The second study was a parallel design study by Tronieri et al 2020 that divided the intervention groups into three groups. Four studies out of eleven used Liraglutide,17,24–26 five out of eleven used GLP-1 infusion,16,20,27–29 and two out of eleven used Semaglutide.18,23 A total of 90 out of 220 participants were recruited in the GLP-1 analogues group in parallel group studies,17,23–25 and 182 participants were recruited in crossover design studies.16,18,20,26–29 So, the total of participants who used GLP-1 analogues were 272 participants. The term satiety, hunger, and fullness are the most assessed markers for appetite.31 Eleven out of twelve studies assessed the effect of GLP-1 analogues on appetite profile.16–18,20,23–29 All the studies used a 100-m VAS tool to assess the appetite. Evidence suggests substantial beneficial effects on weight and glycemic dysregulation. “There may be some direct benefits of the medication in the absence of significant weight loss, which is also why you should be talking to your doctor at length about why you’re using this medication.” The analysis from Dandelion Health, a health care analytics firm, is based on the electronic health records of nearly 17,000 people who were prescribed a GLP-1 from 2019 through 2023. People who met with their providers less frequently – and those living in underserved regions with broader health inequities – were more likely to discontinue GLP-1 treatment sooner. GLP-1 receptor agonists, such as semaglutide (Wegovy, Ozempic) and tripeptide (Zepbound), are medications designed to mimic the effects of natural GLP-1. Because patients often seek validation from physicians to lose weight, we can acknowledge their goal while emphasizing a more holistic approach to health, encouraging patients to engage in exercise they enjoy and eat nourishing foods that make them feel good and not deprived. Multiple glucagon-like peptide-1 (GLP-1) agonist medications, created for the treatment of type 2 diabetes mellitus, are now labeled for the treatment of obesity. The conclusion drawn from the study stated that irrespective of the type of surgery, liraglutide can treat the persistent or recurrent postbariatric surgery complication of T2DM by optimising glycaemic control along with a needful weight loss. In obese patients with nonalcoholic steatohepatitis (32% having diabetes), the LEAN trial using liraglutide or placebo in small group of patients showed more frequent resolution of NAFLD and less progression of fibrosis . There is a concern out there about muscle loss with these medications, and whether or not the loss of muscle, which always occurs with weight loss, is a little bit exaggerated with these medicines. So these medications can act as an adjunct to that and can help boost the weight loss for long term benefits. Now many people can achieve maybe 3 to 5% weight loss with lifestyle, but that’s pretty much where it goes. Matt EavesSo it sounds like based on what you just said, you’re not recommending this as a first line treatment for people who are wanting to lose weight. So the medications are for weight loss. This retrospective, propensity score–matched (PSM), cohort study was conducted using TriNetX (Cambridge, Massachusetts), a federated network of de-identified medical records from patients in 19 different countries. While other antidepressant classes (eg, tricyclic antidepressants) or other SSRIs (eg, paroxetine) may increase body weight, citalopram/escitalopram were chosen as they are common, first-line antidepressants that generally have little impact on body weight. Patients in the antidepressant cohorts experienced less weight loss compared with their respective matched cohorts not receiving antidepressants (citalopram/escitalopram −0.73 kg versus −1.74 kg; bupropion −0.84 kg versus −3.46 kg). After propensity score matching, the study found patients receiving citalopram/escitalopram were taking more antidiabetic therapies at baseline compared with patients not treated with an antidepressant. As a GLP-1/GIP/GCG tri-agonist, Retatrutide's interaction among the three receptors significantly enhanced its weight reduction effect. An analysis was conducted on the total dropout rates for the 12 types of GLP-1RA drugs. 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. Values exceeding 80 % suggest that the treatment duration has approached or reached its efficacy plateau. The results indicate significant variability in the efficacy of these drugs in reducing body weight. The incidence of nausea for most GLP-1RA drugs was significantly higher than that for placebo, particularly for Orforglipron and Exenatide, with relative risks (RR) of 10.1 and 7, respectively. Taking injectable Semaglutide (1.0 mg) as an example, the weight reduction effects at 52 weeks for subjects aged 45, 55, and 60 were 9.88 kg, 7.27 kg, and 6.24 kg, respectively, with the latter being 3.64 kg lower than the former (Fig. 6). The shaded gray area represents the range of treatment duration in the included studies, while the orange points indicate the effect values at 26 weeks and 52 weeks. This narrative review explores the metabolic effects of GLP-1 RAs in weight management, blood glucose, cardiovascular health, lipid profiles, and blood pressure. Additionally, we review the evidence of four recent clinical trials, two systematic reviews, and two meta-analyses describing the efficacy of GLP-1 agonists in decreasing weight, lowering HbA1c, and improving obesity comorbidities. In this review, we explore the current medical therapies for obesity, including all major categories, individual mechanisms of action, pharmacokinetics and pharmacodynamics, adverse effects, risks, and absolute contraindications. Evidence before this study In this placebo-controlled trial, subjects were over the age of 45 years, had a BMI of 27 or above, and established cardiovascular disease.The treatment appeared to counteract the abnormal expression of 591 genes in the spinal cord that had been altered by nerve damage, especially those involved in inflammation, including TNF-α and toll-like receptors.They work by lowering arterial blood pressure, which, in turn, reduces the risk of MACE 7,11.Therefore, to limit the study to a single population, we excluded nicotine dependence to ensure internal validity.The long-term effect of GLP-1 on retinopathy in patients with type 2 diabetes may in fact be beneficial.The box plot on the left displays the observed weight reduction values for Liraglutide (A) and Semaglutide (B) across different age groups.The “GLP-1 response” refers to the effects that GLP-1 has on the body. This can be attributed to the metabolic adaptations that are seen to occur in those with obesity. In situ hybridization studies in animal models demonstrated GLP-1 receptor presence in many other brain areas such as the thalamus, nucleus accumbens, and hindbrain. Early studies demonstrated the anorectic actions of GLP-1 on the hypothalamus 238,239. Numerous studies have demonstrated that dietary macronutrient composition is not the most significant contributing factor for weight loss 44,45,46. Keywords were then refined based on the relevance of the results, and additional terms were searched to survey related areas including “cardiometabolic risk factors”, ‘sarcopenia”, “exercise”, “body mass index (BMI)”, and “appetite”. The search methodology employed in this narrative review was comprehensive and aimed to capture current relevant evidence pertaining to GLP-1 medication use for weight loss and discontinuation of these medications. The cardiometabolic consequences of obesity such as insulin resistance, glucose intolerance, type 2 diabetes, arterial hypertension, atherosclerosis, and dyslipidemia are all stressors on the heart and vascular system 18,19. Obesity has harmful effects on various body systems, most notably on the cardiovascular and endocrine systems, but also on the kidneys, liver, lungs, joints, and immune system . Severe obesity, which is defined as a BMI over 40 kg/m2, is an alarming public health issue . So because of that, I try to avoid surgery, using medications for weight loss. So dedicated weight loss trials came after