Continuing weight loss of patients… Our results show a comparable effectiveness of IS and OS in T2DM patients with obesity or overweight. Notably, the 2.4 mg weekly injection of semaglutide has recently been approved by the US Food and Drug Administration (FDA) as of June 2021 (brand name Wegovy) for the chronic management of weight in adults with obesity or overweight and at least one weight-related comorbidity,26 providing a powerful new tool in the arsenal of obesity therapies. This site is intended for US patients only.HCT, OAD, MMM conceived the study; developed the methodology; synthesized the data and prepared the original draft.Mares et al. highlight semaglutide 2.4 mg as a new treatment option for adults with obesity or overweight .Conversely, studies have shown that both patients and healthcare professionals are reluctant to initiate GLP-1RAs 11, 12, despite the guideline recommendations and the health benefits of these therapies, particularly for patients in need of weight loss and those with low estimated glomerular filtration rate .Instead, it complements an overall healthy lifestyle approach including proper nutrition and physical activity.The IWRS generated the randomization list and assigned patients to the next available treatment according to the randomization schedule.For children aged 12 and up with obesity, along with a reduced-calorie diet and increased physical activity to lose weight and keep it offAnd it's working on an obesity pill, too. If you think you’re experiencing any of these issues, speak with a healthcare provider immediately. Many patients also find relief from mild nausea by sipping ginger tea or taking ginger capsules. All forms of GLP-1s carry the risk of some side effects. By and large, our study was considered to be the latest and most comprehensive systematic review of randomized controlled trials, which fully examined the weight loss effects of different dosages of semaglutide compared with placebo in obese or overweight patients without diabetes. “OASIS 1, a phase 3 trial, which examined the efficacy and safety of a higher, 50-mg dose per day of oral semaglutide, showed efficacy, with 15.1% weight loss versus 2.4% for placebo in patients with overweight and obesity, and also improved cardiometabolic risk factors. In conclusion, the present study, which evaluated oral semaglutide at a daily dose of 14 mg for the treatment of obesity in adults without diabetes, demonstrated substantial interindividual variability in weight loss response in a real-world setting. The study also estimated the hypothetical trial-product estimand, which estimates treatment effect assuming patients adhere to the treatment as assigned, resulting in a mean change in body weight of –16.6% for oral semaglutide and 2.7% for placebo (95% CI, –16.5% to –11.2%). The longest available efficacy data for semaglutide as an AOM are derived from the STEP 5 trial, showing a durable, sustained, substantial weight loss over a 2-year study duration with mean reduction in body weight of 15.2% in semaglutide group compared to 2.6% in placebo group (16). This is mirrored by similar analyses carried out on trials with other GLP‐1RAs. GI AEs were generally reported at higher rates with semaglutide than with comparators, and higher rates were observed in the subgroups with comparatively lower, rather than higher, baseline BMI (Table 2). Weight loss was generally more pronounced in subjects who experienced nausea or vomiting compared with those who did not experience such events. Overall, nausea and vomiting events were mostly transient, with a median duration of between 1 and 8 days with the semaglutide 0.5 and 1.0 mg and comparator groups. In Slovenia, access to effective obesity medications remains limited and pharmacological obesity treatment is not reimbursed. A weight loss of at least 5% is considered clinically significant, while a 15% reduction effectively improves most obesity-related complications and conditions. The primary goal of obesity treatment is to improve health, with weight monitoring serving as a proxy indicator of treatment efficacy. Of the 93 subjects recruited, 82 (88%) were receiving oral semaglutide at a dose of 14 mg after one year. Semaglutide, liraglutide, dulaglutide, tirzepatide, and exenatide demonstrated mean weight loss reductions of 4.81 kg, 2.81 kg, 4.03 kg, 9.7 kg, and 1.9 kg, respectively, with high rates of minimal to moderate-severity AEs. Nine studies with 5,445 patients whose mean age was 60.01 years (55.5-70) and mean follow-up of 32.5 weeks (4-58.7) were included. A narrative synthesis and meta-analysis using SPSS program version 29 were performed to analyze the differences in weight loss between cohorts. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are antidiabetic drugs that have a recognized effect on weight loss. Obesity places patients at higher risk for numerous problems, including prediabetes, type 2 diabetes mellitus (T2DM), hypertension, metabolic syndrome, cardiovascular disease, and nonalcoholic fatty liver disease. Due to its popularity, the medication is on backorder with no definitive date of availability. Other effects, some rare, include medullary thyroid carcinoma. GI symptomsGI symptoms, the most frequently reported adverse effect, results from semaglutide’s delayed gastric emptying (the drug’s action on appetite regulation). Gallbladder diseaseThe unclear association between semaglutide and gallbladder disease requires further investigation. Mental illness and obesity share not only pathogenic pathways involving the immune and endocrine system, but also coping behaviours and sociodemographic factors (50). Finally, future research efforts should also be directed towards the combination of semaglutide with, rapidly evolving, endoscopic bariatric therapies, such as intragastric balloons or endoscopic sleeve gastrectomy (48). Another potential, albeit untested yet, therapeutic application of semaglutide is that of neoadjuvant pharmacotherapy prior to bariatric surgery. Due to their exclusion from the STEP programme, there is lack of high-quality evidence about semaglutide use in post-bariatric surgery populations. Gastroparesis symptoms, such as nausea, vomiting, and fullness after eating, are very similar to common semaglutide side effects. This was compared to people taking Contrave (bupropion / naltrexone), a weight-loss pill. And there’s a chance you could have an allergic reaction to semaglutide if you’ve had a reaction to a medication in the same class. Don’t use oral or injectable semaglutide if you’re allergic to any of their ingredients. Taking medications that cause you to get rid of excess water, such as diuretics (water pills), may also increase your risk. At Minimal, we believe in a tailored approach to wellness, ensuring that our clients are well-informed about the medications they are using, including Wegovy. While serious side effects are rare, they can include pancreatitis and thyroid tumors, making it essential to have a thorough conversation with