Estimated means are provided with s.e.m., and estimated treatment differences are provided with 95% CI. The proportions of individuals with BMI −2 who achieved sex- and race-specific cutoff points for WC (indicating increased metabolic risk) were evaluated at week 104. The scale was calibrated yearly as a minimum unless the manufacturer certified that calibration of the weight scales was valid for the lifetime of the scale. There were 408 prescriptions of subcutaneous injections of semaglutide between January 1, 2021, and March 15, 2022, at the Mayo Clinic Health System.So how was it discovered that it could also help people lose weight?Individual weight changes at 104 weeks for the in-trial populations for semaglutide and placebo are depicted in Fig.And I think the - you know, these companies would say, you know, this is a highly effective new option that we're offering to our members, our patients.The Mayo Clinic institutional review board approved the study and waived the need for informed consent owing to its minimal-risk nature.In the SELECT trial, patients did not enroll for the specific purpose of weight loss and received standard of care covering management of CV risk factors, including medical treatment and healthy lifestyle counseling, but without a specific focus on weight loss.You eat less, and you lose weight.So how did it go from, oh, it's helping diabetics lose weight as a side effect, to being the most sought-after weight-loss drug in the world?Each patient’s percentage change in body weight is plotted as a single bar.Full size imageWC change from baseline to 104 weeks has been reported previously in the primary outcome paper21. And the study looked at adults who had previously had heart issues like strokes and put them on Wegovy and wanted to see, does this reduce your risk of having another heart incident like a stroke? And we had this big, important trial come out last year from Novo Nordisk, the company that makes Ozempic and Wegovy in August. And so what the big push has been by the pharma industry is to try to prove these are drugs that are going to reduce costs for insurers in other respects. Do we see these drugs actually improving health outcomes? These data, representing the longest clinical trial of the effects of semaglutide versus placebo on weight, establish the safety and durability of semaglutide effects on weight loss and maintenance in a geographically and racially diverse population of adult men and women with overweight and obesity but not diabetes. ETD, estimated treatment difference; sema, semaglutide.Full size imageAmong in-trial (intention-to-treat principle) patients at week 104, weight loss of ≥5%, ≥10%, ≥15%, ≥20% and ≥25% was achieved by 67.8%, 44.2%, 22.9%, 11.0% and 4.9%, respectively, of those treated with semaglutide compared with 21.3%, 6.9%, 1.7%, 0.6% and 0.1% of those receiving placebo (Fig. 2a). This prespecified analysis of the SELECT trial investigated weight loss and changes in anthropometric indices in patients with established CVD and overweight or obesity without diabetes, who met inclusion and exclusion criteria, within a range of baseline categories for glycemia, renal function and body anthropometric measures. This possibility might be one explanation for our relatively lower rate of medication discontinuation compared with the 7% reported in the STEP 1 trial.18 As described in previous studies, no unexpected safety issues were recorded for our cohort of patients.34 Similar to our reported results, gastrointestinal symptoms, particularly nausea, are the most commonly reported adverse effects with semaglutide.18 We also report a significant number of patients with fatigue, which was not reported in previous studies.18 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. Of the 28 patients with type 2 diabetes, 11 (39.3%) were using a combination of insulin with metformin, empagliflozin, and/or glipizide. The effect of semaglutide (versus placebo) on mean percentage body weight loss as well as reduction in WC was found to be heterogeneous across several population subgroups. Bars depict the proportion (%) of patients receiving semaglutide or placebo who achieved ≥5%, ≥10%, ≥15%, ≥20% and ≥25% weight loss. Individual weight changes at 104 weeks for the in-trial populations for semaglutide and placebo are depicted in Fig. The SELECT trial (Semaglutide Effects on Heart Disease and Stroke in Patients with Overweight or Obesity) studied patients with established CVD and overweight or obesity but without diabetes. There were variations in the weight-loss response. Likewise, there were similar improvements in the semaglutide group for anthropometrics (WC and WHtR). The dots show estimated treatment differences, and the error bars show 95% CIs. 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. At week 208, average reduction in WC was −7.7 cm with semaglutide versus −1.3 cm with placebo, with a treatment difference of −6.4 cm (95% CI −7.18 to −5.61; P 21. These waterfall plots show the variation in weight-loss response that occurs with semaglutide and placebo and show that weight loss is more prominent with semaglutide than placebo. Two-year effects of semaglutide in adults with overweight or obesity: the STEP 5 trial And these drugs just first started coming to market in the early 2000s.They say that these drugs are completely changing everything that they've struggled with in their lives.Producing and sustaining durable and clinically significant weight loss with lifestyle intervention alone has been challenging11.