the diabetes trials. I call them anti-obesity medications because they’re actually more than just the GLP-1 and GLP-1 related therapies that exist to treat patients with obesity. And so it’s really important to address and treat obesity for patients who are living with overweight and obesity. And what is the relationship between weight loss and cardiovascular health? GLP-1 agonists aren’t safe to take during pregnancy. These side effects are more likely to happen when you start the medication or if you’re taking an increased dose. Your healthcare provider will tell you when and how often to take your medication (usually injections). As with all shared decisions, we can start by providing objective information and using a STEPS approach, which outlines a medication's safety, tolerability, effectiveness, price, and simplicity.16 For example, the long-term effects of GLP-1 agonists on the pancreas are unknown (safety). Given the sociopolitical origins of our weight-focused culture, how should we address our patients' desires to achieve a certain weight, even if there is no strict medical need to do so? The cultural fear of weight gain and larger body size has insidious origins. Clinical research and studies uniformly demonstrate their ability to contribute to notable weight loss, improve lipid profiles, lower blood pressure, and reduce cardiovascular risk. The wide use of these drugs and their adverse effects, although rare, need to be considered and calculated by patients who are using the drugs for weight. This will also help the insurance companies in the long run since taking these anti-obesity medications will significantly improve the patient's overall health and lower the risk of complications caused by obesity. Some studies found that LDL-C levels significantly reduced following treatment with liraglutide 1.2 mg/day or 1.8 mg/day (-0.28 and -0.23 mmol/L), exenatide once weekly (-0.13 and -0.17 mmol/L), and exenatide twice daily (-0.25 mmol/L and -6% change from baseline) . Focus on balanced, protein-rich meals with adequate fiber, healthy fats, and low-glycemic carbohydrates. GLP-1–based treatments can help regulate appetite, but nutritional choices still matter. But medications alone are rarely a magic fix. And, of the 20 million adults in the US who suffer from severe obesity, less than 1% will undergo bariatric surgery annually. GLP-1 agonists have demonstrated significant health benefits in controlling weight, blood glucose, blood pressure, and MACE and continue to show promising outcomes in different clinical trials and meta-analyses. This study was corroborated by another study by Diamant et al., where HDL-C levels nonsignificantly changed from the baseline following treatment with exenatide once weekly (0.00 mmol/L) . Similar to research on LDL-C levels and how the use of GLP-1 RAs such as liraglutide and exenatide can affect it, reports found that liraglutide and exenatide treatment also has insignificant effects on HDL-C 66-68. Participants who lost at least 5% of initial weight loss were then randomised. An initial weight loss before randomisation was chosen because the primary aim was to investigate maintenance of weight loss. In the one-year post-treatment phase, there was no contact between study participants and study personnel. All eligibility criteria are available with the protocol.25 All participants who underwent randomisation were invited to participate in the post-treatment study regardless of completion of the active intervention. Eligible participants were adults (aged 18–65 years) with obesity (body mass index 32–43 kg/m2). Even more recently in 2022, a symposium was convened to discuss the state of the science of weight loss maintenance, known as the Pennington Biomedical Scientific Symposium . Other studies confirm the importance of dietary restraint and physical activity in preventing weight regain 247,248. These successful subjects with weight loss maintenance reported high levels of physical activity, high levels of dietary restraint, low calorie, and fat intake, and low levels of overeating (loss of control of eating or disinhibition) . As expected, there was weight regain, but there still was an overall 5.6% net loss of weight by the end of 120 weeks . When switched to placebo there was invariably weight regain, implying that the loss of inhibition of hyperphagia drove this process. Similarly, a treatment course of Semaglutide for 4 months showed a significant reduction of 13% in the carotid intima thickness. In diabetic patients treated with GLP-1 RAs, better blood circulation and improved endothelial function have been recorded 34,35. Over the years, several theories have emerged demonstrating the possible mechanism through which GLP-RAs improve cardiovascular health in the circulatory system. Cardiovascular disease (CVD) is one of the most concerning ailments affecting people worldwide, with an estimated 48.6% of Americans suffering from heart-related illnesses . Others inhibited fat absorption, but were hard to tolerate for many patients because they caused gastrointestinal issues. Some suppressed appetite and made you feel fuller longer, but these could only be used for a limited time due to the side effects. The drugs go by several different brand names, and more are being approved all the time. Nonetheless, while these agents are well-tolerated, they have some side effects, most importantly gastrointestinal, which warrant attention. The concept that body fat storage may be regulated was first proposed by Kennedy et al. through the concept of a “set point” . Obesity may present itself with multiple clinical phenotypes and also varied treatment responses. They carry a boxed warning for people with a personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2. Treatments such as bariatric surgery create hesitancy among patients due to their invasiveness. GLP-1 Receptor Agonists and Weight Regain GLP-1 agonists are being explored as an adjunctive therapy to combine with bariatric surgery to avoid the weight regain that can occur post-surgery 81,82. The metabolic efficacy of bariatric surgery in increasing gut production of GLP-1 to supraphysiologic levels postprandially is considered a major factor in early weight loss . Variations of Roux-en-Y gastric bypass limb lengths have shown potentially increased weight loss and metabolic benefit, but also, possible early and late significant complications 75,76,77. However, as more weight loss is achieved, there is concern for potential adverse effects on muscle quantity, composition, and function. These data can assist clinicians in selecting appropriate medications based on specific adverse reaction profiles of patients. The safety of weight reduction medications has long been a concern, with numerous drugs being withdrawn from the market owing to safety issues 28,29. These findings suggest that within the above ranges, the weight reduction effects of GLP-1RA drugs are independent of baseline weight, BMI, and gender ratio. Effect of GLP-1 Analogues on Gastric Emptying Macie JepsonDo we have enough science to know the long term effects of sticking with us? People who are fit and who exercise and eat right, and maybe a little heavy, it could be muscle and it could also be fat, but that fat might be, you know, fat. So it’s really trying to figure out the consequences of the obesity and how we can then improve it. BMI, which is how we currently define obesity, just does not define that at all. Now the question is how do you identify that in individuals right now you could look at somebody if they look like an apple versus a pear, but you can’t really get an understanding body mass index. These combined effects often result in weight loss. GLP-1 agonists alone can’t treat Type 2 diabetes or obesity. And they’re just one part of your treatment plan if you have Type 2 diabetes or obesity. We have many referrals for these medications, specifically for weight loss and for other reasons. So weight loss through surgery, we know it can be sustainable and has sustainable health benefits actually as well. They found no significant differences between the effects of GLP-1 infusion as PSI or