FDA approved exenatide (Byetta) as the first GLP-1-RA for the treatment of T2DM . Clinical research on GLP-1-RAs began in earnest in the early 1990s, with researchers exploring their potential for glucose regulation and weight management . Subsequent research has led to the development of long-acting GLP-1-RAs that can be administered weekly, further improving patient convenience and potentially enhancing treatment adherence . Rapid weight loss from GLP-1 agonists promotes fat burning throughout the body, including delicate facial areas. This helps explain why changes appear more pronounced and “deflated” compared to slower weight loss. This phenomenon isn’t unique to these medications—any method causing quick fat reduction (bariatric surgery, extreme calorie restriction) can produce similar effects. If you have a significant amount of weight to lose or very high blood sugar levels, the changes might seem more dramatic and potentially quicker as your body moves towards a healthier range. The answer varies depending on each individual's health goals, how they respond to the medication, and their ability to maintain lifestyle changes. A common question regarding GLP-1 agonist therapy is whether it needs to be a lifelong treatment. Clinical guidelines also stress the importance of healthcare providers being well-versed in the proper use, action, and dosing of GLP-1 agonists, as well as actively managing any complications that may arise. This strategy involves starting with a lower dose and slowly increasing it, allowing patients to acclimate more easily and reducing the likelihood of gastrointestinal discomfort. ⚠️ When to Seek Emergency Care Dual agonists such as tirzepatide (GLP-1/GIP) have demonstrated superior weight loss and glycemic control compared to GLP-1 RAs alone,104 likely due to complementary mechanisms involving both incretin pathways. While current studies have demonstrated substantial short-term weight loss and metabolic improvements, the sustainability of these outcomes over extended periods requires further exploration. The long-term effects of GLP-1 RA use for weight loss remains an important area for future research. Recognizing obesity as a chronic disorder underscores the need for long-term pharmacological treatment, similar to the approach used for managing type 2 diabetes or hypertension to achieve optimal control.9 A total of 350 patients were randomly assigned to either receive Lixisenatide or a placebo. The last study in the GetGoals series, initiated in 2013, examined the efficacy and safety of Lixisenatide in individuals aged 70 years or older with T2DM that was uncontrolled with their current antidiabetic treatment. Building on the findings of GetGoal-Duo 1, the GetGoal-Duo2 trial compared Lixisenatide against a once- or three-times-daily mealtime insulin in patients on titrated basal insulin. It was conducted at a single obesity centre that receives regional referrals, and some data from the cohort were missing. Being retrospective in nature, these data reflect real-world obesity management practices to a greater extent than RCTs. Controlling for drug concentrations reduces but does not completely eliminate this association, suggesting additional mechanisms.28 These have not yet been elucidated but may be due to sex-related physiological differences in obesity and hormonal appetite regulation, including leptin, ghrelin and insulin signalling.21 This is thought to be partially due to a lower average body mass, resulting in higher drug concentrations at any given fixed dose. The average baseline BMI of patients in this cohort was 43.5 kg/m2, and the average age was 47.2 years. We also discuss total cost and cost-effectiveness compared to other categories, long-term adherence, barriers to use, and reasons for discontinuation of this drug category. “Happy that there is a place affordable so I can take care of me by losing weight. I’ve tried other telehealth companies and by far this is the best one! I’m down 19# in 3 weeks. Recently, a daily oral semaglutide formulation that showed clinical efficacy comparable to the once-weekly subcutaneous preparation was approved 61,62. Currently, there are GLP-1 RAs that are injected once daily (Lixisenatide and liraglutide), twice daily (exenatide bid), or once weekly (dulaglutide, albiglutide, and semaglutide). While GLP-1 RA-induced deceleration of gastric emptying and occasional nausea may contribute to the weight-reducing effects, they appear to play a minor and temporary role . This approach furnished several clinically useful orally bioavailable small-molecule drugs in the drug market, such as sitagliptin, saxagliptin, linagliptin, and vildagliptin. Patients with T2D who require better glycemic control, want to lose weight, and are not interested in injectable medication may find oral semaglutide to be an appealing alternative . Safety comparison Finally, the microbiome has a variety of mechanisms through which it affects obesity, and pre/probiotic therapies could be a helpful addition to a weight loss regimen 58,59.EQW treatment also led to sustained weight loss, improved glycemic control, and a decreased risk of hypoglycemia after 84 weeks .SURMOUNT-1, the most comprehensive study on patients with obesity and diabetes, included 2539 adults with an average body weight of 104.8 kg and an average BMI of 38.0.Despite these challenges, when GLP‐1RAs are used effectively and consistently, they show substantial benefits in weight loss, most so the newest medications semaglutide and tirzepatide.To assess methodological quality and internal validity, we applied the Cochrane Risk of Bias 2.0 (RoB 2) tool for randomized controlled trials .Several studies have demonstrated at least equal performance with a low-carbohydrate compared to a high-carbohydrate diet if people are allowed to adapt for at least 4-weeks 84, 251.These medications work by mimicking a hormone naturally produced in your gut that helps regulate blood sugar and appetite.Currently, there have been eight completed studies related to tirzepatide, a new agonist of GIP and GLP-1 receptors."Ozempic butt" describes loose or sagging skin on the buttocks after losing substantial weight quickly. The 2022 WTW Rx Collaborative Annual Report found that, across all Collaborative employers, two of the top four drugs by spending were GLP-1’s used for diabetes. GLP-1 drugs provide benefits beyond lowering A1C, a common measure of diabetes management. The manufacturer is also studying semaglutide for Alzheimer’s disease and non-alcoholic steatohepatitis (NASH or fatty liver disease). There are clinical and financial impacts from obesity that may be mitigated by preventive measures as well as medication. Karagiannis et al. found that tezepatide had a significant dose-dependent advantage in weight loss compared with placebo, GLP-1R agonists, and basal insulin (130). EX long-acting preparation can reduce weight, but there are few related clinical studies, and most focus on patients with T2DM. In patients with T2DM who are poorly controlled by metformin, increasing DUL from 1.5mg to 3.0mg or 4.5mg can provide glycosylated hemoglobin and weight loss related to clinically relevant doses and has similar safety (111). At 26 weeks after treatment, the weight loss was -2.29 ± 0.24 kg for 1.5 mg DUL, -1.36 ± 0.24 kg for 0.75 mg DUL, and -2.22 ± 0.24 kg for metformin (110). Compared to general practice, the more frequent and structured use of RDNs and MNT in these trials