healthcare providers to evaluate individual health profiles. Ongoing research into the GLP-1 hormone continues to reveal its potential in transforming obesity treatment. This targeted impact on appetite is a promising development for those navigating their weight loss journey. Consistent with observations for the GLP-1RA class as a whole, severe hypoglycemic episodes were found to be rare in all the PIONEER studies (Table 4). An exposure-response analysis of data from the SUSTAIN and PIONEER programs for s.c. Gastrointestinal AEs were reported in similar proportions of patients in the s.c. As expected, gastrointestinal AEs also occurred on treatment with GLP-1RA comparators (Table 4). AE adverse event, BG blood glucose, CV cardiovascular, GI gastrointestinal, HbA1c glycated hemoglobin, NR not reported, SGLT2i sodium-glucose co-transporter-2 inhibitor, SU sulfonylurea, T2D type 2 diabetes, TZD thiazolidinedione Semaglutide: A Game-Changer for Weight Loss Management The GLP-1-based medications prescribed vary depending on the medical judgment of the provider. During your first appointment, your provider will discuss your health goals, review your medical history, order any necessary lab tests, and may order a prescription medication if deemed appropriate. There are patients that may require maintenance therapy even if their BMI drops below 25 and your healthcare provider will determine if this option is right for you. In STEP 1–4, the trial duration was 68 weeks, and weight loss seemed to plateau, on average, close to the end of each trial. An observational, non-interventional survey study, called SELECT-LIFE, will examine the long-term effects of participants taking part in the SELECT trial. Rare cases of acute pancreatitis, hypoglycemia, acute kidney injury, diabetic retinopathy in patients with type 2 diabetes, angioedema and anaphylaxis have been reported with semaglutide. Gastrointestinal effects were the main adverse-event-related cause of drug discontinuation, accounting for 3.4 to 4.5% of discontinuations in the semaglutide group versus 0 to 1% in the placebo group. For example, in STEP 3, the median event duration of nausea was 5 days in both groups, vomiting was 2 days in both groups, diarrhea was 3 days in both groups, and constipation was 27 days with semaglutide vs 16 days with placebo.(36) The proportion of patients with premature discontinuation because of adverse events was 5.9–7.0% in the semaglutide groups and 2.9–3.5% in the placebo groups. But certain semaglutide side effects, such as dehydration, can result in headaches. And facial fat loss is one potential effect of fast and significant weight loss. Ozempic isn’t approved for weight loss, but some people using it lose weight. They may need to adjust your medications or check for an underlying cause. Fatigue is a common side effect of Wegovy, reported by 11% of people using it in clinical trials. The PIONEER trials compared oral semaglutide with placebo or active comparators in a wide range of patients and background therapies and reported the efficacy and safety of oral semaglutide. The 24-week treatment with oral semaglutide ameliorated glycemic control with reduction of body fat but not muscle mass in Japanese patients with type 2 diabetes. We evaluated the effect of 24-week treatment with oral semaglutide on body fat and muscle mass in 25 Japanese patients with type 2 diabetes. A potential limitation of oral semaglutide is the need to dose patients in a fasted state upon waking and 30 min before consuming food, drink, or other oral medications. The impact of age at baseline on the efficacy and safety of oral semaglutide was also examined in an exploratory analysis, and this showed that there were greater effects of oral semaglutide versus comparators on HbA1c and body weight in patients with T2D regardless of age group (67]. It has the same ingredient — semaglutide — that's in Wegovy, Ozempic and also in Rybelsus, the company's Type 2 diabetes pill that was approved in 2019. "With today's approval of the Wegovy pill, patients will have a convenient, once-daily pill that can help them lose as much weight as the original Wegovy injection." Millions of people use injectable drugs like Wegovy to reach a healthier weight. An injectable may be preferable if larger average weight loss is the priority. A realistic expectation is modest, steady weight loss rather than immediate dramatic change. This program included five trials primarily focused on comparing 2.4 mg, once-weekly, subcutaneous semaglutide with placebo treatment.11–15 This trial program did not compare semaglutide with other antiobesity medications currently on the market. In a similar study, Pioneer 6 conducted by Husain et al. to study the cardiovascular safety of oral semaglutide 14 mg showed there was -4.2 kg change in body weight from baseline in semagltuide group vs -0.8 kg in the placebo group . Blundell et al. conducted randomized, double‐blind, placebo‐controlled, two‐period crossover trials, in 30 subjects with obesity to study the effects of 12 weeks of treatment with the therapy of once‐weekly subcutaneous semaglutide . Oral semaglutide treatment improved the fasting lipid profile from baseline and reductions in total cholesterol were statistically significantly greater with the oral semaglutide 7-mg and 14-mg doses compared with placebo. Fewer subjects required the use of rescue medication while taking oral semaglutide with only 4% of subjects needing rescue medication compared with 10% of subjects taking placebo throughout the duration of treatment. However, if the AEs are problematic, the investigators could reduce the dose and the dose escalation was resumed once the symptoms were diminished or resolved. If AEs were manageable, dose escalation was continued as per the given schedule. If required, the patient can be on the same dose even for more time so that patient can tolerate the dose. GLP-1RA should be started with a lower dose of 3 mg and then accelerate the dose after 1 month as per recommended dosing conditions. GI side effects are usually transient in nature and can be managed by proper patient counselling. Your doctor may talk to you about other GLP-1 medications, like tirzepatide (Mounjaro®, Zepbound®). In other words, these medications aren’t simply correcting a “bad” behavior by lowering your appetite and causing you to eat less. It’s a dysfunction of the normal pathways that regulate our body weight or, more specifically, our body fat. Coverage for Wegovy and other weight-loss medications varies by plan. As demand for medical weight loss therapies continues to grow, healthcare providers are increasingly focused on delivery formats that support patient adherence, consistent dosing, and improved performance. Semaglutide has become a cornerstone treatment for type 2 diabetes and chronic weight management. Timelines vary widely; clinical studies report population-average outcomes over measured study periods, which do not predict individual results. Do not change, adjust, or