CSI compared with placebo on hunger and satiety ratings 300 min after the meal. The last study by Saxena et al 2021, was a parallel study design that used Liraglutide 3.0 mg (dose started by 0.6 mg per day and escalated by 3.0 mg per week) for six weeks. The third study by Kadouh et al 2020, was a parallel-group study that included 17 participants that used Liraglutide 3.0 mg/daily (starting with 0.6 mg per week to a maintenance dose of 3.0 mg per day) for 16 weeks. All Liraglutide doses showed similar significant effects on overall appetite score (reduced appetite), increased satiety and fullness, and decreased hunger compared to placebo.26 For future development of GLP-1-based therapies (and other therapies) designed for weight loss, as well as for patient-centered treatment optimization, the introduction of more objective and comprehensive ways of assessing muscle health (including accurate and meaningful assessments of muscle quantity, composition, function, mobility, and strength) is important for the substantial numbers of patients who will likely be taking these medications well into the future. A 3-year extension of the SCALE trial showed that persons with overweight or obese and prediabetes taking liraglutide had a reduced risk for developing type 2 diabetes with greater weight loss compared to those taking a placebo While largely successful as an anti-diabetic drug therapy, the effects on both reducing food intake and promoting weight loss in persons with diabetes and animal models prompted further study as an anti-obesity medication 87,88. Four participants had initiated treatment with liraglutide in the post-treatment phase (one in the placebo group, one in the liraglutide group, and two in the exercise group). In the logistic regression analyses, for all participants who had missing body weight data at week 104, we used the predicted body weight value from the linear mixed model to calculate changes from week 0 to 104. Participants were initially recruited for the weight loss and weight loss maintenance phases of the study (week −8 to 52). The primary outcome of the study was the change in body weight (kg) from randomisation to one year after termination of the weight maintenance intervention (week 0–104). It was found that there was no significant difference between the GLP-1 analogous (GLP-1 infusion) group and the placebo group in the proportion of food selected as carbohydrate, protein, fat, or low energy from the food-choice list (data not shown).While GLP1 supplements offer promising results, it’s essential to consider potential side effects and consult healthcare providers before use.These varied treatment responses likely originate from our limited understanding of the mechanisms of weight regulation.Even more recently in 2022, a symposium was convened to discuss the state of the science of weight loss maintenance, known as the Pennington Biomedical Scientific Symposium .More participants who had received exercise had a weight loss of at least 5% of initial body weight compared with liraglutide (OR 2.9; 95% CI, 1.3; 6.6) and at least 10% compared with placebo (OR 3.7, 95% CI, 1.2; 11.1).During the year after termination of treatment (week 52–104), weight regain was 6.0 kg 2.1; 10.0 larger after termination of liraglutide compared with after termination of supervised exercise and 2.5 kg −1.5 to 6.5 compared with after termination of combination treatment.So the apple is what’s called visceral obesity.In cases where studies reported both intention-to-treat (ITT) and per-protocol (PP) results, the ITT analysis results were prioritized for inclusion for conservatism. 2. GLP-1 and Energy Balance Since then, several GLP-1 RAs have been recommended for treatment of diabetes as a second line therapy in view of their clinical efficacies including improved weight loss, low risk for hypoglycaemia, and reduction in glycated haemoglobin (HgA1c). This is the first study, to our knowledge, to assess the impact of antidepressants on the body weight effect of GLP-1 RAs using real-world health record data. Still, GLP-1 medications may have benefits far beyond weight loss – for heart and liver health, for example – which may extend even to people who don’t lose as many pounds as they might have expected, experts say. Related article People using popular drugs for weight loss, diabetes are more likely to be diagnosed with stomach paralysis, studies find Reasons for participants not attending the post-treatment study are shown. In this article, we report the results of a post-treatment study conducted in extension of a randomised, controlled trial.7 The study was conducted at the Department of Biomedical Sciences, University of Copenhagen, and the Department of Endocrinology, Copenhagen University Hospital—Hvidovre. It is, therefore, not established whether people who have completed a long-term exercise program remain more physically active in real-world settings after termination of the supervised program. In contrast to pharmacotherapy, exercise is a low-cost intervention and represents a behavioural change that, in principle, can be continued in a real-world setting after termination of the supervised treatment. However, in recent years, there has been a significant rise in the use of antiobesity medications such as GLP-1 RAs with promising results in weight loss and management 22,23. The effects of exogenous GLP-1 after administration to T2DM patients show improved insulin sensitivity, decreased glucagon concentration, slowed gastric emptying, increased satiety, decreased fatty acid concentration, lowered body weight, and overall decreased hemoglobin A1c (HBA1c) levels. In this narrative review, we have explored the varying effects of these agents on essential metabolic parameters such as blood glucose, cardiovascular health, weight management, blood pressure, and lipid profile in both diabetic and non-diabetic patients. Additionally, these GLP-1 RAs have been explored as an effective means of weight loss, with the STEP clinical trials showing a mean of 5% weight loss at the end of 68 weeks of treatment. Subscribe to Cleveland Clinic Health Essentials The searches were conducted from October 2021 to December 2021 to identify relevant studies. A systematic search was conducted using three electronic databases (PubMed, Scopus, and ScienceDirect) to include all published trials. The primary outcome of the analysis was to evaluate the impact of GLP-1 analogues on appetite, gastric emptying, food preferences, and/or taste in adults with obesity without any other medical diseases. Therefore, the present systematic review aims to summarize the currently available evidence of the impact of GLP-1 analogues on appetite, gastric emptying, food preferences, and taste among adults with obesity. However, high-quality, long-term, large sample size studies are crucial to examine the efficacy and effective dose of GLP-1 analogues intervention. Weight regain often occurs after treatment termination, irrespective of whether the weight loss is obtained with medication or lifestyle-based interventions.19,39 Given the many people who initiate obesity pharmacotherapy worldwide but also terminate treatment again,14, 15, 16, 17 off-treatment assessments are imperative to elucidate the real-world potential of pharmacotherapy and are clinically relevant. Future lifestyle-based treatments during obesity pharmacotherapy may further improve body weight and composition outcomes with an additional focus on strategies and tools to maintain healthy physical activity habits after termination of pharmacotherapy. Conversely, the analyses contrasting liraglutide versus placebo groups showed that the benefits on body weight, body composition, and glucose levels obtained with liraglutide were lost one year after treatment. Research has shown that the use of GLP-1 RAs can modulate cholesterol metabolism, affecting LDL cholesterol (LDL-C), HDL cholesterol (HDL-C) levels, and total cholesterol (TC) levels in patients with cardiometabolic diseases. Atherosclerosis can develop in vital blood vessels in people as young as 15 years and increase in prevalence and extent with age up to 34 years . As