could be one reason why these trials demonstrated larger weight reductions than seen in real-world GLP-1 utilization for obesity. Robust social networks improve health outcomes by reducing stress, increasing motivation, and encouraging accountability.198,199 Given the network effects of obesity and the added mortality impact of social isolation/loneliness among individuals with obesity, new interventions should be studied to promote social connectivity in conjunction with GLP-1 use.200,201 Clinicians can support individuals by conducting GMV or shared medical appointments (see below), recommending in-person or virtual participation in weight management groups or peer support groups, and addressing barriers to social engagement, such as isolation or mobility challenges.202,203 Substance use and cessation have complex associations with obesity, with overlapping brain pathways with food reward and disordered eating.187,195 Through these interrelated pathways, GLP-1s use may also help reduce alcohol and other substance use disorders.196 In a recent phase 2 randomized trial, 9 weeks of low-dose semaglutide in 48 outpatient participants with alcohol use disorder led to reductions in some but not all measures of alcohol use and craving. There has also been plenty of media buzz about anecdotal side effects with names like “Ozempic face” and “Ozempic butt.” A small number of users may experience gastrointestinal effects so severe that they need to stop taking the medication. Additionally, a minority of users will find it necessary to discontinue the drug because they cannot tolerate the side effects. Once you’ve received your prescription, you can reach out to your health coach at any time via the mobile app. Nurx provides progress tracking and healthy diet and exercise recommendations on their app. Nurx providers have expertise in women’s health, and the majority of the medical team is made up of women. According to the Centers for Disease Control and Prevention (CDC), the prevalence of obesity in the U.S. has grown from 30.5% over 1999–2000 to 41.9% over 2017–2020. Anton Pottegård reports participation in research projects funded by Alcon, Almirall, Astellas, AstraZeneca, Boehringer‐Ingelheim, Novo Nordisk, Servier and LEO Pharma(all regulator‐mandated phase IV‐studies), and an unrestricted research grant from Novo Nordisk, all with funds paid to the institution where he was employed (no personal fees) and with no relation to the work reported in this article. Adverse events in the obesity population and, in particular, long‐term safety outcomes remain insufficiently studied. Adverse events, particularly gastrointestinal disturbances, frequently lead to discontinuation, but otherwise, real‐world data provide little evidence for severe adverse effects. Numerous practice guidelines recommend multicomponent, evidence-based nutritional and behavioral therapy for adults with obesity, but use of such therapies with GLP-1s is not widespread. An expert group comprising multiple clinical and research disciplines appraised the scientific literature, informed by expert knowledge and clinical experience, to identify and summarize relevant topics, priorities, and emerging directions. Nevertheless, factors such as older age and severity of disease may influence the selection of appropriate candidates for these therapies due to risk of sarcopenia. There are several potential reasons underlying this heterogeneity, including population, drug-specific/molecular, and comorbidity effects. GLP-1 RAs: general effects and comparisons Although a leave-one-out sensitivity analysis (Supplementary Fig. S1) showed that excluding this study did not alter the overall results, our findings should be interpreted with caution when applied to this specific population. Only two of the included trials were conducted in Asian populations; the others included participants from diverse racial. Fourth, our subgroup analysis found that studies conducted in North America reported greater efficacy. Despite the limited number of studies, a consistent trend was observed. The GLP-1 related medications are particularly costly. Additionally, drugs targeting hunger or satiety signaling have been actively studied and have shown increased adoption by physicians. Patients who are less comfortable with injections may be good candidates for oral medications. Some medications are administered orally, and others are given as subcutaneous injections. Future studies will investigate the effect of MariTide on cardiovascular disease, heart failure, chronic kidney disease, and obstructive sleep apnea. It is therefore the synergistic actions of GLP-1 in the gut and brain, acting on both central and peripheral receptors that seem responsible for the effects of the hormone on satiety (Fig. 1). Mirroring these findings are neuroimaging studies showing that peripherally administered GLP-1 affects brain activity in areas involved in the regulation of feeding 22, 23. Also, knock down of the preproglucagon gene in the NTS has been shown to result in hyperphagia and weight gain . It is important to note that GLP-1-RAs are not suitable for all types of obesity. This combination is particularly advantageous for individuals who are overweight or obese, especially those with significant excess weight. The first GLP-1-RA, exenatide, was approved by the FDA in 2005 for the treatment of T2DM . In this context, glucagon-like peptide-1 receptor agonists (GLP-1-RAs) have emerged as a promising class of medications. Moreover, long-term adherence to lifestyle changes remains a significant challenge, with many individuals regaining lost weight within 1-5 years . Before FDA approval specifically for obesity, off-label prescription for weight loss created GLP-1 shortages for patients with diabetes. Results from drug trials support claims that GLP-1s are different than other weight loss medications, not only in terms of mechanism of action but also health benefits. The logical, but yet to be tested, expectation is that HWC as an adjuvant intervention to GLP-1 prescription will improve medication adherence and encourage sustained weight loss and health benefits in patients with obesity. A major issue with GLP-1RAs is that many patients stop using them within the first year due to side effects or high costs of the medications, especially if not covered by insurance. GLP-1RAs, like liraglutide, semaglutide, and tirzepatide, help manage weight by mimicking hormones that control blood sugar and appetite. Real-world studies demonstrate high discontinuation rates of GLP-1RAs (20%-50%) within the first year, and the use of much lower doses than those evaluated in clinical trials. GLP-1-RAs have been shown to benefit cardiovascular risk factors in addition to their primary functions of reducing glucose levels and facilitating weight loss. A previous study has shown significant decreases in body weight, ranging from 5% to 15% of the initial body weight . An illustrative instance is the SUSTAIN-7 study, which revealed that semaglutide yielded significantly more significant reductions in HbA1c levels than dulaglutide (-1.8% vs. -1.4% for the highest doses) . Comparative tests have demonstrated that newer GLP-1-RAs, including semaglutide, offer superior glycemic control compared with previous medications. Fibre and Gut Health Synergy If symptoms persist beyond 2-3 weeks or are severe, contact your provider — dose adjustment may help. Hair typically regrows within 6-12 months as