discontinue any medications or prescribed treatments without your physician's guidance and approval. Despite this, the present findings suggested that semaglutide may be a more favorable treatment option for patients with T2DM requiring weight management and glycemic control. The current sensitivity analysis identified that the exclusion of one study could significantly impact the overall results of weight loss data. Additionally, our strict inclusion criteria, which required randomized controlled trials with specific outcome measures such as glycemic control and weight loss, further narrowed the range of eligible studies. The sensitivity analysis results showed that removing one study (15) had a substantial effect on the overall effect size of the weight loss data and the statistical significance of the meta-analysis. In direct connection with these findings, Andreadis et al (25) found that compared with dulaglutide, semaglutide 1 mg was more effective at lowering body weight. Expected Weight Loss Outcomes Discrepancies may also stem from the shorter follow-up duration for the semaglutide group as this may have impacted the final body weight and HbA1C.Tell your health care provider if you are or plan to become pregnant.Patients will need to understand that, following the first year of treatment, continued use of semaglutide will help them principally in maintaining their lost weight rather than in losing additional weight (which many will desire because they will still have excess weight).The length of time semaglutide is used for weight loss can differ, but it is generally prescribed for a designated treatment period.These two studies suggest the possible benefits of long-term (indefinite) treatment with semaglutide (or other medications) to facilitate the maintenance of lost weight.These medicines work by copying a natural hormone in the body called GLP-1, which helps control blood sugar and appetite.Even for the older demographic, representing 39% of those with diabetes, the ease of oral administration could be beneficial.The authors thank the participants, investigators and site staff who were involved in the STEP 1 trial.Its highest dose, 2.4 mg once weekly, is necessary for some people to continue losing steady weight, but not all need to go up to it to see results. However, in the present study, we did not check daily exercise in the patients. In fact, a recent study showed that GLP-1 enhances insulin-mediated whole-body glucose uptake in the glucose clamp study of human subjects . Thus, we speculate that all patients in the present study may decrease daily consumption of diet. Although the study period was shorter and the analysis method of body composition was different, the results were consistent with the present study. The right side of the body PhA (R-PhA), the left side of the body PhA (L-PhA), and the ECW/TBW were unchanged during the study period. Is semaglutide (SGT) effective for weight loss? Some studies also revealed a dose-dependent effect of the therapy in those with poorly controlled diabetes. The Pioneer 6 trial ran for 15.9 months with 3183 patients, was a randomized, double-blind, placebo-controlled trial . We used 12 randomized clinical trials (RCTs) in our study and assessed the risk of bias using the Cochrane Risk of Bias tool (Figure 3). The articles were screened based on the title and abstract related to semaglutide and obesity treatment. Some tout a daily semaglutide pill as a game-changer for weight-loss treatment. In addition, participants in the semaglutide group with 15% or more vs. less than 15% weight loss had greater reductions in systolic BP (–10.1 mm Hg vs. –4.1 mm Hg), diastolic BP (–4.3 mm Hg vs. –1.1 mm Hg), C-reactive protein (0.34 mg/L vs. 0.74 mg/L), non-HDL cholesterol (0.9 mg/dL vs. 0.96 mg/dL) and triglycerides (0.73 mg/dL vs. 0.87 mg/dL). More participants with prediabetes at baseline achieved normoglycemia in the semaglutide vs. placebo groups at 64 weeks (71.1% vs. 33.3%). In the semaglutide group, those with 15% or more vs. less than 15% weight loss had greater improvements in fasting serum insulin (0.63 pmol/L vs. 0.88 pmol/L), FPG (–0.6 mmol/L vs. –0.3 mmol/L) and HbA1c (–0.4 percentage points vs. –0.2 percentage points). “One of our goals in treating with obesity medication is improving metabolic health parameters,” Domenica Rubino, MD, founder and director of the Washington Center for Weight Management and Research, said during a presentation at ObesityWeek. Social media’s ability to amplify public awareness of certain medications can result in increased demand, which can lead to drug shortages. Later that week, an advertisement appears on Ms. Adams’ social media feed promoting telehealth services and “home delivery of generic semaglutide.” However, these trials didn’t include patients with a history of pancreatitis. Thus, gastrointestinal adverse reactions should not be considered as a determining factor when selecting different formulations of semaglutide.This review synthesizes findings from multiple clinical trials, highlighting the impact of semaglutide on weight loss, metabolic parameters, and overall health outcomes in non-diabetic populations.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.For years, people have been trying all sorts of methods and medications in search of the perfect weight loss solution.Doctors may recommend it for people who need to lose weight for health reasons, even if they do not have diabetes. Figure 5. Effect of semaglutide on body weight compared to tirzepatide. In comparison to insulin treatment, semaglutide was found to significantly reduce the risk of first-time Alzheimer's disease (AD) diagnosis.6 Therefore, semaglutide could also play a significant role in delaying or preventing AD in the diabetic population. More research is required in the future to elucidate how semaglutide may be having these effects. Existing research has indicated the effectiveness of semaglutide in improving brain health and reducing the risk of cardiovascular events in the diabetic population. The global economic burden of obesity and subsequent weight loss interventions can not be understated with both medication and bariatric surgery. Although GLP-1 RAs have been shown to reduce weight, the effect on overall body composition is unclear in patients with obesity. Thus, increased leptin concentrations are correlated with decreased body weight, but elevated levels of leptin can be found with increased body fat levels seen in patients with obesity, suggesting an endogenous resistance to leptin . Thus, semaglutide’s superior weight loss has been theorized to be a result of improved metabolic activity via neurohumoral pathways and decreased compensatory downregulations of energy expenditure . Rubino et al. in STEP 8 also found a statistically significant improvement in weight loss with semaglutide compared to liraglutide, with averages of 15.8% and 6.4%, respectively. There have been cases of pulmonary aspiration in patients undergoing surgery due