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 trajectory of WC change mirrored that of the change in body weight.They started studying this higher dose version for weight loss specifically.Patients with a history of bariatric procedures, taking other antiobesity medications, and with an active malignant neoplasm were excluded. But in weight loss specifically, it has a variety of effects in the body, including sort of acting through the brain, activating the brain to promote feelings of satiety and lessening appetite. So I definitely want to talk about how these drugs are changing a lot of things, like the diet industry and our cultural views about bodies and weight loss. You know, Elon Musk has said he's used one of these drugs for weight loss. So you see that drug really taking off on places like TikTok and people showing off how much weight loss they've been able to achieve. A total of 175 patients (132 women 75.4%; 154 White patients 88.0%; mean SD age, 49.3 12.5 years; mean SD BMI, 41.3 9.1) of 408 patients with semaglutide prescriptions were included in the final cohort for analysis (Figure 1 and Table 1). The baseline demographic and anthropometric data were normally distributed and are summarized as mean (SD) values. In addition, we collected information on any adverse effects experienced after the initiation of semaglutide treatment. You know, WeightWatchers didn't really offer weight-loss drugs before, you know? How have these drugs impacted the weight-loss industry? But, you know, some people just take these drugs and they feel so ill that they just can't stay on them, right? And so they say, we have this long track record of using them in people with diabetes. And one thing that proponents of these drugs, you know, really emphasize is that they've been used - GLP-1 specifically have been used in diabetes for, you know, almost 20 years. Estimated means are provided with s.e.m., and estimated treatment differences are provided with 95% CI.Patients without type 2 diabetes achieved higher weight loss outcomes than those with type 2 diabetes, which is also shown in our study.19Data will be shared with bona fide researchers who submit a research proposal approved by the independent review board.And it was a big, important study.In our cohort, patients lost approximately 6.7 kg at 3 months and 12.3 kg at 6 months, equivalent to 5.9% of weight lost at 3 months and 10.9% of weight lost at 6 months.Among in-trial (intention-to-treat principle) patients at week 104, weight loss of ≥5%, ≥10%, ≥15%, ≥20% and ≥25% was achieved by 67.8%, 44.2%, 22.9%, 11.0% and 4.9%, respectively, of those treated with semaglutide compared with 21.3%, 6.9%, 1.7%, 0.6% and 0.1% of those receiving placebo (Fig. 2a).In our cohort of 175 patients, 94 (53.7%) had weight loss of at least 5% and 26 (14.9%) had weight loss of 10% or more at 3 months.The findings of this cohort study suggest that semaglutide is clinically effective for weight loss at 3 and 6 months for people with overweight or obesity. Although our study lacked the stringent and closely controlled nature of RCTs, we report similar weight loss results within the same time period as in RCTs. In our cohort, patients lost approximately 6.7 kg at 3 months and 12.3 kg at 6 months, equivalent to 5.9% of weight lost at 3 months and 10.9% of weight lost at 6 months. 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). In our cohort of 175 patients, 89 patients (50.9%) had class 3 obesity (BMI, ≥40). In the SELECT cardiovascular outcomes trial, semaglutide showed a 20% reduction in major adverse cardiovascular events in 17,604 adults with preexisting cardiovascular disease, overweight or obesity, without diabetes. This paper reviews data on the mechanism of action, weight-loss and cardiometabolic efficacy, and safety of semaglutide 2.4 mg/week for obesity. Another serious limitation is the exclusion of patients who did not reach 3 months of follow-up, which might have resulted in an overestimation of the association of semaglutide with body weight. Considering the observational nature of this study, we could not compare weight loss outcomes between patients receiving semaglutide and controls. 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. 6 depict a graded increase in the proportion discontinuing semaglutide, but not placebo. For this analysis, with death modeled as a competing risk, we tracked the proportion of in-trial patients for whom drug was withdrawn or interrupted for the first time (Fig. 6, left) or cumulative discontinuations (Fig. 6, right). The lowest tertile of the SELECT population at baseline had a mean WHtR 27, suggesting that the trial population had high WCs. The trajectory of WC change mirrored that of the change in body weight. And we had this big, important trial come out last year from Novo Nordisk, the company that makes Ozempic and Wegovy in August.We performed a retrospective review of the electronic medical records (EMRs) of patients in the Mayo Clinic Health System using semaglutide between January 1, 2021, and March 15, 2022.In one study including 1306 patients taking semaglutide, 2.4 mg, weight loss of approximately 6% was achieved by week 12 and 12% was achieved by week 28.18 Our results reflect similar weight loss outcomes within the same period, particularly for patients taking doses of 1.7 mg and 2.4 mg.There was no detectable difference in hepatobiliary or gastrointestinal SAEs comparing semaglutide with placebo in any of the four BMI classes we evaluated.Mean values of fasting glucose, hemoglobin A1c, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides at baseline are presented in Table 1.Clinically meaningful weight loss was evident in the semaglutide group within a broad range of baseline categories for glycemia and body anthropometrics. For secondary end points, categorical data were analyzed using the Fisher exact test, and the 2-sample independent t test was used for continuous data. During data abstraction, we confirmed the medication start date from physicians’ EMR notes or physician-patient communications because there might be a delay between the day of prescription and the start of medication (eg, insurance approval delay and drug availability). We also collected information on visits with dietitians and behavioral bariatric psychologists after the first day of starting semaglutide until the last day of follow-up or until the medication was discontinued. There were 408 prescriptions of subcutaneous injections of semaglutide between January 1, 2021, and March 15, 2022, at the Mayo Clinic Health System. This study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline. It would be meaningful to have quantitation of fat mass, lean mass and muscle mass, especially given the wide range of body size in the SELECT population. Another limitation is the lack of information on body composition, beyond the anthropometric measures we used. We observed that Asian patients were less likely to be in the higher BMI categories of SELECT and that the population of those with BMI −2 had a higher percentage of Asian race. SELECT also did not include individuals who have excess abnormal body fat but a BMI −2. Although the data set is rich in numbers and diversity, it does not have the numbers of individuals in racial subgroups that may have revealed potential differential effects. We performed a post hoc analysis of patients with or without type 2 diabetes and of patients receiving different doses of semaglutide. Our secondary end points included the percentage of patients who achieved a categorical weight loss of 5% or more, 10% or more, 15% or more, and 20% or more. 