your weight stabilizes. Practical guidance for daily life while taking GLP-1 medications. Your provider will review your medical and family history for thyroid conditions before prescribing GLP-1 medications. No — GLP-1 medications are not habit-forming or addictive. Effects of GLP-1RAs on atherosclerosis and atherosclerosis in the setting of diabetes This study developed pharmacodynamic models for 12 GLP-1RA drugs and conducted quantitative analyses of their time-course relationships, dose-response relationships, factors influencing efficacy, dropout rates, and adverse events. First, some GLP-1RA drugs are still under development, and the related clinical trial data are limited, which may affect the robustness of the pharmacodynamic models. Additionally, large-scale real-world studies indicate that GLP-1 class drugs may cause severe adverse reactions, such as acute pancreatitis, cholelithiasis, and acute kidney injury , , , . Therefore, the final approved dosages or titration schedules for these medications may be subject to changes, which requires a cautious interpretation of the current findings. Second, the data used in this study were derived from literature summaries rather than individual patient data, limiting our ability to access complete patient information and thus affecting the accuracy of our analysis of the factors influencing efficacy. This is particularly true for drugs with few reported efficacy data points, making it challenging to accurately estimate their ET50 values. Particularly, the safety profiles of GLP-1RA drugs that are still under development require further investigation with larger samples. Thus, dropout rates can reflect the safety and efficacy of medications to some extent. The AWARD-6 showed no difference in reported GI AEs between dulaglutide and liraglutide.20 The frequency of nausea in both groups peaked at week one and gradually declined thereafter. GI symptoms once again were most prominent and similar across the two groups, although the liraglutide group reported loss of appetite at a higher rate (6.4% versus 2.5%) and showed higher increases in lipase (8.4% versus 2.5%). The mechanism for the GLP-1 RAs increasing URIs and nasopharyngitis cases has not been elucidated, but the consistency across trials suggests that these are still important considerations with this class. It was also reported in the AWARD-1 trial, where rates were consistent across groups, including placebo (4% dulaglutide 1.5 mg, 5% dulaglutide 0.75 mg, 4% exenatide and 4% placebo). Overall, preceding or combining GLP-1s with intensive behavioral therapy shows promise in increasing achieved weight reduction. While the specific nutritional and other behaviors contributing to weight maintenance post-GLP-1 therapy have not been rigorously studied, other observational data elucidate general predictors of successful long-term weight reduction. Just as occurs following GLP-1 discontinuation, weight regain is common with waning adherence to dietary and physical activity weight loss interventions. Standardized clinical workflows that incorporate structured programs of stepped therapy, supported by nutritional and lifestyle interventions, could also help promote more effective and cost-effective use for individuals and healthcare systems. Nearly 1 in 3 prescribed medications are never filled, and individuals regularly adhere to only half of prescribed agents.276 Evidence-based strategies to improve general medication adherence include dose simplification, patient education, electronic reminders, reduced out-of-pocket costs, and patient incentives.5,276 Integrating GLP-1 use with longitudinal, structured nutrition and lifestyle programming might also support simplified dose titration schedules and management of side effects. Liraglutide was the first GLP-1 approved for weight loss and was studied in the Satiety and Clinical Adiposity-Liraglutide Evidence (SCALE) trials.9 The initial SCALE study evaluated the efficacy of liraglutide 3mg once daily in individuals with BMI greater than 27kg/m2 with one or more comorbid conditions or BMI greater than 30kg/m2. Paloma Health can support you in achieving your weight loss goals by offering personalized treatment plans that integrate GLP-1s and other weight loss drugs and strategies designed to meet your unique health needs. Additionally, weight loss from GLP-1 drugs typically levels off after about 68 to 72 weeks, likely due to the body’s natural resistance to further weight loss. Focus on health improvements beyond the scale. Photos show dramatic changes in body shape. Wegovy targets weight management specifically. Data draws from head-to-head and pivotal trials. Talk with your healthcare team before starting or changing your exercise program to make sure the activities are safe for you. These steps make it more likely that blood sugar will stay in a healthy range. Living with type 2 diabetes involves learning about the condition and lifestyle changes. This helps to make sure there's enough supply of the drug for people who are stable on the medication for treating their diabetes, and it also helps employers manage their costs. For employers who will cover the drugs, there are strategies to manage costs. New and more effective GLP-1 drugs are expected to be approved soon. The function of GLP-1-RAs in treatment algorithms is expected to change and expand as more long-term evidence is collected and new medications are launched 96,97. Furthermore, GLP-1-RAs should be administered to patients with established adult-onset chronic CVD, because these drugs have been found to have cardiovascular benefits. The ADA recommends that patients with T2DM, particularly those with established ASCVD or a high cardiovascular risk, utilize GLP-1-RAs as the first-line therapy in conjunction with metformin. If you are a Mayo Clinic patient, we will only use your protected health information as outlined in our Notice of Privacy Practices. Sign up for free and stay up to date on research advancements, health tips, current health topics, and expertise on managing health. Rarely, SGLT-2 may be linked to a higher risk of infection in the feet and lower legs. These medicines work in the kidneys where they help take extra sugar out of the blood that then goes out of the body in urine. This study demonstrated that age significantly influences the weight-reduction effects of GLP-1RA drugs, with older individuals experiencing less weight reduction. The duration of the clinical trials included in this study ranged from 6 to 104 weeks, with a median treatment duration of 26 weeks. This study simulated the weight reduction effects of the drugs across three age groups (45, 55, and 60 years). This study compared the efficacy and safety profiles of different GLP-1 receptor agonists (GLP-1RAs) for weight reduction and explored the related influencing factors, providing quantitative information for the development of GLP-1RAs and their clinical use. The aim was to evaluate the sustained efficacy and safety of GLP-1 receptor agonists in the long-term management of obesity. This study was conducted as a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines to ensure methodological transparency and replicability . Additionally, as newer agents like tirzepatide enter clinical practice, evaluating their comparative durability becomes increasingly relevant. Pharmacological interventions have become a crucial component in the management of obesity, especially for individuals