to delayed gastric emptying resulting in resident gastric content. Although this is a unique case, there is a need to understand if there is an association of four year semaglutide use with life threatening pancreatic complications, compounding risk factors and the mechanism by which it could occur. Diabetic Retinopathy (DR) is a microvascular complication of diabetes mellitus due to damage to the retina. There is no consistent, effective therapy for NAION other than discontinuation of semaglutide. After taking the medication once daily for 6 weeks, people in the study were able to perform better on an oral glucose tolerance test (OGTT). A phase 2 study found that the medication helps improve glucose tolerance in adults with prediabetes. At the highest dose, people lost about 11% of their body weight on average over 72 weeks (nearly 17 months). However, the absolute numbers remain very low, and differences were not statistically significant across pooled data. Semaglutide activates GLP-1 receptors in the body, boosting insulin release when blood sugar rises, suppressing glucagon, and delaying stomach emptying for prolonged fullness. Still, the FDA includes warnings in prescribing information, and patients should stay vigilant for symptoms. If lapsing in therapy, restart at lower doses to rebuild tolerance. Wait a week after the last dose to avoid overlap. Going the other way, begin semaglutide at a mid-level like 0.5-1 mg. Below, we cover 19 semaglutide side effects and how to manage them. Animal studies found an increased risk of thyroid C-cell tumors with semaglutide. This is the FDA’s strictest warning for medications. Semaglutide belongs to a class of medications called glucagon-like peptide-1 (GLP-1) receptor agonists. Although rare, some serious side effects have been linked to treatment. Semaglutide for Weight Loss: How It Works and Compares to Other Weight-Loss Medications A greater number of patients in the semaglutide 3- and 7-mg groups achieved an HbA1c 18] Gastrointestinal AEs were the most frequent AEs to cause premature discontinuation. The inclusion criteria were patients on baseline medication of metformin (≥1500 mg or maximal tolerated) for at least 90 days and HbA1c between 7% and 10.5%. The duration of diabetes was 3.5 years, body mass index (BMI) 31.8 kg/m2 and mean HbA1c 8.0%. What are side effects of Ozempic? Rubino et al. investigate the effects of continued semaglutide treatment versus placebo on weight loss maintenance in adults with overweight or obesity. To assess the comparative effectiveness of semaglutide, studies comparing it to a placebo, other pharmacological weight loss treatments, behavioral interventions, or surgical interventions will be included. These studies also highlighted the safety of semaglutide, with O'Neil et al. noting that it was generally well tolerated and led to clinically relevant weight loss compared to placebo . As the industry knows, demand for medical weight loss therapies is on the rise. The needle-free delivery format supports greater treatment flexibility and reliability as weight-management care expands into sustained, scalable models. Structure Therapeutics reports positive topline data from ACCESS program for its once-daily oral small molecule GLP-1 receptor agonist, aleniglipron. Eli Lilly expects US FDA approval for oral obesity drug in March 2026. Viking Therapeutics' weight-loss tablet shows promise in small study. How to Use Ozempic Across all published trials,semaglutide demonstrated a statistically significant greater percent decrease inweight from baseline and a greater likelihood of patients losing ≥5% of their bodyweight when compared with either placebo or liraglutide.RFK contributed to the conduct of the trial, data collection, analysis and interpretation and manuscript development.Maintaining your weight loss after achieving your goals is equally important.KKo contributed to the data analysis and interpretation and manuscript development.The results indicated that both subcutaneous and oral formulations of semaglutide were effective in promoting weight loss, with subcutaneous administration often yielding greater results.In those with diabetes, taking Wegovy® with insulin or a sulfonylurea can increase the risk of low blood sugar.The study showed that Ozempic reduced the risk of kidney disease progression and significantly lowered the risk of cardiovascular death. These pills offer a needle-free way to harness the benefits of semaglutide — a medication proven to support weight loss and regulate blood sugar. Studies and guidance will be needed to help providers and patients select an appropriate obesity treatment medication. These novel medications will provide patients and providers with additional choices for effective weight management strategies. Furthermore, the absence of structured lifestyle intervention following semaglutide withdrawal contrasts with the continuation of lifestyle intervention in other withdrawal trials (including in STEP 4)13, 14, 15 and may also have contributed to the trajectory of weight regain. Few participants with normoglycaemia at baseline had progression to prediabetes at week 68 or week 120, in either of the semaglutide or placebo arms (Figure 3). Changes in body weight in the subgroup of participants who shifted from prediabetes at baseline to normoglycaemia at week 68 and then reverted to prediabetes by week 120 are shown in Figure 1D and Table S4. In the study, oral semaglutide exposure was approximately two-fold higher in the 40-mg group vs the healthy male individual oral semaglutide 20-mg group with similar results in the group of male individuals with T2DM. More subjects in the oral semaglutide group experienced GI disorders and headache compared with those in the placebo group with 15% in the oral semaglutide group vs 4% in the placebo group reporting headaches and 14% in the oral semaglutide vs 13% in the placebo group reporting GI disorders. Within each dose group, subjects were randomized to receive either oral semaglutide or placebo containing matching amounts of SNAC. The single-dose study utilized varying combinations of SNAC and oral semaglutide (2–20 mg) to determine the amount of SNAC that provided the largest systemic absorption of oral semaglutide. Benefits were also observed in patients with more advanced T2D receiving background insulin (PIONEER 8). All trials shown here included a 2-week screening period and 5-week follow-up period (for those not continuing into the extension phase in PIONEER 7) Overview of the design and baseline patient characteristics from the PIONEER trial program The comparators in the PIONEER program were placebo (PIONEER 1, 4, 5, 6, and 8), empagliflozin 25 mg (PIONEER 2), sitagliptin 100 mg (PIONEER 3 and 7), liraglutide 1.8 mg (PIONEER 4) and 0.9 mg (PIONEER 9), and dulaglutide 0.75 mg (PIONEER 10). The authors concluded that the changes in exposure observed for furosemide and rosuvastatin are unlikely to be clinically relevant . Novo Nordisk does NOT sell semaglutide