning. One of the main goals of semaglutide therapy is a reduction in HbA1c levels to improve glycemic control. Pooled data from three randomized controlled trails and a nationwide registry-based cohort have consistent findings. Semaglutide treatment is also found to decrease myocardial diastolic stiffness and improve actin-myosin and muscle contraction pathways . Its benefits extend beyond glycemic control, including weight reduction and anti-inflammatory effects, which collectively lower cardiovascular risks. Semaglutide, a GLP-1 receptor agonist, has demonstrated superior cardioprotection for people with T2DM compared to other treatments. GLP-1 receptor agonists approved in the United States for treating type 2 diabetes include exenatide, liraglutide, lixisenatide, albiglutide, and dulaglutide.32 According to reviews, semaglutide is at least as potent and possibly even more so than other GLP-1s.38 Weight management is crucial for a healthy lifestyle and for reducing obesity-related complications. The findings from the review suggest that semaglutide appears to be beneficial, most notably in its contribution to weight reduction. Semaglutide promotes weight loss via appetite and hunger suppression, decreases energy intake, controls eating, and depresses the relative fondness for fatty, energy-dense foods. The compound closely resembles natural GLP-1, so your body doesn’t eliminate it rapidly like other peptides. Visceral fat comprises just 6-20% of total body fat but carries disproportionate metabolic consequences. Meanwhile, subcutaneous fat contributes to body size but predicts far less disease risk. Even people with normal body mass index can carry excess visceral fat and face elevated disease risk. Insulin resistance, unhealthy cholesterol profiles, increased glucose production, and fat buildup within the liver itself. 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 . Fasting insulin values were available in 28 participants, with insulin resistance, defined as high homeostatic model assessment for insulin resistance (HOMA-IR) ≥ 1.9 , being reported in 24 out of 28 cases (86%), while severe insulin resistance, defined as HOMA-IR exceeding 4, being recorded in 15 out of 28 participants (53.5%). 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. In addition to the published STEP trials, the programme includes three further ongoing global phase IIIa studies in adolescents with obesity (STEP TEENS),69 in individuals with heart failure and obesity (STEP‐HFpEF)70 and in individuals with heart failure and obesity with type 2 diabetes (STEP‐HFpEF‐DM)71 (Figure 2). The STEP trials excluded participants with renal impairment (estimated glomerular filtration rate 2; except STEP 2, 2 or 2 with SGLT2i).38, 39, 40, 41, 42, 43, 44 However, the prescribing information states that no dose adjustment of semaglutide is recommended for patients with renal impairment.20 The encouraging data from validated patient‐reported outcomes (Short Form‐36 Version 2 Health Survey, Acute Version in STEP 1‐4 and Impact of Weight on Quality of Life‐Lite Clinical Trials Version questionnaire in STEP 1 and 2) point towards the benefits of semaglutide 2.4 mg being directly perceived by study participants. 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. Learn what patients experience, what evidence exists, and key limitations. Take the first step today—explore Ivy Rx’s Semaglutide options and start your transformation! Co-primary, confirmatory secondary, and selected supportive secondary and exploratory trial endpointsa AInformation on the sex of participants was collected by investigators by selecting from ‘male’ or ‘female’ on a case report form. Further analyses are needed to compare the costs and benefits of semaglutide relative to those for behavioral and surgical approaches. In 68.3% of patients, oral semaglutide was being used as a second-line diabetes drug. The primary study endpoint was the change in HbA1c from baseline through follow-up visits with confirmed prescription for oral semaglutide. The change over time in HbA1c and body weight were estimated using the mixed model for repeated measures. The dose of oral semaglutide at each visit was recorded along with the information on whether the prescription was confirmed or not.The primary study endpoint was the change in HbA1c from baseline through follow-up visits with confirmed prescription for oral semaglutide. The ongoing SOUL trial is further evaluating the rates of cardiovascular events in individuals with T2D receiving oral semaglutide or placebo . Human data is limited, and that means we can’t claim these medications are safe in pregnancy. If you’re offered a registry, joining is optional, but it can help improve care for future patients. This matches FDA labeling for these medications, and it reflects the fact that we don’t have enough safety data in pregnancy to recommend continuing them. In most cases, your healthcare team will advise you to stop the medication as soon as pregnancy is confirmed. If you get pregnant while taking medication, you should contact your healthcare team right away, and you will likely be advised to stop the medication immediately. This article will review its role, mechanism of action, pharmacokinetics, pharmacodynamics, adverse drug reactions, and drug-drug interactions, focusing on obesity mechanisms.Semaglutide has therapeutic applications for T2DM, obesity, and other metabolic and neurodegenerative disorders.In addition, our study consisted of mostly White, college-educated women with no financial strain, potentially limiting the generalizability of the findings.Semaglutide improves glycemic control and reduces cardiovascular risk factors in patients with T2DM 8,10.All participants provided written informed consent prior to trial‐related activities.Collected data as an investigator in some of the underlying trials, interpreted the data and wrote the manuscript.Non-grandfathered health plans are required to cover some services, such as preventive care, without cost-sharing.The present study also uses longer term data than that of previous studies and excludes IBT to enable more focused comparison between pharmacological therapies. 