analyzed by the recent meta-analysis of these trials, there is a 32% prevalence of heart-related diseases in T2DM patients. Therefore, we investigated whether weight loss and improved body composition are sustained better at 1 year after termination of active treatment with glucagon-like peptide-1 (GLP-1) receptor agonist, supervised exercise program, or both combined for 1 year.Qsymia has demonstrated overall efficacy for weight loss maintenance, achieving sustained weight loss of 9-10% at the 108-week mark compared to 1.8% for placebo .In terms of constipation, except for Danuglipron, which was lower than the placebo, the incidence rates for other GLP-1RA drugs were similar to or higher than those for the placebo.No time frame determines; studies measured appetite, gastric emptying, food preferences, and/or taste as a primary or secondary outcome.An off-treatment extension of a study of semaglutide, a receptor agonist of the incretin glucagon-like peptide-1 (GLP-1), showed that about two-thirds of the lost weight was regained within the first year after treatment termination.These changes have meaningful long-term health benefits, even if weight loss is slower than hoped.Weight regain often occurs after treatment termination, irrespective of whether the weight loss is obtained with medication or lifestyle-based interventions.19,39 Given the many people who initiate obesity pharmacotherapy worldwide but also terminate treatment again,14, 15, 16, 17 off-treatment assessments are imperative to elucidate the real-world potential of pharmacotherapy and are clinically relevant. For instance, those with high levels of physical activity are more successful at weight loss maintenance 257,258,259. Specifically, a decrease in processed and ultraprocessed food consumption would be beneficial for weight loss maintenance. The Pennington symposium highlighted potential alternative approaches for nutrition management that may be beneficial for weight loss maintenance. However, as detailed in this review, calorie reduction generally leads to short-term weight loss, with poor success rates for long-term weight loss maintenance. Not surprisingly, food composition is often an area of question by both scientific communities and the food industry to determine the right “mix” of macronutrients to facilitate weight loss and weight loss maintenance. In summary, GLP-1 RAs have been well placed as the forerunner of pharmacological intervention for obesity in both diabetic and nondiabetic population (Table 2). In summary, there is no direct trial evidence of GLP-1 RAs' effects on prevention of CKD in nondiabetic population (Table 2). GLP-1 RAs reduced blood pressure after prolonged treatment, specifically lowering systolic blood pressure by 3-4 mmHg, which is renoprotective. HARMONY and PIONEER 6 reported no change in eGFR with albiglutide and semaglutide, respectively 23, 24. Certain health conditions can make weight loss more difficult, even with medication support. Continued weight loss generally requires mindful nutrition choices and regular movement, even when medications are being used as part of the plan. In some cases, the reason weight loss is slower – or not happening at all – may have less to do with the medication itself and more to do with how the body is responding to it. But but as a doctor, what other factors are you using to determine someone’s health and who’s a person, maybe, who’s not at their doctor? You hit on one thing that I think is the society, we’ve gotten to a place where we measure someone’s health solely based on the scale. I think, you know, again, it is a kind of panacea for because we find that so many cardio metabolic conditions are improved with these medications. There are plenty of people who, if you try to get them down to a BMI of 25 or less, that will make them very frail and very, you know, predisposed to falling and breaking a hip or hurting themselves. But right now they’re healthy. It considers the finding of the clinical trials, and below will clarify the systematic review question and PICOTS, study eligibility, search strategy, data collection and extraction, and validity assessment of risks of bias in included studies. GLP-1 RA-supported weight programs can lead to 6-17% mean weight loss in adults without diabetes but only 4-6% in people with diabetes. During GLP-1-assisted weight loss, patients are advised to consume one gram of protein/kg of their ideal body weight to prevent lean-mass loss, which can reach up to 50% in protein-deficient individuals. GLP-1 agonists demonstrate efficacy for weight loss maintenance, but only while the patient is continuing to use the medication. Amylin analogs such as cagrilintide are being explored for obesity treatment in concert with GLP-1 drugs . A multi-agonist approach is a likely road for the future of anti-obesity drug development involving novel receptors such as glucagon and amylin possibly with even more profound weight loss 286,287. We are also cautious about using these drugs if you’re on active cancer therapy and experiencing side effects such as nausea and vomiting; GLP-1 agonist therapy can sometimes worsen those. Guidelines from anesthesia and surgical societies recommend holding the weekly formulations of these drugs for at least a week before surgery, so careful planning is required if a patient is using these therapies. The primary concern is the availability of these drugs for the patients who need them. There was an early study a couple of years ago that indicated a possible link to thyroid cancer, but that study had some limitations, and subsequent studies have shown that there is likely not a link there. It is worthwhile to note in both studies all participants were prescribed a reduced calorie (500 kcal/day deficit) and increased physical activity 150 min/week) regimen, which was insufficient to help preserve the initial weight loss. Randomized double-blinded placebo-controlled withdrawal studies were performed in both semaglutide and tirzepatide with crossover to placebo at 20 weeks and 36 weeks, respectively 242,243. Incretin-based medications and other anti-obesity medicines target hunger, therefore fostering both weight loss and weight loss maintenance. Amylin analogs such as cagrilintide are being explored for obesity treatment in concert with GLP-1 drugs .For example, many people will go and find that the doses do not match the same doses that you get for a prescription drug.The effect seems principally within the CNS, but combination treatment of GLP-1 with other targets appears to further improve weight loss in early clinical trials.Everybody with these medications is kind of funny.The GLP-RAs have also been found to affect blood pressure and cholesterol, benefiting cardiovascular health in general.Incretin-based treatments such as glucagon-like peptide-1 (GLP-1) receptor agonists are approved for the treatment of obesity and type 2 diabetes.And they’re just one part of your treatment plan if you have Type 2 diabetes or obesity.Small and periodic meals, as well as structured intermittent-fasting patterns, can lead to comparable weight loss after six months. GLP-1’s plays a critical role in managing how the body processes food, influencing insulin secretion, blood sugar levels, and hunger signals. Prescribing a GLP-1 agonist may be appropriate for these patients. We can also redirect the conversation toward health-promoting behaviors. These medications are expensive (price), and injections are more complex than oral medications (simplicity). Adverse effects can include nausea, vomiting, diarrhea, and bloating due to gastroparesis (tolerability). Because if we if we talk about just some unexpected side effects, people are still going to want to go for the cheaper, faster route. So you have to really be mindful and manage the side effects, manage the effects of the drugs in order to get the best benefit. Make sure that you also that you eat and you feel your body because a lot of people won’t want to eat on these medicines, they feel fatigued. And frailty is to maintain muscle mass and preserve that muscle mass, whether it’s through exercise, weight training, protein