to any entities for use in compounding. Novo Nordisk is the only company in the United States with FDA-approved products containing semaglutide, identified under the trade names Rybelsus®, Ozempic®,and Wegovy®. Compounded semaglutide is NOT reviewed by the FDA for safety, efficacy or quality. If a dose is missed, it should be skipped, and the next dose should be taken the following day at the usual time. Common side effects include nausea, vomiting, diarrhea, decreased appetite, and stomach pain. This broadened use offers an innovative approach to weight loss, providing an alternative for those who have not found success with traditional weight loss methods. The effectiveness in weight loss is enhanced when combined with lifestyle changes like a balanced diet and regular physical activity. The clinical section of the label also includes data on Wegovy® major adverse cardiovascular events (MACE) risk reduction, improvements in HFpEF-related symptoms and physical function, as well as pain reduction related to knee osteoarthritis.10 In the EU, Wegovy® is indicated as an adjunct to a reduced-calorie diet and increased physical activity for weight management in adults with a BMI of 30 kg/m2 or greater (obesity) or adults with a BMI of 27 kg/m2 or greater (overweight) in the presence of at least one weight-related comorbid condition. Unlike common semaglutide side effects like mild nausea, pancreatitis pain is typically severe and persistent. The FDA prescribing information for Wegovy and Ozempic lists acute pancreatitis as a possible post-approval adverse reaction, observed in clinical trials and reported voluntarily. These are often in people with other risk factors like obesity, diabetes, or gallstones. During treatment, greater improvements in cardiovascular risk factors were observed from week 0 to week 68 with semaglutide than placebo (Tables 2 and S1), which tended to be slightly larger in the ExAS than in the FAS (Table S2). When obesity pharmacotherapy users were excluded, changes in body weight (Figure 1C) were similar to the full ExAS (Figure 1A). Changes in body weight from week 0 to week 68 and from week 68 to week 120 for these subgroups are reported in Table S4.When obesity pharmacotherapy users were excluded, changes in body weight (Figure 1C) were similar to the full ExAS (Figure 1A). Mean changes in body weight from week 0 to week 120 in the semaglutide arm were similar across subgroups defined by baseline age tertiles (Table S4). Most participants were female (67.0%) and White (75.8%), with a mean age of 49.0 years, weight of 105.5 kg and BMI of 37.6 kg/m2. Demographic and clinical characteristics at baseline were generally well balanced across the two arms in the ExAS (Table 1). An additional 22 participants completed the end‐of‐trial visit via telephone or email contact. Subgroup analyses will examine the efficacy and safety of semaglutide across different demographic or clinical subgroups, including age, sex, baseline BMI, race or ethnicity, and the presence of obesity-related comorbidities. To capture the effects of semaglutide across diverse ethnic backgrounds, the review will include studies with participants from various ethnic groups. Additionally, studies must include both male and female participants to provide a comprehensive understanding of semaglutide's effects across the sexes. However, the studies also noted the importance of lifestyle interventions in conjunction with semaglutide treatment 18,19. This was supported by Aroda, who highlighted the consistent superiority of semaglutide in glycemic control and weight loss . A recently published meta analysis concluded that retatrutide led to the most weight loss among GLP-1-based treatments, but it also caused the most side effects.GLP-1 medications like Ozempic® have changed the way people approach weight loss.Older adults, those losing weight rapidly, or individuals with pre-existing low energy may notice it more.The mean follow-up was 47.5+10.9 months, and a total of 9495 participants (98.4%) completed the trial.Further, a better understanding of the phenotypes of participants who may be well suited for specific medications and of the effects of switching medications among non-responders would enhance our understanding of best practices for patient selection and management.In the PIONEER trials, oral semaglutide was shown to be well tolerated, including in patients with renal impairment or at high CV risk 50, 51, and the safety and tolerability profile was consistent with the GLP-1RA class 49, 54, 55.When combined with other factors like healthy eating and exercising, this can help people achieve their weight loss goals . Previously, the anti-diabetic agent glucagon-like peptide-1 receptor agonists (GLP-1RAs) liraglutide and semaglutide given by injection were reported to decrease fat with less effect on muscle in diabetic patients. But body weight reduction by energy restriction may simultaneously reduce both fat and muscle. Excessive body fat may be a major cause of insulin resistance and diabetes. We invite you to join us as we explore the science behind oral semaglutide and its role in achieving sustainable weight loss.Concerned about her health because of a family history of cardiovascular disease and diabetes, Ms. Adams discusses weight loss medications with her primary care provider.The Mayo Clinic institutional review board approved the study and waived the need for informed consent owing to its minimal-risk nature.A study in 26 healthy male individuals found that tablet erosion of oral semaglutide was slower with 50 mL versus 240 mL of water .This approach ensures the inclusion of diverse and relevant studies, enabling a thorough evaluation of semaglutide's effectiveness, safety, and broader health impacts.No increase in QT intervals or adverse cardiac events have been noted.30,76 Heart rate should be monitored in participants taking semaglutide.They can help determine if this treatment aligns with your specific health needs and goals. Rybelsus is meant to be used with healthy eating and exercise. These effects can make blood sugar levels more steady throughout the day. People with type 2 diabetes often have trouble with high blood sugar, especially after meals. STEP 1 was a 68-week randomized, placebo-controlled trial that assessed weight management in 1961 adults with a BMI of ≥30 kg/m2 (or ≥27 kg/m2 with ≥1 weight-related comorbidity) and without type 2 diabetes.(34) Participants were randomly assigned to once-weekly subcutaneous 2.4 mg semaglutide or placebo, against a background of individual lifestyle counseling sessions every 4 weeks. We then review data on the mechanism of action, weight-loss and cardiometabolic efficacy, and safety of semaglutide 2.4 mg/week for the treatment of obesity. Another medication in this class, semaglutide 2.4 mg administered subcutaneously once weekly, was approved by the FDA in 2021 as an adjunct to reduced calorie intake and increased physical activity for chronic weight management in adults with obesity (initial BMI≥30 kg/m2) or overweight (initial BMI≥27 kg/m2) with at least one weight-related comorbidity.