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. There's also a lot of concern, are people going to be told to take these drugs merely based on their weight, right? Within each obesity class (−2, 30 to −2, 35 to −2, and ≥40 kg m−2), there were fewer SAEs in the group receiving semaglutide compared with placebo. Each patient’s percentage change in body weight is plotted as a single bar.Full size imageWC change from baseline to 104 weeks has been reported previously in the primary outcome paper21. These waterfall plots show the variation in weight-loss response that occurs with semaglutide and placebo and show that weight loss is more prominent with semaglutide than placebo.Fig. Numbers shown below each panel represent the number of patients contributing to the means. The baseline characteristics of the population have been reported24. In fact, the World Health Organization defines clinical obesity as ‘abnormal or excessive fat accumulation that may impair health’1. Medical Treatments But it could be an important factor in terms of getting insurers, at least for this specific group, so people with a high risk for further heart incidents. And it was a big, important study. It brought down the risk of heart - these kinds of heart issues by about 20% relative to a placebo. And these drugs just first started coming to market in the early 2000s. And Ozempic was originally created to treat Type 2 diabetes. And Viagra, just to remind people, was originally created to treat high blood pressure, but then people started using it to treat erectile dysfunction. An essential round-up of science news, opinion and analysis, delivered to your inbox every weekday. In other RCTs following up with patients treated with semaglutide, 2.4 mg, adverse effects were reported in 90% of patients over 68 weeks.18 Some possible explanations for the lower reported adverse effects in our study include patients not reaching the maximum dose of semaglutide (ie, 1.7 and 2.4 mg) and the shorter duration of follow-up (24 vs 68 weeks). In our study, patients with type 2 diabetes lost less weight compared with those without type 2 diabetes. In a multicenter clinical experience assessing the outcome of FDA-approved AOMs (eg, phentermine-topiramate, liraglutide, orlistat, and naltrexone-bupropion), weight loss of 5.0% was achieved at 3 months compared with 5.9% in the present study, and weight loss of 6.8% was achieved at 6 months compared with 10.9% in the present study. Patients without type 2 diabetes achieved higher weight loss outcomes than those with type 2 diabetes, which is also shown in our study.19 And the study looked at adults who had previously had heart issues like strokes and put them on Wegovy and wanted to see, does this reduce your risk of having another heart incident like a stroke?There is a plateau of weight that occurs after weight loss with all treatments for weight management.We included patients who had at least a 3-month follow-up documented in the EMR with a BMI of 27 or more who were prescribed weekly semaglutide subcutaneous injections of 0.25, 0.5, 1, 1.7, and 2.4 mg with the primary goal of weight loss.The average percentage weight-loss trajectories with semaglutide and placebo over 4 years of observation are shown in Fig.SELECT also did not include individuals who have excess abnormal body fat but a BMI −2.With roughly 2 out of 3 adults in America classified as overweight or obese, these drugs now have people talking about weight loss in new ways.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).The SELECT trial (Semaglutide Effects on Heart Disease and Stroke in Patients with Overweight or Obesity) studied patients with established CVD and overweight or obesity but without diabetes.In patients with type 2 diabetes and high CV risk, semaglutide at doses of 0.5 mg and 1.0 mg has been shown to significantly lower the risk of CV events20. We collected patient weights in kilograms that were obtained either using a calibrated scale during office visits or reported by the patients during virtual visits and clinical communications with the physician. We abstracted demographic, anthropometric, and laboratory data within 30 days before or after 3 and 6 months. Owing to high insurance denials and the national shortage of semaglutide, we subsequently excluded those patients from the analysis. We performed a retrospective review of the electronic medical records (EMRs) of patients in the Mayo Clinic Health System using semaglutide between January 1, 2021, and March 15, 2022. Multiple weight loss interventions have been developed during the past decades. And that's, you know, not what these drugs were developed for. Or, you know, even they, you know, obviously, there are definitely a lot of cases of, like, thin people who are using Ozempic to shed a few pounds. This person doesn't deserve to lose weight easily, right? Investigators were provided with guidelines for, and encouraged to follow, evidence-based recommendations for medical treatment and lifestyle counseling to optimize management of underlying CVD as part of the standard of care. Investigators were allowed to reduce the dose of study product if tolerability issues arose. The starting dose was 0.24 mg once weekly, with dose increases every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg per week) until the target dose of 2.4 mg was reached after 16 weeks. National and institutional regulatory