supplementation. So, we need to carefully monitor their use in patients who are on active chemotherapy, as sarcopenia and weight loss can make it harder for patients to tolerate chemotherapy. These drugs cause dramatic weight loss, some of which is also a significant muscle mass loss. There has also been some concern that some of the side effects could increase the risk of pancreatic cancer, but so far, studies have not shown that to be the case. For example, obese people are often at risk for injuries when they start a new exercise routine, which can set them back or ultimately cause them to give up on it. Hence, government officials, pharmaceutical companies, physicians, and public health advocates need to come forward to collaborate and make an effective policy on the pricing, insurance coverage, manufacturing, distribution, and availability of these medications for the greater good of the people. This means that GLP-1 could help treat osteoporosis and similar bone issues, particularly in people with T2DM. In osteoporosis, GLP-1 RAs such as exendin-4 can help by increasing osteocalcin levels, a protein essential for bone health. For instance, liraglutide has been shown to reduce oxidative stress in macrophages through GLP-1 receptor signaling . So there is such a thing as metabolically healthy obesity, people with excess body weight that don’t manifest the diseases that relate to obesity.A 16-week randomized trial compared once-daily SC injected liraglutide vs placebo in patients with schizophrenia who incurred weight gain and prediabetes after taking olanzapine or clozapine.5 Significantly more patients taking liraglutide than placebo developed normal glucose tolerance (64% vs 16%), and body weight decreased by a mean of 5.3 kg.Therefore, focused continued physical activity after the termination of pharmacotherapy is advisable for healthy weight maintenance.During GLP-1-assisted weight loss, patients are advised to consume one gram of protein/kg of their ideal body weight to prevent lean-mass loss, which can reach up to 50% in protein-deficient individuals.GLP-1’s plays a critical role in managing how the body processes food, influencing insulin secretion, blood sugar levels, and hunger signals.Studies have shown that GLP-1 receptor agonists significantly aid weight loss.While your healthcare provider will of ... Now, there is a way to try to mitigate that and to try to, you know, keep maintenance being off the medications. And like I said, if you stop them, there is weight regain. The medications are only going to work if you’re taking them. When I hear people talk about, you know, I can’t get off of them, it’s interesting. I’m afraid that I’ll lose some weight, that it will age me. New incretin-based obesity medications have shown significant therapeutic potential. Weight regain during the one-year post-treatment phase was 6 kg larger after GLP-1 receptor agonist treatment compared with after supervised exercise. In contrast, most studies on physical activity treatment programs have reported sustained increases in physical activity levels after termination of the supervised program. Between Dec 17, 2018, and Dec 17, 2020, 109 participants attended the post-treatment study. We conducted a post-treatment study in extension of a randomised, controlled trial in Copenhagen. Similarly, Semaglutide is both Ozempic for diabetes and Wegovy for weight loss, and Tirzepatide is Mounjaro for diabetes and Zepbound for weight loss. So Liraglutide is both Victoza for diabetes and Saxenda for weight loss. We see benefits from the body weight and all the different things that weight loss impacts, as well as heart failure and many other conditions. Due to limited bioavailability, most GLP-1 agonists require subcutaneous (SC) injections (the sole exception is the Rybelsus brand of semaglutide, which comes in a daily pill form). In addition to GLP-1 agonism, some medications in this family (notably tirzepatide) also agonize a second hormone, glucose-dependent insulinotropic polypeptide, which can further induce insulin secretion as well as decrease stomach acid secretion, potentially delivering an even more substantial reduction in appetite and weight. However, the magnitude of impact for most of these agents to reverse iatrogenic weight gain tends to be modest, particularly once significant weight gain (ie, ≥7% of initial body weight) has already occurred. More than one-half of individuals with severe mental illnesses are obese or overweight,1 resulting from multiple factors that may include psychiatric symptoms (eg, anergia and hyperphagia), poor dietary choices, sedentary lifestyle, underlying inflammatory processes, medical comorbidities, and iatrogenic consequences of certain medications. Obesity and overweight, with or without metabolic dysregulation, pose vexing problems for many patients with mood, anxiety, or psychotic disorders. Stacey's journey in healthcare started over a decade ago as a volunteer firefighter and paramedic, leading to a multifaceted career in nursing. Take the first step toward a healthier future today. Together, you will develop a personalized plan – whether that involves GLP-1 therapy, alternative medications, or other appropriate approaches – to support long-term success. Since the GLP-1 agonists (semaglutide) have been approved for weight loss therapy, a new era for obesity management has developed rapidly. More data and long-term studies are needed to determine the side effect profile and the long-term effects of these medications on the human body . Given their effectiveness in controlling blood glucose and HbA1c levels, with additional weight loss benefits and minimal intrinsic risk of hypoglycemic episodes, GLP-1 RAs are now considered the first-line injectables for optimal glucose control in diabetic patients even before insulin treatment . Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), especially semaglutide (famously known as Ozempic® or Wegovy®), have become very popular in recent years for weight loss, even though their initial indication is for the management of the patient with diabetes mellitus. The results provide quantitative data for the evaluation of new drugs and, optimization of treatment strategies for people with obesity. The selected 55 studies included a total of 16,269 participants, with an average age range from 29.5 to 64.7 years, and a median age of 53.6 years. When heterogeneity was obvious (I2 ≥ 50 %), a random-effects model was used to summarize the RRs; otherwise, a fixed-effect model was applied. Heterogeneity among studies was assessed using the I2 statistic, with an I2 value of 50 % or higher indicating obvious heterogeneity. As most of the included studies only reported dropout rates and the incidence of adverse events at the endpoint, we were unable to establish a time-course model for them. This process was repeated 10,000 times to estimate the median and 95 % confidence interval (CIs) of the drug effects at each time point for each subgroup. Embrace healthy fats. It is worth noting that the present analysis did not assess a traditionally weight-neutral antidepressant, such as fluoxetine, as fluoxetine is less frequently used first line and thus would have been more likely to create substantial differences in the baseline population. Alternately, there may be a diminished capacity to lose weight with GLP-1 RAs as a result of the interaction. In addition, there is the possibility for confounding by indication, which is somewhat mitigated by PSM, to produce a baseline study population with a similar rate of comorbidities and medication use. Therefore, we investigated the sustainability of exercise-based and pharmacology-based single or combination treatment for weight loss maintenance in a real-world situation. It is the first study to directly compare body weight changes after physical activity and obesity pharmaceutical interventions and investigate the combination of both. Despite the sustained weight and fat reduction after termination of combined exercise and liraglutide compared with after termination of liraglutide alone, some weight gain after treatment was not entirely prevented. Although the