who do not respond adequately to lifestyle changes alone . Weight management medications don’t replace physical activity and healthy eating habits. Studies show that weight management medications work best when combined with a lifestyle program. Medications don’t replace physical activity or healthy eating habits as a way to lose weight. If you are overweight or have obesity, you might be able to lose weight with a lifestyle program that changes your behaviors and improves your eating and physical activity habits. Health care professionals use BMI to help decide whether you might benefit from weight management medications. BMI, body mass index; GLP-1, glucagon-like peptide 1; HbA1c, hemoglobin A1c; HDL, high-density lipoprotein; LDL, low-density lipoprotein. The most commonly dispensed GLP-1 agonists were liraglutide (52%) and dulaglutide (40%). The mean age in the final cohort was 48 years and mean body mass index was 37 kg/m2. This benefit surpasses its category, as seen in the SUSTAIN-8 research, where semaglutide significantly reduced HbA1c levels and weight loss more than canagliflozin, an SGLT2 inhibitor . It has shown superior glycemic control and weight reduction efficacy compared with other GLP-1-RAs. GLP-1-RAs differ from sulfonylureas and insulin because they may aid in weight loss and have a low risk of hypoglycemia . There were missing data on baseline BMI (3.1%), sex (2%), maximum semaglutide dose used (1%) and 25% of patients had missing weight measurements in the follow-up period. At SheMed, we know many of our patients make incredible progress but eventually hit a "plateau"—that frustrating point where weight loss slows down or stops. At SheMed, we know that many of our patients make incredible progress but eventually hit a "plateau" - that frustrating point where weight loss slows down or stops. Although the prevalence decreases temporarily in those aged 10–19 years, there have been consistent increases in the prevalence of overweight and obesity in the WHO European Region, and no Member State is on track to reach the target of halting the rise in obesity by 2025.It is possible to reduce the risks by eating enough protein and engaging in strength-building exercises, such as weight lifting.Those who complained of gastrointestinal adverse effects were also more likely to discontinue use as well as those who lost more weight.The study found that liraglutide 3.0 mg may provide health benefits for people with prediabetes and obesity.The results of multiple recent meta-analyses indicate that low-carbohydrate dietary patterns do at least as well, and often better, at promoting weight loss and certain risk markers for cardiovascular disease when compared with low-fat dietary patterns 40, 41, 178–180.This comprehensive literature review examines available research on these medications, focusing on their mechanisms of action, clinical effectiveness, safety profiles, and socioeconomic implications. We calculate your BMI based on your height and weight. It’s a hormone your body naturally makes to help control blood sugar, insulin, and digestion. When you need to lose weight and feel like nothing’s working, it’s easy to become despondent, but you’re far from alone. As the scientific community delves into these emerging areas, collaboration between researchers, healthcare practitioners, and policymakers is crucial to translate findings into accessible and effective interventions that promote individual and global well-being. Whether these conditions demonstrate the same robust therapeutic effects remains to be seen, but we believe these investigations hold the potential to uncover additional beneficial metabolic and physiological effects that broaden our understanding of therapeutic nutrition. 3. Long-acting GLP−1 receptor agonists: Once-weekly GLP-1 weight loss therapy isn’t just the latest trend—it represents a paradigm shift in how we approach metabolism, aging, and long-term health. For affluent patients who view health as a long-term investment, GLP-1 therapy is increasingly seen as more than a weight-loss shortcut. These medications not only help regulate blood sugar but also reduce appetite, slow stomach emptying, and promote a feeling of fullness, leading to meaningful and sustained weight loss. GLP-1 receptor agonists—originally developed to treat type 2 diabetes—are now making headlines as powerful, medically-supervised weight loss tools. Choosing a medication to treat overweight or obesity is a decision between you and your health care professional. In the past, some weight management medications were linked to serious health problems, and they were removed from U.S. markets. Losing weight also can improve some other health problems related to overweight and obesity, such as joint pain and sleep apnea. Weight loss of 5% to 10% of your starting body weight may help improve your health by lowering blood sugar, blood pressure, and triglyceride levels. Ask your health care professional about lifestyle treatment programs for weight management that will work for you. While low-carbohydrate diets have a strong track record in promoting equal or superior weight and fat loss than low-fat diets, there are fewer studies addressing combined low-carbohydrate intake with endurance training. We briefly discuss the literature on both endurance/aerobic and resistance/strength training and focus on studies that compared background diets that emphasized low-fat/high-carbohydrate versus low-carbohydrate/high-fat. Ironically, the “compensatory” responses to exercise that contribute to minimal weight loss appear to be more robust in people with greater adiposity , making weight loss even more challenging. This is consistent with evidence supporting a restraint on human metabolic rate in individuals who are extremely active and larger studies that show only about a quarter of participants exercising at a high dose do not compensate (i.e., they lose weight in response to exercise) . Productivity is reduced by high caregiver load, low quality of life, and early death due to obesity and T2DM. Improved GLP-1-RAs administration may help control obesity and T2DM, thereby lowering societal expenses . These effects mitigate the long-term consequences of chronic disorders 122,123. GLP-1-RAs have long-term economic implications, beyond drug expenses and healthcare savings. As GLP-1-RAs use increases, clinicians may need extra training to initiate and maintain treatment. GLP-1s reduce energy intake by 16-9% compared with placebo, related to changes in cravings, hunger, and fullness.56,147,148 Multiple studies demonstrate beneficial effects on food cravings and disordered eating. The approach to initiating pharmacologic therapy for obesity should be individualized, with a focus on overall physical health, mental health, and well-being rather than body weight alone. Side effects tend to decrease in frequency and severity with continuation of a stable dose.40 GI side effects are most frequent and include nausea (25-44%), diarrhea (19-30%), vomiting (8-24%), constipation (17-24%), and abdominal pain (9-20%).41-46 Although certain side effects have been reported more commonly with semaglutide than with tirzepatide, trial data suggest that such differences may be a reflection of variation in background (i.e., placebo group) rates in the enrolled trial populations, with the proportional increase in many side effects when compared to placebo being similar for the 2 agents (Table 2). In