and ethical authorities approved the protocol, and all patients provided written informed consent. Analysis of covariance with treatment and baseline values was used to estimate the treatment difference. Supplementary Table 1 outlines SELECT patients according to baseline BMI categories. The SELECT study enrolled 17,604 patients (72.3% male) from 41 countries between October 2018 and March 2021, with a mean (s.d.) age of 61.6 (8.9) years and BMI of 33.3 (5.0) kg m−2 (ref. 21). Furthermore, the data allow examination of changes in anthropometric measures such as BMI, waist circumference (WC) and waist-to-height ratio (WHtR) as surrogates for body fat amount and location22,23. We've heard more recently Oprah say she's been using it for weight loss maintenance. We've heard all kinds of prominent people talk about taking versions of these drugs at this point. And I think at some point during the time of the shortage of this new treatment, people kind of put two and two together. Glucagon-like peptide-1 medicines and cancer Data are represented as number and percentage of patients. The dots show estimated treatment differences and the error bars show 95% confidence intervals. Declares having received honoraria related to participation on this trial and has no financial conflicts related to this publication. All authors contributed to data interpretation, review, revisions and final approval of the manuscript. D.H.R. was responsible for data analysis and manuscript preparation. This person doesn't deserve to lose weight easily, right?And there are other studies like that in process looking at health outcomes being improved by weight loss on these drugs.For personalized thyroid treatment plans and expert guidance, reach out to Dr. Anshul Gupta.Our approach focuses on holistic and sustainable methods to manage thyroid health and enhance energy levels.This plateau has been termed the ‘set point’ or ‘settling point’, a body weight that is in harmony with the genetic and environmental determinants of body weight and adiposity31.But can you first tell us how these drugs work?Although the data set is rich in numbers and diversity, it does not have the numbers of individuals in racial subgroups that may have revealed potential differential effects.We want to make sure that these drugs actually do improve people's health and they don't just help people lose weight, right?Do we see these drugs actually improving health outcomes? ETD, estimated treatment difference; HbA1c, glycated hemoglobin; MI, myocardial infarction; PAD, peripheral artery disease; sema, semaglutide. At baseline, mean WHtR was 0.66 for the study population. WC change from baseline to 104 weeks has been reported previously in the primary outcome paper21. Each patient’s percentage change in body weight is plotted as a single bar. ETD, estimated treatment difference; sema, semaglutide. And I think the - you know, these companies would say, you know, this is a highly effective new option that we're offering to our members, our patients. And actually, my colleague Ellen Huet and I did a profile of WeightWatchers getting into the prescription drug business for a Businessweek cover last year. And we also saw another big rival, Noom, get into the prescription weight-loss business itself. And that's a reality, you know, quitting these drugs due to the side effects. Have there been any long-term studies on use of these drugs? Ozempic is not technically approved for weight loss.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).In the semaglutide group, 12.0% of patients achieved a BMI −2, which is considered the healthy BMI category, compared with 1.2% for placebo; per study inclusion criteria, no patients were in this category at baseline.And then eventually one of the things we started seeing was that the weight loss was improving with the new generations of diabetes drugs.As more robust weight loss is possible with newer medications, achieving and maintaining these cutoff point targets may become important benchmarks for tracking responses.An essential round-up of science news, opinion and analysis, delivered to your inbox every weekday.The lowest tertile of the SELECT population at baseline had a mean WHtR 27, suggesting that the trial population had high WCs. So in order to get weight-loss drugs approved, because there's such a long and terrible safety track record in this category, developers do have to run pretty long-term studies. Has a ban on the use of Ozempic for anything other than the treatment of Type 2 diabetes, and I think Belgium is also considering a temporary ban like this too. So we've seen in, you know, anecdotal reports and also in studies that the pharmaceutical companies have done that when they - when people stop taking these medications, they tend to regain weight. But generally, this class of drugs is going to run over $10,000 a year at list prices. It really has to do with how people perceive it and how things are categorized. We've, as I mentioned before, seen some research finding that people who've previously had things like strokes had their stroke risk cut by being on Wegovy. And - you know, and by the way, the advocate I mentioned who I spoke with said, you know, advocates are also concerned about, are these drugs as good as we're being told they are, right? So I think there's a lot of, you know, interest in what is - what are the effects of these drugs going to be culturally. And it's causing all kinds of difficult situations for people. And in the meantime, that is resulting in a situation where you have a lot of people competing for a limited amount of drug. And Novo Nordisk has said, we were pretty taken off guard by how quickly this drug got picked up by patients and doctors. It just wasn't on people's radars. And there can be differences in the drugs. Figure 2. Percentage Weight Loss and Categorical Percentage Weight Loss at 3 and 6 Months. In SELECT, investigators were allowed to slow, decrease or pause treatment. Third, major differences existed between the respective trial protocols. Several reasons may explain the observation that the mean treatment difference was −12.5% in STEP 1 and −8.7% in SELECT. You know, they're concerned