(10) In this review we briefly examine the weight loss efficacy of liraglutide 3.0 mg/day. In the US, an estimated 53.5% of adults are eligible for a weight loss medication.(4) Five medications are currently approved for weight management in the US (liraglutide, orlistat, phentermine, naltrexone/bupropion, phentermine/topiramate, and semaglutide), three in Europe (liraglutide, orlistat, and naltrexone/bupropion) and one in China (orlistat). While Rybelsus is the only FDA-approved oral semaglutide tablet, there are several alternatives that offer similar (or even more flexible) weight loss benefits. If you’re ready to explore whether semaglutide or tirzepatide fits your PCOS profile, a physician-guided consultation is the safest place to start.Semaglutide belongs to a class of medications known as glucagon-like peptide-1 receptor agonists, or GLP-1 RAs.Weight management sees tirzepatide edging out with 20% loss average, semaglutide around 15-17%.The average placebo-subtracted weight loss for semaglutide was 12.7 kg.21 Semaglutide has generated much scientific, clinical, and public excitement and interest given these large weight losses.Additional strengths include the multinational setting and the high rates of trial completion.It’s most effective when someone is committed to ongoing healthy habits. By helping regulate blood sugar and suppressing appetite, it can support weight loss efforts in conjunction with a healthy diet and regular exercise. This is crucial because consistent medication is key to achieving and maintaining healthy blood sugar and weight levels. They can assess your individual circumstances, explain the benefits and drawbacks of each treatment, and guide you towards the best approach for effective weight management and diabetes control. For example, individuals with a busy lifestyle or those who struggle with self-injection might find oral semaglutide more appealing. Injectable semaglutide has been a game-changer for many, offering significant improvements in blood sugar control and weight loss. The GIP component may actually soften nausea for some patients. This can reduce the absorption of oral contraceptive pills. Tirzepatide significantly slows gastric emptying, especially during dose increases. This difference may be clinically meaningful. Cardiometabolic improvements seen from week 0 to week 68 with semaglutide reverted towards baseline at week 120 for most variables. An off‐treatment extension assessed for a further year a representative subset of participants who had completed 68 weeks of treatment. At week 68, treatments (including lifestyle intervention) were discontinued. Interpreted the data and wrote the manuscript. These effects together can lead to weight loss over time. Understanding the approved uses of each product helps patients and doctors choose the right treatment based on individual health needs. Some healthcare providers may prescribe Rybelsus for weight loss, even though it is not officially approved for that use. We categorized participants based on their weight loss percentages (≥5%, 10%, and 15%) and reported the proportions of individuals experiencing specific adverse effects at mild, moderate, or severe levels. The medication had been prescribed by endocrinologist involved in obesity treatment, with the participants’ consent and agreement. Our study was retrospective and observational, based on real-world data from clinical practice. Oral semaglutide (Rybelsus®) is currently approved for the treatment of adults with type 2 diabetes who have not achieved adequate glycemic control with non-pharmacological measures. The incidence of other AEs of special interest, including acute pancreatitis, malignant neoplasms, and diabetic retinopathy, was also low and was broadly similar between oral semaglutide and comparators 46–55. Hypoglycemia is an important consideration for any glucose-lowering therapy, and severe hypoglycemic episodes were found to be rare with oral semaglutide. As expected for a GLP-1RA, gastrointestinal disorders such as nausea, vomiting, and diarrhea were the most prevalent AEs seen with oral semaglutide 46–50, 52–55. Semaglutide 0.5 mg was similar to that seen with once-daily oral semaglutide 14 mg. Summary of efficacy in glycemic control across the PIONEER trials 43,44,45,46,47,48,49,50,51. The results of the PIONEER program regarding HbA1c and weight reduction are each presented in Table 1 and Table 2. The program included 10 trials, eight of which were global and two of which were solely undertaken in Japan. SNAC promotes the absorption of semaglutide across the gastric mucosa in a time- and concentration-dependent manner, which is totally reversible. Oral semaglutide must be co-formulated with the absorption enhancer SNAC in order to be absorbed. For fast relief, your healthcare team may suggest an OTC antacid. Some people experience acid reflux symptoms while taking semaglutide, which can include burping or belching. Talk to your healthcare team if your fatigue isn’t improving or if it’s severe. These can include dips in your blood sugar levels, less energy from reduced food intake, and dehydration from the GI side effects. Results of analyses of the confirmatory and selected supportive secondary endpoints for the trial product estimand, are provided in Supplementary Table 1. The treatment policy estimand assesses treatment effect regardless of treatment discontinuation or rescue intervention; see Extended Data Fig. Efficacy was assessed among all randomized participants regardless of treatment discontinuation or rescue intervention. Time will tell if this agent will also receive a cardiovascular indication and how it will be incorporated into routine clinical practice. In our opinion, this is a welcome addition and provides an additional option for patients and providers. Based on the availability of baseline and at least one follow-up measurement, 320, 260, 155, 200, 155, and 297 patients were included in the analyses of HbA1c, body weight, TC, LDL, HDL, and BP, respectively. Analyses were adjusted for age, sex, T2D duration, semaglutide dose, baseline endpoint level, index year (to account for reimbursement policy changes), and concomitant anti-diabetic treatment. Ultimately, the commercialization of oral semaglutide is "contingent on portfolio prioritizations and manufacturing capacity," Novo Nordisk said in a statement. Wang W, Volkow ND, Berger NA, Davis PB, Kaelber DC, Xu R. Association of semaglutide with risk of suicidal ideation in a real-world cohort. Can neuropeptides treat obesity? Lucas E, Simmons O, Tchang B, Aronne L. Pharmacologic management of weight regain following bariatric surgery. This suggests that the present conclusions depend on including all studies and that one or more studies may have an undue influence on the overall estimate. Although random-effects model was used to account for heterogeneity, it is important to