exercise program in our study was not specifically focused on maintaining habits after the intervention, a sustained effect on healthy weight was present one year after the intervention was completed. More participants who had exercised engaged in moderate- or vigorous-intensity physical activity in the week prior to the post-treatment assessments, compared to liraglutide alone, which was also confirmed in the questionnaires. For example, with injectable Semaglutide, at doses of 0.05 mg, 1.0 mg, and 2.4 mg, the weight reduction effects at 52 weeks were1.21 kg, 7.6 kg, and 9.05 kg, respectively (Fig. 4). The graph on the left represents the 95 % CIs of the typical pure effect of weight reduction over 52 weeks, with the yellow stripe indicating Liraglutide and the purple stripe representing other drugs. Additionally, we conducted subgroup analyses based on receptor specificity to explore the differences in weight reduction effects among mono-agonists, dual-agonists, and tri-agonists. GLP-1 RAs have shown consistent results in managing blood glucose levels by lowering HbA1c with minimal hypoglycemic risk and increasing insulin production and synthesis. Several pharmacologic treatments to maintain or improve muscle mass designed in combination with GLP-1-based therapies are under development. Nevertheless, factors such as older age and prefrailty may influence the selection of appropriate candidates for these therapies because of risk for sarcopenia. So, it will be interesting to see what we continue to learn about how these drugs work and what the long-term effects might be on other organ systems. However, they also have some side effects, with many patients experiencing nausea, vomiting and diarrhea. But what are they, how do they work and are there things current cancer patients should be aware of if they’re considering these drugs? A 56-week RCT of liraglutide 3.0 mg daily, used as an adjunct with a reduced calorie diet and increased physical activity in nondiabetic overweight or obese adults demonstrated a significant averaged weight reduction by −8.4 kg ± 7.3 kg , corresponded to an averaged reduced BMI of −3.0 ± 2.6 kg/m2 . A systematic review has summarised the evidence that weight loss of 5 to 10% reduce obesity-related complications and improve quality of life. In LEADER, liraglutide decreased poor renal outcomes by 22% and in SUSTAIN-6, semaglutide reduced poor renal outcomes by 36%, while post hoc analyses showed that their antialbuminuric effects were independent of their glucose-lowering effects. This contrasts with physical activity interventions, where increased physical activity in principle can be continued in a real world-setting after intervention termination and, thus, treatments effects can be maintained. Therefore, focused continued physical activity after the termination of pharmacotherapy is advisable for healthy weight maintenance. This notion could also explain the observed improvements in resting heart rate and physical functioning after termination of combined exercise plus liraglutide compared with after termination of liraglutide alone. In addition to its effect on body weight, a variety of health benefits have been ascribed to it. Regular physical activity is also recommended as a component of weight loss programs not only for energy expenditure, but for cardiometabolic health as well . In a randomized study of overweight adults, following a low-fat or high-fat diet with average or high protein resulted in an average 7% weight loss at 6 months, irrespective of diet type . Exceeding 6-12 months of use may have undesired effects by increasing LDL cholesterol and cardiovascular risk in some studies, but others have found no difference 50,51,52,53. Clinical studies have supported this with GLP-1 receptor analogs such as liraglutide and semaglutide in both weight loss and weight loss maintenance trials. The landmark GLP-1 drug trial for semaglutide, STEP 1 (semaglutide treatment effect in people with obesity), demonstrates a significant loss of total lean body mass , which has been further corroborated by other investigators . Since the FDA approval of liraglutide for weight loss in 2015, the use of this class of medication has exploded, particularly over the last few years with the availability of weekly GLP-1s including tirzepatide and semaglutide. It helped one-third of the non-diabetic study patients achieve a loss of 10% of their body weight and also helped them sustain their weight loss for upwards of 1 year . One year after treatment termination, participants who had received exercise alone or in combination with liraglutide reported the highest levels of moderate-to-vigorous-intensity physical activity. Participants who previously received the combination treatment had improved scores of physical functioning, less limitations due to physical health, and energy/fatigue compared with liraglutide alone. The improvements in HbA1c and fasting glucose that were obtained with liraglutide alone and combined with exercise were lost one year after treatment termination. The combination treatment resulted in decreased fat mass compared with liraglutide alone (Fig. 4E and Table S8) and decreased waist circumference compared with placebo and liraglutide alone (Fig. 4F). The assessment of the risk of bias within these studies revealed the following results.16–18,20,22–29 Briefly, the generation of random allocation for participants was unclear in eight, and low risk of bias in four studies. In addition, the summary of the risk of bias is shown in Figures 2 and 3 for all included studies. However, four studies included only males,16,27–29 and the remaining eight included both genders.17,18,20,22–26 These studies were performed in different countries; three studies were conducted in the United States,17,24,25 one study in the Netherlands,26 three studies in Sweden,20,27,28 two studies were conducted in Denmark16,29 f, two in the United Kingdom,18,22 and one in Germany.23 Characteristics of this systematic review are in Table 2. Find out what the research says about who's at higher risk of developing it and how to slim down with lifestyle changes. De-identified participant data that underlie the results reported in this article will be made available for research collaboration purposes upon request and approval of the requested use of data by the corresponding author and will require the completion of a data processing agreement. All authors contributed to subsequent drafts and interpretation of data. This study provides a quantitative evaluation of the efficacy and safety of GLP-1RAs and offers valuable insights into the assessment of new drugs for weight reduction.Many people begin their weight loss journey with high hopes — especially when prescribed newer treatments that target metabolic pathways.GLP-1 RAs work by mimicking the effects of endogenous GLP-1, a hormone that slows gastric emptying, suppresses appetite, and enhances insulin secretion in a glucose-dependent manner.Clinical trial outcomes will determine whether these will be useful either on their own or in conjunction with GLP-1 agonists.Patients should be aware of these potential unwanted effects and, to minimize loss of muscle mass, encouraged to participate in resistance exercises and increase protein intake .Physical activity and sedentary time were objectively measured in the week leading up to the post-treatment study visit with wrist-worn accelerometers (GENEActiv, Activinsights Ltd.) analysed with the R-package GGIR v.2.9–029, 30, 31 and subjectively with the International Physical Activity Questionnaire.32Making sure you’re getting protein in your body and making sure that you’re building that strength to get through it. They’re designed for long term weight management for people who need it. And then there’s a lot of, people who regain the weight and are unable to sustain the lifestyle. Ian Neeland, MDSo I think it is first line in certain situations and certain patient contexts, lifestyle is always the cornerstone of weight loss therapy, right? I’ve seen several situations where young people who started the medications from a compounding pharmacy have had major side effect