especially about these drugs increasing fat discrimination and stigma in society because now you can say, well, why don't you just take Wegovy, right? But is the popularity of drugs like Ozempic possibly eclipsing that movement? But I'm thinking about the body positivity movement and embracing all body sizes. And she says, like, obesity is a disease. I used to want an hourglass, but now I'm starving out my ass - terzepitide, semaglutide. In conclusion, this analysis of the SELECT study supports the broad use of once-weekly subcutaneous semaglutide 2.4 mg as an aid to CV event reduction in individuals with overweight or obesity without diabetes but with preexisting CVD. Indeed, in our first on-treatment analysis at week 208, weight loss was greater (−11.7% for semaglutide) compared with the in-trial analysis (−10.2% for semaglutide). The analyses of weight effects of the SELECT study presented here reveal that patients assigned to once-weekly subcutaneous semaglutide 2.4 mg lost significantly more weight than those receiving placebo. Individual changes in body weight with semaglutide and placebo were striking; still, 67.8% achieved 5% or more weight loss and 44.2% achieved 10% weight loss with semaglutide at 2 years, compared with 21.3% and 6.9%, respectively, for those receiving placebo. In the semaglutide group, 12.0% of patients achieved a BMI −2, which is considered the healthy BMI category, compared with 1.2% for placebo; per study inclusion criteria, no patients were in this category at baseline. The BMI category change reflects the superior weight loss with semaglutide, which resulted in fewer patients being in the higher BMI categories after 104 weeks. For personalized thyroid treatment plans and expert guidance, reach out to Dr. Anshul Gupta.Our approach focuses on holistic and sustainable methods to manage thyroid health and enhance energy levels. In one study including 1306 patients taking semaglutide, 2.4 mg, weight loss of approximately 6% was achieved by week 12 and 12% was achieved by week 28.18 Our results reflect similar weight loss outcomes within the same period, particularly for patients taking doses of 1.7 mg and 2.4 mg. This cohort study, conducted at a referral center for weight management, retrospectively collected data on the use of semaglutide for adults with overweight or obesity between January 1, 2021, and March 15, 2022, with a follow-up of up to 6 months. Missing data at the landmark visit, for example, week 104, were imputed using a multiple imputation model and done separately for each treatment arm and included baseline value as a covariate and fit to patients having an observed data point (irrespective of adherence to randomized treatment) at week 104. In the SELECT trial, patients did not enroll for the specific purpose of weight loss and received standard of care covering management of CV risk factors, including medical treatment and healthy lifestyle counseling, but without a specific focus on weight loss. Clinically meaningful weight loss was evident in the semaglutide group within a broad range of baseline categories for glycemia and body anthropometrics. ETD, estimated treatment difference; sema, semaglutide.Full size imageAmong in-trial (intention-to-treat principle) patients at week 104, weight loss of ≥5%, ≥10%, ≥15%, ≥20% and ≥25% was achieved by 67.8%, 44.2%, 22.9%, 11.0% and 4.9%, respectively, of those treated with semaglutide compared with 21.3%, 6.9%, 1.7%, 0.6% and 0.1% of those receiving placebo (Fig. 2a).You know, they're concerned especially about these drugs increasing fat discrimination and stigma in society because now you can say, well, why don't you just take Wegovy, right?Individual patient data will be shared in data sets in a deidentified and anonymized format.So we've seen in, you know, anecdotal reports and also in studies that the pharmaceutical companies have done that when they - when people stop taking these medications, they tend to regain weight.It's actually - you know, the name, you know, the jingle, that's all for diabetes.The phenotype of cardiometabolic disease but lower BMI (−2) may be one where reduction of excess abnormal and dysfunctional body fat does not require as much body mass reduction to achieve health improvement. However, weight-management medications that modify appetite can make attaining and sustaining clinically meaningful weight loss of ≥10% more likely12. Producing and sustaining durable and clinically significant weight loss with lifestyle intervention alone has been challenging11. Excess abnormal body fat, especially visceral adiposity and ectopic fat, is a driver of cardiovascular (CV) disease (CVD)3,4,5, and contributes to the global chronic disease burden of diabetes, chronic kidney disease, cancer and other chronic conditions6,7. The worldwide obesity prevalence, defined by body mass index (BMI) ≥30 kg m−2, has nearly tripled since 1975 (ref. 1). Main Outcomes and Measures They started studying this higher dose version for weight loss specifically. Emma Court has been reporting on Ozempic and this new class of weight-loss drugs for Bloomberg. Or that Oprah and Elon Musk are using a new class of drugs like Ozempic to lose weight. Continuous endpoints were analyzed using an analysis of covariance model with treatment as a fixed factor and baseline value of the endpoint as a covariate. Body weight was measured without shoes and only wearing light clothing; it was measured on a digital scale and recorded in kilograms or pounds (one decimal with a precision of 0.1 kg or lb), with preference for using the same scale throughout the trial. Second, the respective study populations were quite different, with STEP 1 including a younger, healthier population with more women (73.1% of the semaglutide arm in STEP 1 versus 27.7% in SELECT) and higher mean BMI (37.8 kg m−2 versus 33.3 kg m−2, respectively)14,21. Is the weight loss in SELECT less than expected based on prior studies with the drug? Potential contributors may include a possibility of higher drug exposure in lower BMI classes, although other explanations, including differences in motivation and cultural mores regarding body size, cannot be excluded. And when they do that, they