multivariate analyses, factors predicting larger responses with tirzepatide include female sex (2.4 higher odds of achieving a 20% weight reduction), lower baseline hemoglobin A1c (1.62 higher odds), no diagnosed hypertension (1.35 higher odds), and lower ALT (1.17 higher odds)21; and in univariate (crude) analyses with semaglutide, female sex (48% greater weight loss in kilograms), younger age (24% greater for age 2).16 These medications are approved by the Food and Drug Administration (FDA) for the treatment of obesity or overweight with weight-related comorbidities. These results reflect findings from large, randomized, placebo-controlled trials and represent one of the most meaningful advances in obesity treatment in decades. Importantly, current guidelines prioritize the use of GLP-1 RAs with demonstrated CV benefit (dulaglutide, liraglutide, and injectable semaglutide) in patients with atherosclerotic CV disease (ASCVD) and ASCVD risk, independent of baseline A1C. The risk of hypoglycemia is low with GLP-1 RAs and rates were similar across all GLP-1 RA treatment groups in the head-to-head clinical studies; although the risk was increased with concomitant SU therapy. In the PIONEER-4 trial, at 52 weeks, there was no difference in treatment satisfaction between liraglutide and oral semaglutide in regards to their DTSQ scores.24 The PIONEER-9 trial utilized the Diabetes Therapy-Related QOL (DTR-QOL) questionnaire to assess patient satisfaction. He promotes wellness through lifestyle changes, emphasizing exercise, healthy eating, and supportive relationships in addition to traditional metric goals. ABOM, is a board-certified family medicine and obesity medicine physician currently at Norman Regionals Primary Care South OKC clinic. The OMA has published a position statement on the use of compounded medications. Patients and doctors should always discuss the potential risks and potential benefits as they relate to that patient’s unique situation. In the spring of 2025, both tirzepatide and semaglutide came off the drug shortage list ending the legitimate use of compounded agents in the absence of specific exceptions. Here, we’ll explore the basics of GLP-1, how it works, and what current research suggests about its effects on fertility. While they work wonders for metabolic health, there’s a growing curiosity about how they might influence fertility and reproductive health. Researchers found that four in 10 patients (40.7%) were persistent with their medication one year after their initial prescription’s fill. These habits amplify the drug’s effects.However, given the safety or effectiveness concerns of anti-obesity drugs, many of the currently used drugs have limited clinical use.The interindividual variability in antiobesity efficacy is one of the most important challenges, because there are currently almost no reliable predictive models to assess the weight reducing potential at the individual level.The recent SUSTAIN (Semaglutide Unabated Sustainability in Treatment of Type 2 Diabetes), clinical trial program investigated the safety and efficacy of subcutaneous semaglutide, which has a 94% homology with endogenous GLP-1.10 The addition of a fatty diacid chain at position 26 improves albumin binding.The high price of GLP-1s has created a market for less-expensive compounded versions of the drugs.In the end, a personalized approach is key to optimizing both your metabolic and reproductive health.A study from FAIR Health published in May 2025 reports that more than 2% of U.S. adults took a GLP-1 for weight loss in 2024. These medications mimic a gut hormone to curb appetite and regulate blood sugar. Despite their increasing use, patient perspectives of these treatments remain underexplored. You should always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition or your specific situation. Any action taken as a direct or indirect result of the information in this article is entirely at your own risk and is your sole responsibility. Nausea, vomiting, diarrhea, and constipation — most common during the first few weeks and typically improve with time. Results vary by medication, dose, adherence, and baseline metabolic health. Eligibility depends on BMI, health history, and clinician evaluation. Medically reviewed answers from obesity medicine-focused providers. The drugs are expensive, and experts say the recent spike in popularity has already led to shortages and increased hesitancy among insurance providers to cover these drugs. You can also use Lark for reminders to take your medications and to record each dose when you take it.AWARD-6 is a randomized, open, parallel-grouped, multicenter, phase 3, non-inferiority study comparing the safety and efficacy of weekly DUL and daily LIR in patients with uncontrolled T2DM treated with metformin.For example, dietary changes or specific probiotics could potentially be used to cultivate a microbiome that is more responsive to GLP-1RA therapy, thereby optimising weight loss outcomes.Individuals should be assessed for risk of sarcopenia and osteopenia, seen in individuals who are older, sedentary, chronically ill, malnourished, or with type 2 diabetes.Real-world persistence and adherence to glucagon-like peptide-1 receptor agonists among obese commercially insured adults without diabetes.We anticipate that this review will generate data that will help biomedical researchers or clinical workers develop obesity treatments based on GLP-1R agonists.Also, knock down of the preproglucagon gene in the NTS has been shown to result in hyperphagia and weight gain . Weight loss achieved with standard doses of GLP-1 agonists (GLP-1a) among real-world patients with type 2 diabetes has not been determined. It is established that people with diabetes have more difficulty losing weight than individuals without diabetes and differences between individuals with and without diabetes were consistently confirmed also for GLP-1RAs. The rates of these adverse events across SCALE and STEP trials were comparable between GLP-1 RAs and placebo. The table below includes limited information about weight-loss medications. These medications have side effects, some of which could be severe. Although some health care professionals prescribe them for longer periods, not many research studies have looked at how safe and effective they are for long-term use. The table below lists prescription drugs approved by the FDA for chronic weight management. “In my experience, people who use GLP-1s for only a small amount of weight loss generally have worse side effects, especially vomiting and dehydration,” says Dr. Brown. While these types of meds can be used for smaller amounts of weight loss, Dr. Brown cautions against side effects of Ozempic and other GLP-1s. Other weight-loss drugs like Wegovy and Ozempic (semaglutide) and Mounjaro (tirzepatide) are also popular options. With the rapid shift in treatment patterns, there is a need for continuously updated population‐based drug utilization data, including key aspects such as costs and treatment persistence. Here, we summarise 10 selected areas that we consider of particular importance for further studies. Of note, the EMA has not included this in the European licensing of these drugs. Severe gastrointestinal symptoms, including gastroparesis and intestinal obstruction/ileus, have been anecdotally reported with GLP‐1RA use, with a pharmacovigilance signal for intestinal obstruction seen in WHO's VigiBase.90 These signals have