issues. There have been other medications have been tried in the past, both short term and long term management of weight. So it’s important to talk about the truths and the myths of these medications and really provide the facts for people to make their own decisions with their doctor. So obesity, which is what we define as having excess body fat or excess adiposity, is a chronic medical disease and unfortunately leads to many different downstream problems. GLP-1 analogues proved to be an effective weight management therapy to overcome obesity and its physiologic and metabolic complications. Second, the Cochrane Collaboration risk of bias tool was used to assess the risk of bias and the quality of evidence for all studies included. Taking injectable Semaglutide (1.0 mg) as an example, the efficacy at 26 weeks, and 52 weeks was 5.77 kg, and 7.57 kg, respectively, representing 49.3 %, and 64.7 % of its maximum effect (Fig. 5). The results indicated that Liraglutide exhibited the fastest onset, reaching an efficacy plateau (80 % of the Emax value) by week 17, whereas Tirzepatide showed the slowest onset, requiring 46 weeks to reach the efficacy plateau. The shaded gray area represents the range of doses administered in the included studies, while the plotted points indicate the maximum, median, and minimum drug doses observed across the studies. This systematic review was undertaken to summarize the currently available evidence of the effect of GLP-1 analogues on appetite parameters, gastric emptying, food preferences, and taste in adults with obesity. Measured taste by a standardized nutrient drink test; the period was 16 weeks. Two studies (one Liraglutide and one GLP-1 infusion) investigated the effect of GLP-1 analogues on taste using different methods.16,17 The first study by Näslund et al 1998, was a crossover study in which they used GLP-1 infusion (0.75 pmol GLP-1/ kg−1/min−1) and measured food preferences by the forced-choice list method, which is designed to reveal a specific preference for proteins or carbohydrates; over two occasions, five days apart. This can be attributed to the persistent effects of metabolic adaptation, the phenomena seen in weight regulation that may cause weight regain and potentially a weight loss plateau . Early case reports called into question appropriate fasting times for pre-procedural and operative fasting due to retained gastric contents and risk of aspiration in patients taking GLP-1 medications and compounds 213,214. Secondarily medically induced weight loss, particularly when totaling in excess of 5% of total body weight has demonstrated effectiveness in improving fertility . The rapid weight loss can be visualized in many areas of the body and one of these manifestations known as “Ozempic face” occurs when fat pads in the face are rapidly depleted 177,178. We were not able to fully account for use of medications which may result in weight gain or diminished weight loss (eg, insulins, sulfonylureas) among escitalopram/citalopram users, for the duration of antidepressant use prior the initiation of the index GLP-1 RA, medication dosing, or medication adherence. Also, in relation to body weight, the study was dependent on assessing pre and post weight, but was unable to assess the variance in the change of weight, thus precluding inferential statistics on mean change in body weight. Moreover, with regard to body weight, there is no reason to expect, based on the study populations, that one group might be more predisposed to outdated body weight assessment. Achieving success with pharmacologic treatment and then weaning to avoid future negative effects would be ideal. A significant disadvantage of using these medications is the high rate of weight regain when they are discontinued. Treating obesity is challenging and calorie restriction often leads to rebound weight gain. Health consequences of excess weight include cardiovascular diseases, type 2 diabetes, dyslipidemia, and increased mortality. Talk to your healthcare provider to see if a GLP-1 agonist is right for you. The energy-dense nature of fat makes it an efficient means of storing excess energy intake and thus the body favors fat for keeping energy in reserve 91,92. The intragastric balloon is an anti-obesity intervention in which a silicone balloon is endoscopically deployed and filled with saline and inflated for 6 months. Patients are advised to consume a low-fat diet to combat the side effects of oily stool . Previous studies have shown that the efficacy of weight reduction medications is influenced by baseline weight, with individuals having higher baseline BMI experiencing larger reductions in weight . Overall, a 52-week treatment duration generally allows all the GLP-1RA drugs currently studied to reach their efficacy plateaus. The duration of the clinical trials included in this study ranged from 6 to 104 weeks, with a median treatment duration of 26 weeks. 1. Factors That Avert Weight Regain Certainly, teaching patients to be mindful of their eating and to consume adequate protein can contribute to weight loss maintenance success and overall health . The effects on weight, cardiovascular health, and other parameters of decreasing the dose or pausing and resuming the use of GLP-1 agonist is an area where evidence-based studies are needed. The authors of this study pointed out that there appears to have been a slowing of weight regain towards the end of the study, implying a weight loss plateau below the initial pre-treatment weight. It is interesting to note that an extension study of semaglutide was performed to 120 weeks, but treatment was discontinued at 68 weeks. Open-label clinical trials exploring the effect of exenatide on body mass in overweight or obese women with PCOS showed a significant reduction in body weight, ranging from -3.1 to -6 kg and a corresponding decrease in BMI between -1 and -3.1 kg/m2 . The trial of 150 women with PCOS with impaired fasting glucose and/or impaired glucose tolerance demonstrated a prediabetes remission rate of 64% with combined treatment, 56% with exenatide only and 32% with metformin only . This trial featured by exenatide and metformin effects on the remission of prediabetes, a prevalent comorbidity of PCOS . This review investigates the various pharmacologic treatments for overweight and obesity in adults, especially glucagon-like peptide 1 (GLP-1) agonists. Recent studies have shown that pharmacologic weight loss with glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and combination therapies is approaching magnitudes achieved with surgery. This study found that the dropout rates for injectable Semaglutide, Liraglutide, Mazdutide, Retatrutide and Tirzepatide were significantly lower than those for the placebo, suggesting that these drugs have a favorable risk-benefit ratio. However, in the covariate analysis of this study, no significant effects of baseline weight, baseline BMI, or proportion of males on the weight-reducing impact of GLP-1RA drugs were found. Table 1. For Contrave, a weight loss plateau seems to occur for all the COR studies around 32 to 36 weeks with overall weight loss around 8 to 9%. Anti-obesity medications such as Contrave (bupropion/naltrexone) or Qsymia (phentermine/topiramate) also appear to be effective for maintaining weight loss . Pharmacological treatments for weight loss have expanded and, while GLP-1 agonists are the focus of this review, other choices are available and summarized here. These include favorable effects on heart and brain health and decreased diabetes risk 55,56. GLP-1 medications are typically started at a lower dose to minimize side effects and then gradually increased. Even so, it’s still possible for some to experience limited weight loss while using Zepbound®, and understanding why this happens is an important part of finding the right approach. Achieve your weight-loss goals with GLP-1 treatments like Wegovy® and Zepbound®, guided by licensed providers every step of the way. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are a preferred medication class for diabetes and obesity treatment given their weight loss effect; however, it is not known how antidepressants impact this effect. Most of the existing empirical data on weight loss with GLP-1 agonists come from studies of individuals who are overweight or obese, with or without type 2 diabetes, rather than from studies using these agents to counteract iatrogenic weight gain. An analysis of health insurance claims released Tuesday found that most people using GLP-1 medications – about 58% – were on their treatment plan for less than 12 weeks, falling short of a key benchmark in the weight-loss treatment timeline. Demand for Wegovy and other GLP-1 drugs used to treat obesity and diabetes has skyrocketed, but a new report suggests that many people may not be sticking with their weight-loss treatment long enough. Just answer a few questions about your weight loss journey so far, and if you're eligible, you’ll be able to schedule a virtual appointment with a provider who can help you move forward with confidence. Through the LifeMD Weight Management Program, you will work closely with a healthcare professional who will assess your health history, medications, lifestyle habits, and goals. Adjusting your approach is not about "giving up." It is about finding what works best for your body and supporting your long-term health in the most effective way possible. Early studies demonstrated the anorectic actions of GLP-1 on the hypothalamus 238,239.Despite this, animal studies have demonstrated decreases in pancreatic secretion in response to GLP-1 elevation, therefore the mechanism behind this potential interaction of GLP-1 receptor analogs and pancreatitis remains elusive .Moreover, the SUSTAIN trials, which studied the effects of semaglutide in those with T2DM, also demonstrated significant improvement in risk factors, with a substantial 26% relative reduction in cardiovascular events such as nonfatal myocardial infarction and stroke 13,14,29.The landmark GLP-1 drug trial for semaglutide, STEP 1 (semaglutide treatment effect in people with obesity), demonstrates a significant loss of total lean body mass , which has been further corroborated by other investigators .There’s a low risk of mild low blood sugar (hypoglycemia) episodes if you take a GLP-1 agonist.The last study in the GLP-1 infusion section has been done by Bergmann et al 2019.Definitions of weight regain may vary, namely the duration and how much is considered significant.The concept that body fat storage may be regulated was first proposed by Kennedy et al. through the concept of a “set point” . Allowing enjoyable foods in moderation, like a few times per week, can help reduce cravings and the food noise that can interfere with your weight-loss goals. Better blood sugar and insulin balance can make weight loss easier. Add soluble fiber-rich foods, such as beans, lentils, berries, and oats, to your diet to support weight loss and nutrient intake. Another weight loss benefit is GLP-1’s effect on the brain’s reward system, where it can reduce cravings by quieting the running thoughts about food. Most are FDA-approved not specifically for weight loss but for patients with type 2 diabetes (defined as a hemoglobin A1C ≥6.5% or a fasting blood glucose level ≥126 mg/dL). Yet meta-analyses have shown that although results are significantly better than placebo, overall long-term weight loss from metformin alone tends to be rather modest (3 Psychiatrists (and other clinicians who prescribe psychotropic medications that can cause weight gain or metabolic dysregulation) therefore need to become familiar with alternative or adjunctive weight loss options. The data from Dandelion Health showed that the 10% of people with the best response to GLP-1s had results that mirrored what clinical trials found, but the 10% with the least success with the treatments had no weight change, or even an increase in weight, over time. There’s no “best” way to manage Type 2 diabetes or obesity. It can become a serious risk if you take GLP-1s with other medications that lower blood sugar, like sulfonylureas or insulin. Animal studies show that these medications cause developmental abnormalities in the fetus. Most people know that losing weight has numerous benefits, but making major lifestyle changes can be extremely difficult. Most patients found ROSE-010 preferable to prior treatments, with female patients responding more effectively. In another study, liraglutide alleviated LPS-induced visceral pain in rats by decreasing intestinal inflammation and IL-6 in the colon through nitric oxide response . In a different diabetic neuropathy model, the combination of oral amitriptyline and subcutaneous liraglutide and a formulation combining both drugs showed significant improvements in pain and inflammation markers in the sciatic nerve . Another study found that liraglutide also reduced the activation of microglial cells in the brain's cortex and thalamus in diabetic rats by lowering the expression of NLRP3 protein, a marker of inflammation in brain microglia . Every person is unique and so is each treatment plan. You should have regular appointments with your healthcare provider when taking a GLP-1 agonist to assess how well it’s working. Without proper treatment, severe hypoglycemia can be life-threatening. There’s a low risk of mild low blood sugar (hypoglycemia) episodes if you take a GLP-1 agonist. If you become pregnant while taking the medication, see your healthcare provider immediately. GLP-1 RAs provide a multifactorial and practical approach to managing T2DM and related metabolic conditions, along with obesity, dyslipidemia, and hypertension. Paramount cardiovascular outcome studies such as SUSTAIN and LEADER trials describe reduced MACE, signifying GLP-1 RAs as a valuable additive in cardiometabolic management. Heart health benefits are even of interest; trials show that GLP-1 RAs decrease inflammatory markers, improve endothelial function, and decrease arterial stiffness. GLP-1 RAs’ distinct and unique mechanism of enhancing insulin release in response to glucose, increasing satiety, and slowing gastric emptying can be attributed to the previously mentioned benefits of weight management and glycemic control. A GLP-1 analog, ROSE-010, was tested in IBS patients for pain relief, effectively increasing intestinal muscle movement . Plus, a lot of compounding pharmacies will add additional elements like B12, because it kind of helps people feel better. For example, many people will go and find that the doses do not match the same doses that you get for a prescription drug. So people were unable to get it through a standard, you know, prescription coverage for insurance. And yet people are really focused on where they can get it, you know, the easiest route that they can take. They also have a lot of metabolic benefits because they increase secretion of the body’s own insulin, which reduces blood sugar and, impacts kind of vascular health as well as endothelium. So these medications reduce appetite, reduce interest in food, make people less hungry. And was approaching the amount of weight loss one could achieve with bariatric surgery. Generally, the risk of hypoglycaemia in patients taking GLP-1 RAs alone was low, and similar across all GLP-1 RAs 66, 69. In another study, gastric half-time emptying was delayed in most diabetic patients without preexisting gastroparesis after commencing GLP-1 RAs, while those with preexisting gastroparesis were minimally affected . In summary, there is some trial evidence of GLP-1 RAs' effects on prevention of PCOS through weight reduction in nondiabetic population (Table 2). Exenatide compared with metformin demonstrated a significantly greater number of spontaneous pregnancies in the exenatide group, after 24 weeks of treatment . In the post hoc analyses of individual patient-level data combined from SUSTAIN-6 and PIONEER 6, semaglutide showed no difference on MACE in patients with baseline HF . The convenience of once-weekly semaglutide and dulaglutide may improve the adherence to treatment and reduce the burden of the daily administration as other hypoglycaemics. GLP-1 RAs are also recommended for obesity and overweight management in nondiabetic patients except in Chinese guideline .