have different effects in the body. But largely, when we're talking about this, like, Ozempic, Wegovy, these are drugs known as GLP-1s. So when we talk about these drugs, there are some newer versions that are now coming out with slightly different science. What are they actually doing to the body and the brain? But can you first tell us how these drugs work? Because it feels like everybody's on it. But there are also these social and economic equity issues at play here because only a fraction of the people in your reporting, you say, can benefit from actually having the means or access to them. And these drugs are supposed to be taken for the rest of your life, by the way. Our first on-treatment analysis demonstrated that those on-drug lost more weight than those in-trial, confirming the effect of drug exposure. Furthermore, both sexes, all races, all body sizes and those from all geographic regions were able to achieve clinically meaningful weight loss. The weight-loss trajectory with semaglutide occurred over 65 weeks and was sustained up to 4 years. For lower BMI classes, discontinuation rates are higher in the semaglutide group but not the placebo group. For lower BMI classes, discontinuation rates are higher in the semaglutide group but not the placebo group.Fig. The average percentage weight-loss trajectories with semaglutide and placebo over 4 years of observation are shown in Fig. Of note, in the lower BMI categories (−2 (overweight) and 30 to −2 (class I obesity)), the proportion of Asian individuals was higher (14.5% and 7.4%, respectively) compared with the proportion of Asian individuals in the higher BMI categories (BMI 35 to −2 (class II obesity; 3.8%) and ≥40 kg m−2 (class III obesity; 2.2%), respectively). In 12 weeks, weight loss of approximately 4% was achieved among patients taking the 1-mg dose, and weight loss of approximately 5% was achieved among those taking the 2.4-mg dose.21 In addition, weight loss at 28 weeks approached approximately 7% for patients taking the 1-mg dose and 9.6% for those taking the 2.4-mg dose. Hence, this study may be a stepping stone to demonstrating the effectiveness of semaglutide for patients aiming to lose weight. Our cohort experienced a wide range of weight loss responses to semaglutide at 3 and 6 months (eFigure 2 in the Supplement). Of 102 patients who were followed up for 6 months, 89 (87.3%) achieved weight loss of 5% or more, 56 (54.9%) achieved weight loss of 10% or more, 24 (23.5%) achieved weight loss of 15% or more, and 8 (7.8%) achieved weight loss of 20% or more (Figure 2). In our cohort of 175 patients, 94 (53.7%) had weight loss of at least 5% and 26 (14.9%) had weight loss of 10% or more at 3 months. Here in this prespecified analysis, we examined effects of semaglutide on weight and anthropometric outcomes, safety and tolerability by baseline body mass index (BMI). Categorical weight loss at 68 weeks for STEP trials 1–4 Percent initial weight loss at 68 weeks for STEP trials 1–4 In addition, the weight loss data of semaglutide use might be more representative of day-to-day clinical practice, including a more heterogenous patient population, compared with RCTs. When I first started writing about them, almost nobody was paying attention to the fact that Novo Nordisk had developed this highly effective weight loss drug, right? There have been recurring shortages of these diabetes and weight-loss drugs due to the, like, intense interest in this area of late. So we saw recently, WeightWatchers acquired a telemedicine company that prescribes drugs like Ozempic for weight loss. They can't just study these drugs for a couple of months or even a year. This plateau has been termed the ‘set point’ or ‘settling point’, a body weight that is in harmony with the genetic and environmental determinants of body weight and adiposity31. Asian individuals would probably benefit from weight loss and medication approaches undertaken at lower BMI levels in the secondary prevention of CVD. Taken together, all these issues make less weight loss an expected finding in SELECT, compared with STEP 1. Patients in the semaglutide treatment arm of STEP 1 were more likely to be exposed to the medication at the full dose of 2.4 mg than those in SELECT. Ozempic, which is the brand name for semaglutide, is an injectable prescription originally used to treat Type 2 diabetes. Bloomberg News reporter Emma Court explains how these so-called "miracle drugs" work, and discusses side effects, long-term impacts, and what it all means for the body positivity movement. In this video, Dr. Anshul Gupta, MD, shares a natural solution—a simple, powerful drink that’s just as effective as Ozempic for weight loss. Have you heard about Ozempic, the medication making headlines for its impressive weight loss results? The category ‘Other’ for CV inclusion criteria includes patients where it is unknown if the patient fulfilled only one or several criteria and patients who were randomized in error and did not fulfill any criteria. Trial design and participants In patients with type 2 diabetes and high CV risk, semaglutide at doses of 0.5 mg and 1.0 mg has been shown to significantly lower the risk of CV events20. Recently, weight-management medications, particularly those comprising glucagon-like peptide-1 receptor agonists, that help people achieve greater and more sustainable weight loss have been developed13. Remediating the adverse health effects of excess abnormal body fat through weight loss is a priority in addressing the global chronic disease burden. The trial protocol was designed by the trial sponsor, Novo Nordisk, and the academic Steering Committee. We suspect this may be the case and suggest further studies to explore this aspect of weight-loss physiology. The phenotype of cardiometabolic disease but lower BMI (−2) may be one where reduction of excess abnormal and dysfunctional body fat does not require as much body mass reduction to achieve health improvement. Perhaps persons with BMI −2 are closer to their settling point and have less weight to lose to reach it. And we're talking about the surge in popularity of new weight loss drugs like Ozempic, Wegovy and Mounjaro.You know, you should just