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. In addition, two studies did not mention allocation concealment (Hjerpsted et al., 2018; Jensterle et al., 2021). The proportions of individuals with different types of comorbidities at baseline were presented, especially the metabolic syndrome, such as dyslipidemia, hypertension, obstructive sleep apnea, and cardiovascular disease. The other four studies contained adults with a BMI of 30 or greater without comorbidities totally (O'Neil et al., 2018; Friedrichsen et al., 2021; Hjerpsted et al., 2018; Jensterle et al., 2021). Tan et al. found that subcutaneous semaglutide led to an 11.85% reduction in weight , while Gao et al. reported a significant reduction in body weight, body mass index (BMI), and waist circumference . A series of systematic reviews and meta-analyses have consistently demonstrated the efficacy of semaglutide in promoting weight loss in individuals without diabetes. This systematic review will evaluate the effects of semaglutide on individuals with obesity or overweight without diabetes. This systematic review evaluates the efficacy and safety of semaglutide in individuals with obesity or overweight without diabetes. Most of the studies included demonstrated a positive effect of semaglutide for obesity treatment. ETD, estimated treatment difference; sema, semaglutide. There was no detectable difference in hepatobiliary or gastrointestinal SAEs comparing semaglutide with placebo in any of the four BMI classes we evaluated. Rates (events per 100 years of observation) of SAEs were 43.23, 43.54, 51.07 and 47.06 for semaglutide and 50.48, 49.66, 52.73 and 60.85 for placebo, with no evidence of heterogeneity. The review also discusses the cardiovascular benefits suggested by the trials, although the completion of the SOUL trial is waiting for definitive conclusions. Meier discusses the efficacy of semaglutide, the only GLP-1 RA available in both injectable and oral formulations. Semaglutide is approved for chronic weight management in adults and is the first drug approved for this purpose since 2014. Moreover, the sensitivity analysis was assessed to evaluate the stability and reliability of the results. The meta-analysis results were shown by forest plots, and the publication biases were observed by funnel plots (Biljana et al., 1999). The fixed effect model was used when there was no statistical heterogeneity in the included studies (Ⅰ2 ˂ 50% and p ˃ 0.10); otherwise, the random effect model was represented (Ⅰ2 ≥ 50% or p ˂ 0.10) (Chen and Benedetti, 2017). How to Maintain Weight Loss with Semaglutide This analysis of the STEP 1 trial evaluated the impact of subcutaneous (s.c.) semaglutide, a glucagon-like peptide-1 analogue, on body composition in adults with overweight/obesity using dual energy X-ray absorptiometry (DEXA). Once-weekly semaglutide was superior to placebo in terms of the percentage change and absolute change in body weight. Additionally, this study provided information on patient demographic and baseline clinical data, dosing, and weight outcomes and offered a comprehensive view of the real-world effectiveness of semaglutide 2.4 mg and tirzepatide. The strengths of this study include its large sample size of 9916 patients, which increases the generalizability of the observed weight loss results to the broader US population compared with the smaller patient populations enrolled in randomized clinical trials. Bayesian framework and Markov Chain Monte Carlo (MCMC) simulation were used for modelling, with the inclusion of vague prior distributions in line with guidance on evidence synthesis from the NICE Decision Support Unit.20–22 All NMA models were fitted using WinBUGS software (MRC Biostatistics Unit, Cambridge, UK); normal likelihood, identity link (CFB weight) and binomial, logit link (proportion of participants losing ≥5% baseline fasting body weight). Additional searches of conference proceedings (from the last 3 years), health technology assessment (HTA) body websites, clinical trial registries (ClinicalTrials.gov and World Health Organization International Clinical Trials Registry Platform), and reference lists of included studies were performed to identify other relevant evidence. The objective of this systematic literature review (SLR) and meta-analysis was to compare RCT evidence for weekly semaglutide 2.4 mg with that of relevant pharmacological comparators for weight management in people who have overweight or obesity. Until the results of STEP 8 (weekly semaglutide 2.4 mg versus daily liraglutide 3.0 mg) were published in 2022,16 all randomized controlled trials (RCTs) in the STEP program have compared semaglutide with placebo; therefore, to compare semaglutide with other active comparators, indirect treatment comparison is required. Extracted data included study design, location, population characteristics, sample size, treatment arms, treatment duration, primary endpoints, and baseline demographic characteristics (e.g., age, sex, body weight, BMI, waist circumference, and blood pressure).Keep reading to learn more on how this treatment can support various aspects of health and vitality.Following this, 535 participants – who already achieved their target maintenance dose of 2.4 mg weekly – were randomised to continue on their 2.4-mg-per-week dose of semaglutide for an additional 48 weeks.Since 2017, we have attempted to increase the number of completes by expanding the number of non-panel firms in the sample.Fully 32.0% of semaglutide-treated participants lost 20% or more of baseline weight, compared with only 1.7% of the placebo group.In this regard, it is successfully recognized that semaglutide may be particularly suitable for obese patients with cardiovascular disease.The calculation of the weights followed a similar approach to previous years, but with several notable changes in 2003.In addition to offering wellness programs, many large firms offer health screening programs. Liraglutide was also effective, albeit less than semaglutide, in causing ≥5%, ≥10%, ≥15%, and ≥20% weight loss at 68 weeks in 58.1%, 25.6%, 12%, and 6% of participants, respectively. Moreover, the proportions of participants who had ≥5%, ≥10%, and ≥15% weight loss at week 68 with semaglutide 2.4 mg were 83%, 61%, and 41%, respectively. The main exclusion criteria were previous or planned anti-obesity treatment or surgery and bodyweight changes of 5 kg or more in the past 3 months before screening.