not generally been observed in RCTs74 and there is currently sparse real‐world evidence existing from large epidemiological studies. Www.fda.gov/drugs/drug-safety-and-availability/fda-approves-first-treatment-weight-management-people-certain-rare-genetic-conditions FDA approves treatment for chronic weight management in pediatric patients aged 12 years and older. Www.fda.gov/drugs/drug-safety-and-availability/fda-approves-weight-management-drug-patients-aged-12-and-older GLP-1 agonists, used to treat type 2 diabetes, have been shown to be effective in promoting weight loss in preclinical and clinical studies. Whether it is a significant reduction in body weight or improved metabolic health, the testimonials illustrate a compelling narrative that supports the integration of GLP-1 treatments into modern weight management strategies. One groundbreaking study highlighted that patients receiving GLP-1 receptor agonists not only experienced considerable weight loss but also improved glycemic control, which is pivotal in diabetes management. The real magic, especially for significant weight loss or improved A1C levels, takes a bit more time to manifest fully. For many people, the initial effects of medications like Ozempic, Wegovy, or Mounjaro aren’t a dramatic overnight transformation. He specializes in evidence-based health information, medications, and chronic health topics. Wegovy treats chronic weight management in adults with obesity or overweight plus related conditions. Benefits often outweigh risks for eligible patients. Regular exercise complements the action of GLP-1 receptor agonists by improving insulin sensitivity and aiding weight maintenance. This approach combines medication with lifestyle modifications and holistic health strategies. An integrative approach is essential to maximize the benefits of GLP-1 agonists while minimizing potential side effects. The GLP-1 medication needs to be part of a multifaceted and integrated approach to optimizing your metabolic and overall health. Some studies have investigated the use of GLP-1s in managing addictive behaviors, particularly disorders involving alcohol use. The economic impacts of the obesity epidemic are also important. Childhood and adolescent obesity have adverse psychosocial consequences; they affects school performance and quality of life, compounded by stigma, discrimination and bullying. In 2021, higher-than-optimal BMI caused an estimated 3.7 million deaths from noncommunicable diseases (NCDs) such as cardiovascular diseases, diabetes, cancers, neurological disorders, chronic respiratory diseases, and digestive disorders (3). In most cases obesity is a multifactorial disease due to environmental and psycho-social factors and genetic variants. While just 2% of children and adolescents aged 5–19 were living with obesity in 1990 (31 million young people), by 2022, 8% of children and adolescents were living with obesity (over 160 million young people). When blood sugar starts to rise after a person eats, these medicines cause the body to make more insulin.Tirzepatide has demonstrated greater efficacy compared to GLP-1 drugs in improving glycemic control and inducing weight loss.First, loss of lean mass in response to a ketogenic diet is often accompanied by an overall greater loss in body mass, such that body composition (i.e., percent body fat) improves 254, 255.We prioritized studies of GLP‐1RA‐based drug use in populations with obesity, but we also assessed prior systematic literature reviews and recent large studies of GLP‐1RA use in populations with T2D, as evidence for various outcomes is still scarce for populations with obesity.The vagus nerve plays an important role in mediating these effects as shown in both animal and human models, perhaps through its action on the circular muscle of the intestines 16, 42-44.The baseline characteristics of the study populations, study drugs and study designs may be considered as possible reasons for the variability 170.Rapid weight reduction from (but not limited to) GLP-1 use frequently leads to loss of both fat and muscle mass.62,63 In the STEP 1 trial, of the average 13.6-kg–weight reduction, 8.3 kg (62%) was fat mass and 5.3 kg (38%) was lean body mass (including muscle and other nonfat tissues).14 Because muscle mass is about half of lean body mass, this corresponds to ∼20% of total weight reduction being muscle loss.These services include virtual consultations, personalized treatment plans, medication delivery, and ongoing clinical support. If weight at the 12-month period was not available, the last recorded weight was carried forward (1% were missing a weight category). Multinomial regression models were constructed with the three percent TBWL categories and independent variables using forced entry modelling with age, sex, baseline BMI, type 2 diabetes mellitus (T2DM), depression, sedentariness, anxiety and depression as covariates. Baseline characteristics and independent variables were compared across TBWL categories using the Kruskal-Wallis equality-of-populations rank test (2 df) or one-way analysis of variance with Tukey’s honestly significant difference post hoc test. For the primary endpoint, baseline and follow-up weight were measured at the initial and subsequent physician visits using a platform bariatric weighing scale. The low-or very-low fat intake approach is recommended for inducing significant short-term weight loss, but its long-term efficacy is not superior to dietary interventions with higher fat content .This study compared the efficacy and safety profiles of different GLP-1 receptor agonists (GLP-1RAs) for weight reduction and explored the related influencing factors, providing quantitative information for the development of GLP-1RAs and their clinical use.Nurx provides progress tracking and healthy diet and exercise recommendations on their app.The STEP-1 trial is considered the pivotal trial that demonstrated 14.9% weight loss at 68 weeks with semaglutide 2.4 mg .In the past, some weight management medications were linked to serious health problems, and they were removed from U.S. markets.Clinical practice guideline for the evaluation and treatment of children and adolescents with obesity.Some studies suggest the delayed gastric emptying is only in the first hour and overall gastric emptying did not seem to be affected.7,8 GLP-1 is also expressed in the brainstem, endocrine pancreas, and immune system.Patients also get access to behavior-change lessons and a habit tracker to record medication, weight, sleep, movement, and nutrition. Established benefits beyond obesity Initially approved for T2DM, agents such as liraglutide and semaglutide have shown substantial efficacy in reducing body weight and improving cardiometabolic parameters even in non-diabetic populations 4,5. Due to the heterogeneity of weight loss with GLP-1 analogue therapy, practical and accessible predictors of response are needed to help guide the selection of patients who may benefit from these medications. Additionally, a small proportion of participants were taking liraglutide rather than semaglutide, potentially lowering the observed weight loss effect size. The lack of association of diabetes with weight loss response contrasts with existing randomised controlled trials (RCTs).27,29 This discrepancy may be mediated by differences in prescribing practices, adherence and tolerance that may not be accounted for by RCTs. The indication is to effectively reduce glycosylated