lose weight on Wegovy, and then you won't be living in a big body anymore, right?Excess abnormal body fat, especially visceral adiposity and ectopic fat, is a driver of cardiovascular (CV) disease (CVD)3,4,5, and contributes to the global chronic disease burden of diabetes, chronic kidney disease, cancer and other chronic conditions6,7.Another serious limitation is the exclusion of patients who did not reach 3 months of follow-up, which might have resulted in an overestimation of the association of semaglutide with body weight.This study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline.The analyses of weight effects of the SELECT study presented here reveal that patients assigned to once-weekly subcutaneous semaglutide 2.4 mg lost significantly more weight than those receiving placebo.Studies with longer periods of follow-up are needed to evaluate prolonged weight loss outcomes.In the STEP 2 trial comparing 1 mg and 2.4 mg of semaglutide for patients with type 2 diabetes, similar weight loss trends compared with those in our study were seen. Studies with longer periods of follow-up are needed to evaluate prolonged weight loss outcomes. Weekly 1.7-mg or 2.4-mg semaglutide subcutaneous injections for 3 to 6 months. But, you know, we still don't - we're still not there yet in terms of saying these drugs make people healthier, period. You know, you should just lose weight on Wegovy, and then you won't be living in a big body anymore, right? That's performance artist Ari Dayan, and it's a satirical take on the use of these drugs, like Ozempic, to lose weight. We reported in the primary SELECT analysis that serious adverse events (SAEs) were reported by 2,941 patients (33.4%) in the semaglutide arm and by 3,204 patients (36.4%) in the placebo arm (P 21. For this study, we analyzed SAE rates by person-years of treatment exposure for BMI classes (−2, 30 to −2, 35 to −2, and ≥40 kg m−2) and provide these data in Supplementary Table 2. Among in-trial (intention-to-treat principle) patients at week 104, weight loss of ≥5%, ≥10%, ≥15%, ≥20% and ≥25% was achieved by 67.8%, 44.2%, 22.9%, 11.0% and 4.9%, respectively, of those treated with semaglutide compared with 21.3%, 6.9%, 1.7%, 0.6% and 0.1% of those receiving placebo (Fig. 2a). B,c, Percentage change in body weight for individual patients from baseline to week 104 for semaglutide (b) and placebo (c). The lifestyle counseling was not targeted at weight loss. Patients who were unable to tolerate dose escalation due to AEs could be managed by extension of dose-escalation intervals, treatment pauses or maintenance at doses below the 2.4 mg per week target dose. All patients provided written informed consent before beginning any trial-specific activity. Semaglutide 2.4 mg safely and effectively produced clinically significant weight loss in all subgroups based on age, sex, race, glycemia, renal function and anthropometric categories. Furthermore, the cardiometabolic benefits of weight loss are driven by reduction in the abnormal ectopic and visceral depots of fat, not by reduction of subcutaneous fat stores in the hips and thighs. Proportions of patients in the BMI categories at baseline and week 104 are shown in Fig. At week 104, 41.2% fell below the sex- and race-specific cutoff points for the semaglutide group, compared with only 18.0% for the placebo group (Fig. 3). Within the SELECT population with BMI −2 at baseline, 15.0% and 14.3% of the semaglutide and placebo groups, respectively, were below the sex- and race-specific WC cutoff points. A,b, Observed data from the in-trial period (a) and first on-treatment (b). There was no detectable difference in hepatobiliary or gastrointestinal SAEs comparing semaglutide with placebo in any of the four BMI classes we evaluated. Studies with greater sample sizes and longer periods of follow-up are further needed to support the effectiveness of semaglutide. Finally, using the EMR database might have increased susceptibility to coding errors and missing data during the data extraction phase. Moreover, some of the abstracted weights were self-reported, which might be not as accurate as clinic measurements (noncalibrated vs calibrated scales). Also, there is a possibility of recall bias because the dates of medication initiation and termination were reported by patients during patients’ visits or communications with their physicians and therefore may not be exact. However, patients who were lost to follow-up may have experienced adverse effects and discontinued the medication without reporting to the clinician. Cup Powerful Than Ozempic For Weight Loss And yet people are still gravitating to it for this other purpose as well. It's actually - you know, the name, you know, the jingle, that's all for diabetes. But, you know, even though you've seen the Ozempic commercials, these are Ozempic commercials for Ozempic for diabetes. We haven't seen - you know, usually the pharma industry spends a lot of money and invests a lot into getting the word out about these drugs. Was it with the approval of Wegovy, which is basically the same ingredient as Ozempic for weight loss? And so Novo Nordisk saw these improving amounts of weight loss. Ozempic is not technically approved for weight loss. BMI, body mass index; CI, confidence interval; CV, cardiovascular; CVD, cardiovascular disease; eGFR, estimated glomerular filtration rate; ETD, estimated treatment difference; HbA1c, glycated hemoglobin; MI, myocardial infarction; PAD, peripheral artery disease; sema, semaglutide. Overall, 97.1% of the semaglutide group and 96.8% of the placebo group completed the trial. The fit model is used to impute values for all patients with missing data at week 104 to create 500 complete data sets. Furthermore, the weight loss was sustained over 4 years during the trial. There is a plateau of weight that occurs after weight loss with all treatments for weight management. We excluded patients with a history of bariatric procedures (ie, surgical or endoscopic), taking other FDA-approved AOMs, or with an active malignant neoplasm or pregnancy. The Mayo Clinic institutional review board approved the study and waived the need for informed consent owing to its minimal-risk