acknowledge that some residual heterogeneity may remain, affecting the precision of the estimates. Additionally, the quality of the included studies was variable, with some studies being of lower quality. The PIONEER 12 study is evaluating the efficacy and safety of oral semaglutide compared to sitagliptin in subjects with T2DM with an HbA1c of 7–10.5% treated with metformin . The most frequently reported GI events were constipation and nausea and the percentage of subjects who discontinued treatment because of AEs was similar between groups with 3–6% of subjects treated with oral semaglutide compared to 3% of subjects treated with dulaglutide . Glycosylated hemoglobin A1c below 6.5% was achieved by 21%, 43%, and 58% of people receiving treatment with oral semaglutide 3 mg, 7 mg, and 14 mg, respectively, compared with 41% of people treated with dulaglutide 0.75 mg. An open-label, 52-week randomized study completed in Japan, PIONEER 10, compared the safety, tolerability, and efficacy of oral semaglutide 3 mg, 7 mg, and 14 mg to subcutaneous dulaglutide 0.75 mg. Along with the development of novel agents, recent guidelines stress the patient’s coexisting diseases and risk factors before glycemic control, recommending medications with cardiovascular and renal benefits over those with glycemic control 2,3,4. GLP-1 receptor agonist (GLP-1RA) mimics the action of endogenous GLP-1, consequently reversing hyperglycemia and causing weight reduction, demonstrating its efficacy as an antidiabetic and antiobesity agent. No datasets were generated or analysed during the current study. They’ve become a game-changer for many people, offering real, sustained weight loss when lifestyle changes alone haven’t been enough. More and more people are turning to them to lose weight and improve their health. “We believe this is the most affordable self-pay price to date for a GLP-1 for weight loss,” the spokesperson said. “I expect that the effective doses of oral Wegovy will be much more expensive than the advertised $149, unfortunately. Unlike the injectables, which enter the bloodstream directly, the pills are broken down in the stomach, which means “the oral doses have to be much, much higher” than the Wegovy injections, which cap at 2.4 mg, McCoy explains. Data for the 82 completers are presented in the left column, and data for the 11 non-completers in the right column. Table 1 presents the baseline demographic and clinical characteristics of all participants, while Table 2 presents the differences in assessed parameters and their significance between the baseline and the one-year follow-up in 82 completers. We compared the baseline characteristics of the subgroups of completers and non-completers. “The fundamentals of obesity management will always be changes to diet and exercise,” Dr. Surampudi says. Since then, additional studies have shown similar results. Participants who incorporated only lifestyle changes lost about 2.4% of their weight. Many prescribe other brands of semaglutide, such as Ozempic and Rybelsus, off-label (using a drug that is FDA-approved for a different reason). One role of GLP-1 is to prompt the body to produce more insulin, which reduces blood sugar (glucose). The estimated end results at 68 weeks were mean change in body weight of −14.9% with 2.4 mg semaglutide, as compared with −2.4% with placebo . Mean body weight in the semaglutide group, as compared with the placebo group, was 2.9 kg lower in the group receiving 0.5 mg and 4.3 kg lower in the group receiving 1.0 mg . Sustain 6 trial conducted by Marso et al. at 230 sites in 20 countries assigned 3297 patients with type 2 diabetes who were on a standard-care regimen to receive once-weekly subcutaneous semaglutide (0.5 mg or 1.0 mg) or placebo for 104 weeks . In the trial, 412 patients were randomized to receive once-daily oral semaglutide 14 mg and 410 patients received empagliflozin 25 mg for 52 weeks . Many patients with T2DM are hesitant to move to treatment with injectable medications but cannot achieve target HbA1c levels with previously available oral medications alone. It is acceptable to inject these in the same body area, but the shots should not be right next to each other. Keep track of where you give each shot to make sure you rotate body areas. Use a different body area each time you give yourself a shot. If you will be using semaglutide at home, your doctor will teach you how the injections will be given. The cardiovascular benefits of semaglutide are attributed to several mechanisms beyond weight loss.11 These include reductions in blood pressure, blood lipids, and inflammation, as well as direct effects on the heart muscle and blood vessels.7,11 Understanding semaglutideHow semaglutide aids weight lossBeyond weight lossSafety and side effectsSemaglutide and weight managementReferencesFurther reading If you're considering using semaglutide for weight loss, it's important to consult a healthcare provider. However, semaglutide is not for everyone and is only one of many ways to achieve healthy, lasting weight loss. In the ever-evolving landscape of weight-loss medications, semaglutide has emerged as a groundbreaking option. Adverse events leading to discontinuation occurred in 7% of the oral semaglutide group vs. 6% of the placebo group. The trial included a 12-week dose escalation and a seven-week off-treatment follow-up, spanning 71 weeks with 64 weeks on therapy. Side effects, primarily gastrointestinal, were consistent with other GLP-1 medications and led to discontinuation in only about 5 percent of participants. With semaglutide, at least we now have a clearer picture of real-world adherence, coverage patterns, and what happens when patients stop because of cost or side effects. In PIONEER 5 and 8 in advanced T2D, the frequency of patient-perceived hyperglycemia was significantly lower in the oral semaglutide group than in the placebo group (26, 31). In PIONEER 7, change from baseline to week 52 in DTSQ scores for satisfaction with treatment, convenience and flexibility of treatment, and total treatment satisfaction appeared similar for oral semaglutide and sitagliptin despite the specific dosing instructions needed with oral semaglutide (33). There were no differences in treatment satisfaction between oral semaglutide and liraglutide 1.8 mg. In SUSTAIN 7, improvements in overall treatment satisfaction were generally similar between semaglutide and dulaglutide, irrespective of weight loss or glycemic control. With oral semaglutide, similar HbA1c reductions were seen as with once-daily liraglutide 1.8 mg when patients were on a background of metformin ± an SGLT2i in PIONEER 4 (–1.2% vs. –1.1%) (30). One of the most important findings in recent research is that tirzepatide improves insulin sensitivity more per pound lost than semaglutide. It helps your body handle energy, insulin, and fat differently. For many patients, this alone is life-changing. Overall, 6 patients (5.7%) experienced an adverse effect (AE) related to semaglutide during the study