hemoglobin levels in patients with T2DM by reducing fasting and postprandial blood glucose levels (61, 62). As a synthetic analog of its endogenous exendin-4, compared with exendin-4, LIXI deleted one proline and added six lysine residues, which increased its binding affinity with the GLP-1R by four times and increased its circulating half-life (58, 59). Lipotoxicity induced by saturated free fatty acids plays a vital role in renal injury in obese patients (49). Body weight was reduced by an average of 1.5 kg with exenatide compared to placebo . The DURATION-7 study aimed to investigate the efficacy and safety of adding once-weekly exenatide 2 mg or placebo to insulin glargine titration (IG) ± metformin in patients with T2DM who had inadequate glycemic control. After 26 weeks, the HbA1c (%) reductions with EQW were −1.53, −1.63, and −1.15, as compared to MET, IOP, and SITA, respectively. Similarly, patients who transitioned from pioglitazone to exenatide once weekly sustained improvements in HbA1c and fasting blood glucose, along with significant weight loss (−3.0 ± 0.3 kg). With that in mind, Dr. Gasoyan and colleagues looked at the proportion of patients who achieved 10% or more weight reduction. The proportion of patients who were persistent with semaglutide was 45.8% versus 35.6% in patients receiving liraglutide. Most of the patients received treatment for type 2 diabetes. Such comprehensive care will make clinicians more effective stewards of these medications and positive contributors to their patients’ health. The figure on the right illustrates the model-predicted typical values of weight reduction for Liraglutide (A) and Semaglutide (B) at various age levels. The box plot on the left displays the observed weight reduction values for Liraglutide (A) and Semaglutide (B) across different age groups. Points on the right indicate the typical values of the pure effect of 52-week weight reduction for each drug, with error bars denoting 95 % CIs of the estimates. Distribution of typical pure effect values for weight reduction at week 52 for each drug Clinical studies have demonstrated the efficacy of semaglutide in promoting significant weight loss in individuals with obesity. However, how these medications perform in real life can be different from the controlled settings of clinical trials, in which patients are carefully selected and their treatment plans closely followed. Evidence from observational studies within type 2 diabetes or obesity populations suggests frequent gastrointestinal disturbances in GLP-1RA users, as also observed in trials, but no clear increase in risks of severe events like pancreatitis or pancreatic cancer, thyroid disorders, or depression and self-harm. These drugs are more expensive than traditional diabetic treatments, which may be a barrier for patients and the healthcare system. The Obesity Society Guidelines recommend the use of GLP-1-RAs for weight loss, particularly in patients with obesity-related comorbidities. Furthermore, GLP-1-RAs are indicated as a first-line treatment for patients seeking to reduce weight gain or encourage weight reduction. To enhance the safety of GLP-1-RAs in clinical practice, it is critical to carefully select patients and adequately manage gastrointestinal side effects, despite the medications' typically excellent tolerance . One GLP-1RA, liraglutide, has been approved to treat obesity, and another, semaglutide, is in clinical trials.Participants who had weight data in the 72-week window were similar to those who did not (Table S4).Health consequences of excess weight include cardiovascular diseases, type 2 diabetes, dyslipidemia, and increased mortality.If weight at the 12-month period was not available, the last recorded weight was carried forward (1% were missing a weight category).Pharmacological interventions have become a crucial component in the management of obesity, especially for individuals who do not respond adequately to lifestyle changes alone .GLP-1 medications increase insulin release when blood sugar is high, helping cells better absorb glucose from the bloodstream.Although rates of adverse effects differ between specific agents, the most common adverse effects with the GLP-1 RA class are gastrointestinal (GI) related (nausea, vomiting, and diarrhea) and injection site reactions.Individuals prescribed Semaglutide injection for weight loss between January 2021 and January 2023, multi‐centred, Electronic Medical Records, US What strategies can be employed to preserve lean body mass and mitigate weight regain after treatment discontinuation? Recent insights into body composition changes, potential psychiatric effects, and perioperative risks highlight the importance of individualized care and ongoing monitoring. Research efforts should focus on understanding the variability in individual responses to GLP-1 RAs, developing predictive models, and integrating these insights into clinical practice.110 Personalized approaches could lead to more effective weight management, improved patient satisfaction, and better long-term health outcomes.111 In the tirzepatide versus placebo groups, diarrhea (12–21% vs. 10%) and nausea (13–18% vs. 3%) were the most frequent treatment-emergent side events (SURPASS-5) . The SURPASS-3 study, like the other studies previously mentioned, showed the same mild to moderate gastrointestinal adverse events, which decreased over time. Serious adverse events were reported in 5 to 7% of patients receiving tirzepatide and 3% of those receiving semaglutide . This table underscores that no single method guarantees permanent weight loss. Other weight loss approaches, such as gastric bypass or traditional dieting, also face this challenge. Similarly, the SURMOUNT-4 trial found that discontinuing tirzepatide led to a 14% weight regain after 52 weeks. A comprehensive review from Peking University analyzed 11 clinical trials involving 2,466 participants. The cost-effectiveness of GLP-1-RAs varies by agent and patient group, but their long-term benefits and potential to minimize diabetes-related healthcare expenditures make them an affordable diabetes treatment option . However, when considering these medications, it's crucial to assess their long-term effects on health outcomes and overall healthcare costs . In a German sickness fund study, the average annual treatment costs were €6,851 for GLP-1 receptor agonists, compared to €4,895 for empagliflozin (an SGLT2 inhibitor). GLP-1-RAs are becoming increasingly important in the treatment of cardiometabolic disorders, as shown by their inclusion in key recommendations for diabetes, CVD, and obesity management. How Can You Boost Your Body’s Natural GLP-1 with Everyday Foods? In the UK, these medications are available by prescription only for individuals with a BMI of 30 or above (or 27 or above with weight-related health conditions). GLP-1 (glucagon-like peptide-1) receptor agonists were originally developed for type 2 diabetes but have revolutionised obesity treatment. There is no clinical evidence that GLP-1 patches work for weight loss; however, research shows that GLP-1 weight-loss injections can support a weight loss of around 15-25% on average. Two trials have supported an increase in the risk of all types of thyroid carcinoma 200,201. All GLP-1 agents have carried an FDA black-boxed warning of increased risk of C cell thyroid carcinoma and recommended agents used in patients with a personal or family history of multiple