nature. Patients with a history of bariatric procedures, taking other antiobesity medications, and with an active malignant neoplasm were excluded. You know, and a lot of the time, like, we have seen medical treatments and pharmaceutical, you know, involvement in areas actually change the way conditions are perceived, right? We can't have them taken away from us because of this recurring weight loss frenzy. So it's not the most above the board source of getting weight-loss drugs, I would say. And so compounded drugs are, you know, pharmacy-made versions, and people have been buying cheaper versions of so-called Ozempic from these compounding pharmacies. Actually, lots of people take compounded drugs. And so I think it seems like people are like, OK, let's just use Ozempic then. But it's, you know, a lot of people think of these things as the same thing, even though they are different doses and they've been studied for different purposes and in different patient populations. So how did it go from, oh, it's helping diabetics lose weight as a side effect, to being the most sought-after weight-loss drug in the world? It's approved for diabetes, as you mentioned. And you saw companies like Novo Nordisk, which is, you know, widely considered the leader in this field - they were the first to bring a highly effective weight-loss drug to market. Once-weekly subcutaneous semaglutide 2.4 mg, a glucagon-like peptide-1 receptor agonist, is approved for chronic weight management14,15,16 and at doses of up to 2.0 mg is approved for type 2 diabetes treatment17,18,19. In SELECT, at 208 weeks, semaglutide produced clinically significant weight loss and improvements in anthropometric measurements versus placebo. In patients treated with semaglutide, weight loss continued over 65 weeks and was sustained for up to 4 years. The proportion (percentage) of weight loss seems to be less, on average, in the BMI −2 category relative to higher BMI categories, despite their receiving of the same treatment and even potentially higher exposure to the drug for weight loss30. This was also observed in Look AHEAD, a lifestyle intervention study for weight loss30. By 104 weeks, approximately 77% of SELECT patients on dose were receiving the target semaglutide 2.4 mg weekly dose, which is lower than the corresponding proportion of patients in STEP 1 (89.6% were receiving the target dose at week 68)14,21. First, SELECT was designed as a CV outcomes trial and not a weight-loss trial, and weight loss was only a supportive secondary endpoint in the trial design. Interestingly, at 2 years, a significant proportion of the semaglutide-treated group fell below the sex- and race-specific WC cutoff points, especially in those with BMI −2, and a notable proportion (12.0%) fell below the BMI cutoff point of 25 kg m−2, which is deemed a healthy BMI in those without unintentional weight loss. At 3 months, 175 patients achieved a mean (SD) weight loss of 6.7 (4.4) kg, equivalent to a mean (SD) weight loss of 5.9% (3.7%) (P P Figure 2). 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). She's a reporter for Bloomberg and has been reporting on Ozempic and the new class of weight loss drugs that are being touted as miracle drugs. Categorical weight loss at 68… Percent initial weight loss at… Theoretical and empirically supported mechanisms of action of semaglutide for obesity Moreover, we reported few moderate and severe adverse events (eg, nausea and constipation) that resulted in continuing to receive the same dose of medication or even discontinuing semaglutide. In our study, adverse effects were reported in approximately 50% of our cohort during follow-up. Considering the scarcity of AOMs, choosing the most suitable and individualized therapy is important.6 Retrospective studies comparing high doses of semaglutide (ie, 1.7 and 2.4 mg) with other AOMs are limited. These results may support the applicability of semaglutide in a less controlled environment, as previously proven in RCTs.18,19,20 Or we're seeing people who are willing to pay out of pocket, which is very expensive... We found that about four were adding - had added obesity drug coverage since 2021, which is when Wegovy became available. You know, the data varies, but we found that about three-quarters of private insurers typically don't cover these medications. But, yeah, how is this working out for people? So a lot of people - some groups of people are getting access to it but others are not. The findings of this cohort study suggest that semaglutide is clinically effective for weight loss at 3 and 6 months for people with overweight or obesity. In the STEP 2 trial comparing 1 mg and 2.4 mg of semaglutide for patients with type 2 diabetes, similar weight loss trends compared with those in our study were seen. This cohort study assesses weight loss outcomes of semaglutide at doses used in randomized clinical trials for patients with overweight or obesity. Nausea and vomiting were the most encountered adverse events (64 patients 36.6%), followed by diarrhea (15 patients 8.6%) and fatigue (11 patients 6.3%). Weight changes ranged between 3.6% and −14.3% at 3 months and between −0.6% and −29.1% at 6 months. Detailed information of the maximum dose reached by our cohort of patients is presented in eTable 2 in the Supplement. Mean values of fasting glucose, hemoglobin A1c, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides at baseline are presented in Table 1. 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. Discontinuations increased as BMI class decreased. Semaglutide is a glucagon-like peptide-1 receptor agonist that was recently approved by the US Food and Drug Administration for chronic weight management. This section collects any data citations, data availability statements, or supplementary materials included in this article. And we're talking about the surge in popularity of new weight loss drugs like Ozempic, Wegovy and Mounjaro. She's a reporter for Bloomberg and has been reporting on Ozempic and the new class of weight-loss drugs that are being touted as miracle drugs. We have seen, you know, indications that people's health may improve when they are on these drugs and they're losing weight.