period, 2 patients (16.7%) in the oral group and 4 patients (4.9%) in the injectable group. Oral SG, oral semaglutide; Inj SG, injectable semaglutide; GLP-1, glucagon-like peptide; T2D, type 2 diabetes; SGLT-2, sodium-glucose cotransporter-2; HbA1C, hemoglobin A1C; Baseline, 3 months prior to initiation of therapy Patients were placed into 1 of 4 groups (ie, oral 7 mg, oral 14 mg, injectable 0.5 mg, and injectable 1 mg) based on the highest dose and which formulation of semaglutide they received during the study period and stayed in the assigned group regardless of whether or not the semaglutide dose was reduced. Higher doses used for weight loss show more reports compared to lower diabetes doses. Achieved 20.7% weight loss in the STEP UP obesity trial, and 18.7% regardless of treatment adherence. Wegovy (semaglutide) and Mounjaro (tirzepatide) are medications that can both cause significant weight loss. Semaglutide also causes weight loss by suppressing appetite. Those who took 25 mg and 14 mg lost about 14.8 pounds and 10 pounds, respectively.Over the course of the trial, researchers took note of side effects. According to the American Diabetes Association, most adults with diabetes need to have an A1C that is less than 7% to be considered healthy. “Whereas, the higher doses that are really good for weight reduction. Glucagon-like peptide-1 (GLP-1) receptor agonists, such as semaglutide, have granted patients more control in lowering of blood sugar. 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 Dietary changes and behavior modification with regular exercise may help maintain ideal body weight.18–20 Specifically, a reduction in caloric intake and a rise in the physical movement are the cornerstones of a bodyweight management program. 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. Hashmi founded the nonprofit organization SelfPrinciple.org to provide accessible and accurate health, nutrition, and wellness information to the public. Sean Hashmi, MD, is an experienced nephrologist and obesity medicine specialist based in Southern California. As prescription drugs go, semaglutide and tirzepatide are relatively new, so there’s a lot we still don’t know about them. What side effects do you need to watch for and how will they be managed? How will this change your current medicines if you have diabetes? Which trial results are most relevant to someone like you? The characteristics of patients contained the total number, gender, age, body weight (BW), body mass index (BMI), waist circumference (WC), and proportions with or without comorbidities at baseline.Gradual dose increases prevent overload.Participants who were given oral semaglutide began with 3 mg and the dose was gradually raised every 4 weeks until the goal dose was reached .Finally, concerns about the possible association of semaglutide-induced weight loss with sarcopenia and the loss of bone density should be addressed, and if needed, strategies should be developed to ameliorate these unwanted effects.Furthermore, oral semaglutide plasma exposure did not differ between healthy subjects receiving 40 mg and subjects with T2DM receiving 40 mg.If you have Type 2 diabetes, checking your blood sugar levels regularly can help you detect and address hypoglycemia quickly.GLP-1RA was initially approved for the treatment of type 2 diabetes, surprisingly exhibiting a distinct weight loss effect while controlling blood glucose (Monami et al., 2012; Xu et al., 2020).The global oral semaglutide phase III program, PIONEER, consists of 12 phase III clinical studies and has enrolled a total of 9542 subjects with T2DM as of 2020. MedicineNet does not provide medical advice, diagnosis or treatment. The drug interactions listed above are not all of the possible interactions or adverse effects. Never begin taking, suddenly discontinue, or change the dosage of any medication without your doctor’s recommendation. Once weekly SC dose escalation schedule Switching between Ozempic (SC) and Rybelsus (oral) The course of treatment was 68 weeks for Wilding, Rubino and Wadden et al., but only 52 weeks for O’Neil et al.’s study. O’Neil et al., used a smaller dose of semaglutide that was given once daily at 0.05 mg to 0.4 mg. All were adults ≥18 years old with a BMI of ≥30 kg/m2 or ≥27 kg/m2 with at least 1 treated or untreated weight-related comorbidity without diabetes. (B) Sensitivity analysis showing the effect of semaglutide on mean weight difference versus placebo. (A) Forest plot showing the effect of semaglutide on mean weight difference versus placebo. There was an 11.85% mean difference for weight reduction between the treatment groups, favoring semaglutide (mean difference -11.85, 95%CI -12.81,-10.90, p2 43%) (Figure 3A). All trials were double blinded, randomized, using interactive web-based response system with identically looking placebo and semaglutide. As for other bias, it was also deemed questionable since all trials had confounding factors such as diet and exercise adherence that may have significantly affected the magnitude of weight loss. For the SUSTAIN trials shown, estimated mean changes from baseline in body weight included only data obtained before initiation of any rescue medication or before premature treatment discontinuation. The PIONEER 5 trial was conducted to explore the efficacy and safety of oral semaglutide 14 mg vs. placebo in patients with T2D (most commonly at an advanced stage) and moderate renal impairment (estimated glomerular filtration rate of 30–59 mL/min per 1.73 m²) (31). Once-daily doses of oral semaglutide (14 mg only or 3 mg, 7 mg, and 14 mg) were assessed in most trials in the PIONEER program (26–32); however, the 3 mg dose is not approved as a maintenance dose and data are not included here. This article describes results from global clinical trial programs that established the efficacy of subcutaneous and oral semaglutide in a range of clinical settings and discusses factors that may influence the choice of formulation in individual patients. Others stopped early because of side effects or because the scale did not move as they hoped. Combining an oral approach with structured lifestyle supports and monitoring improves the chance of a good outcome. The best choice depends on your goals tolerance to side effects cost coverage and what you are willing to accept in terms of average results. People who combine the medication with sensible changes to eating, activity, sleep, and stress management tend to see better outcomes. The right path depends on medical suitability, personal preference, cost, and what you want from treatment. Oral semaglutide should be taken on an empty stomach and swallowed whole with up to 120 mL of water. Liraglutide with or without SGLT2i background medication, as were the occurrence of gastrointestinal AEs . In general, there were no statistically significant treatment interactions found between treatment and subgroups . The potential impact of background therapy in the PIONEER trials is an important consideration.