endocrine neoplasia type 2A or 2B. Although both the association of retinopathy and NAION can be seen with GLP-1 use, it is worth noting that a majority of cases occurred in patients with type 2 diabetes. In the People interview, Williams shared that before taking a GLP-1, nothing was working for her weight loss. Your healthcare provider can help determine whether microdosing fits your health goals, such as weight management, insulin sensitivity improvement, or appetite regulation, and help adjust the dose accordingly. By comparing the efficacy and safety profiles of low-dose versus full-dose GLP-1 treatments, researchers can better tailor therapies to the needs of individual patients and improve treatment outcomes. However, animal studies suggest that low-dose GLP-1 activation can still help balance and manage blood glucose levels without triggering full-scale gastrointestinal side effects. There aren’t any significant published studies on human microdosing of GLP-1 drugs. Some people may need to lose weight more quickly, for example, those who need to qualify for surgery for a debilitating condition. Visits with primary care physicians and nonobesity medicine specialists who care for individuals with obesity are usually short and centered on acute illness or needs, screening discussions, and medication management.104 In addition, access is limited to lifestyle medicine approaches for obesity and its comorbidities. Grade I-A is an indicator of the recommendation and its level of evidence, here denoting that the procedure or treatment should be performed/administered and has strong evidence that it is useful/effective. The current US list price for GLP-1s for obesity ranges from ∼$12,000 to $16,000 per year.2 Full costs may be incurred by those who self-pay, due to either off-label use or no payer coverage. Less common side effects included dyspepsia, fatigue, headache, eructation (belching), hair loss, gastroesophageal reflux, dizziness, and gastritis (Table 2). Using functional magnetic resonance imaging (fMRI), they found that exenatide decreased food intake and food-related brain responses in T2DM patients and participants with obesity compared to placebo. Studies used GLP-1 analogues of any dosage and any duration among adults with obesity without diabetes or any other medical diseases, compared with a placebo or any other intervention. Everything you need to know about GLP-1 weight loss medications — eligibility, side effects, dosing, and what to expect. “Effectiveness of glucose-lowering medications on cardiovascular outcomes in patients with type 2 diabetes at moderate cardiovascular risk” was published in Nature Cardiovascular Research in April 2024. Recent FDA approvals have expanded indications for cardiovascular risk reduction, sleep apnea and chronic kidney disease. The anticipated price reductions from Medicare negotiations may influence employer-sponsored health plans to adjust their coverage policies for GLP-1s. Those who regained weight after discontinuation of GLP-1s were more likely to restart the medications. Those who complained of gastrointestinal adverse effects were also more likely to discontinue use as well as those who lost more weight. This could be because those with obesity had a more difficult time obtaining insurance benefits for these expensive medications. These medications have shown potential in reducing the occurrence of nonfatal myocardial infarctions, nonfatal strokes, and cardiovascular mortality. Multiple GLP-1-RAs agonists have shown significant cardiovascular benefits in extensive outcome trials, marking an essential advancement in T2DM management. Research has shown that the decrease in weight achieved using GLP-1-RAs may be maintained for extended durations, with some individuals continuing to lose weight even after the first year of medical use . Additionally, a few studies suggest a decrease in the intestinal absorption of glucose, which in turn aids glycemic management. A coach who understands the complexities of rapid weight loss, specifically with GLP-1, can help the patient persist with the treatment. They’ll also help manage side effects, make adjustments, and guide you toward your weight loss goals . If you meet the BMI criteria and are considering GLP-1 medications for weight loss, here’s how you can get started. GLP-1 medications are known to help with weight loss, but the results vary based on factors like your starting BMI, how well you stick to the medication plan, and changes in your lifestyle. This relationship can allow for dosage adjustments or alternative medications if one seems like a better fit for the patient. They are not regulated by the FDA and do not have proper studies to confirm their safety and effectiveness. These programs apply only to self-pay patientsand are not covered by insurance. However, both Eli Lilly and Novo Nordisk have direct purchase options that greatly reduce the monthly price for patients that do not have insurance coverage. Monitoring and managing side effects such as gastrointestinal difficulties and injection site responses may require additional outpatient visits and tests. Improved glucose control and fewer diabetes-related complications make this possible 106,107. These drugs may prevent cardiovascular events and save money while improving patient outcomes. Many patients search for visual charts to understand realistic outcomes. Focus on making healthy lifestyle choices and working with your healthcare team to find the best approach for you. GLP-1 medications can be a helpful tool for some, but they’re not the only solution. Ozempic is primarily approved for type 2 diabetes. So, if you have a diagnosis of type 2 diabetes and your doctor prescribes a GLP-1 medication to help manage your blood sugar, there’s a good chance Tricare will cover it. These conditions indicate the risk of developing terminal complications such as type 2 diabetes mellitus (T2DM), nonalcoholic steatohepatitis, and cardiovascular disease . The estimated prevalence of overweight was 31.1%, and obesity was 21.3%, with the highest prevalence being in the age range of 60–79 years, at 41.6% 5,6. Rates tend to be higher in higher-income countries, and the highest levels of overweight and obesity are found in Mediterranean and Eastern European countries. In the European Region, overweight and obesity have reached epidemic proportions, with higher prevalence levels among men (63%) than women (54%). To see the full potential of GLP-1 drugs in improving clinical outcomes, they should be accessible to members who need them most. Direct to consumer and direct to employer telemedicine providers can prescribe weight-loss drugs virtually. These factors have spurred the development of an entire industry focused on GLP-1-driven weight loss. Another significant observation was that liraglutide reduced blood pressure at all doses and reduced the prevalence of prediabetes (84–96% reduction) at 1.8–3.0 mg per day. Approximately 76% of people lost more than 5% of their weight with liraglutide 3.0 mg than with placebo (30%) or orlistat (44%). Those who received liraglutide lost significantly more weight than those who received a placebo or orlistat. Liraglutide was found to significantly reduce glycosylated hemoglobin compared to glargine and placebo and provided better glycemic control and weight outcomes . The LEAD-3 study investigated the safety and efficacy of liraglutide as monotherapy in 746 patients with early-stage T2DM.