GLP-1 agonists can affect gastric emptying, which may increase the risk of pulmonary aspiration in patients undergoing monitored anesthesia care or general anesthesia as part of procedures performed in a catheterization laboratory. Semaglutide recently gained FDA approval for treatment of Type II diabetes mellitus and chronic weight management 55,56. A key pathogenic driver of NASH is insulin resistance which is a shared characteristic with type 2 diabetes and obesity. The effects of GLP-1 in CKD patients, irrespective of the presence of diabetes, remain controversial. For many patients, effective GLP-1 medications have required daily or weekly injections, a real barrier to treatment. Orforglipron’s ATTAIN-2 trial showed participants lost an average of 10.5% body weight while reducing A1C by 1.8%—all with a once-daily pill taken anytime. The rise of GLP-1 therapies and the evolution of obesity treatment Over 40% of adults in the U.S.... As the new year begins, many patients refocus on weight management and long-term health goals. Diabetic patients treated with semaglutide (Ozempic) showed dose-dependent weight loss with an average ~6 kg at a 2 mg dose with 40% of patients losing more than 10% of their weight (1). Lastly, there are many GLP-1 agonists currently being researched for PD treatment, and other similar drugs have shown less promising results compared to lixisenatide. A recent clinical trial, published in the New England Journal of Medicine, tested whether a GLP-1 agonist called lixisenatide could be a new treatment approach for people in the early stages of Parkinson's. Rather, the firm is interested in working with drug innovators on new peptide-based drugs for diabetes, weight loss, and other indications. Meanwhile, multi-agonists are pushing the boundaries of what’s medically possible, with drugs like retatrutide delivering weight loss comparable to bariatric surgery. Oral semaglutide hit 17.4% in people without diabetes, while orforglipron achieved 14.7% in a more challenging population with both obesity and type 2 diabetes. Habener and colleagues made cDNAs from the Brockman bodies, and in 1982 reported that glucagon is a cleavage product of a 124 aa precursor protein that also encoded a previously unknown 34 amino acid peptide (3). This was because in contrast to mammals where the islets of Langerhans are embedded in the exocrine pancreas, in fish, the islets reside in a separate organ known as Brockman bodies, thus providing an enriched source of glucagon-producing cells. Subsequent studies using radioimmunoassays showed that glucagon-like peptides in the intestine were released in response to glucose (5), raising the possibility that a product of the glucagon gene might function as an incretin. “Incretine” would remain undiscovered until 1986 when Habener and Mojsov identified GLP-1(7-37) in intestine as a cleavage product of the precursor for the hormone glucagon (3, 4). However GIP did not show efficacy in diabetic patients so the search continued (1). Research suggests these drugs could reduce brain inflammation, improve blood vessel health and even protect neurons. GLP-1s (glucagon-like peptide-1 receptor agonists) are medications designed to help the body regulate blood sugar levels. This includes developing screening tools to identify patients at higher risk for complications like pancreatitis or gallbladder issues. Researchers are working on strategies to reduce the risk of more serious side effects as well. Our data show that another 14.0 percent of survey respondents expressed an interest in taking GLP-1 agonists. Finally, we provide the first population-level estimates of side effects experienced by those who have taken GLP-1 agonists. Members of the panel are drawn using probability sampling methods, and the data are weighted to reflect the demographic diversity of the U.S. population. Breathing Danger: Study Links Air Pollution to Lewy Body Dementia Risk These new chemical methods, which are still in use, provided a simple means for synthesizing a large number of glucagon variants.This finding may indicate that the effect of Semaglutide on heart failure goes beyond weight.For many patients, effective GLP-1 medications have required daily or weekly injections, a real barrier to treatment.Semaglutide is currently contraindicated in patients with a personal or family history of medullary thyroid cancer or multiple endocrine neoplasia .Novo Nordisk holds patents on semaglutide in the US until 2032.She found that while there was abundant glucagon in the pancreas, only larger molecular weight forms of it were seen in intestine.The success of GLP-1 clinical trials is rapidly advancing obesity treatment, with drugs now delivering bariatric surgery-level weight loss without surgery.While semaglutide thus far appears to be quite safe, the nausea that it causes is clinically significant, leading many patients to discontinue treatment (1). The potential applications of GLP-1 drugs continue to grow. Just when we thought we’d seen the pinnacle of metabolic medicine with drugs like Wegovy and Mounjaro, researchers are pushing the boundaries even further. The world of GLP-1 drugs is evolving at breakneck speed. That helps explains why in the medical literature, compared to any other way of eating that didn’t involve portion control, a whole food, plant-based diet has been shown to lead to greater average weight loss than any other diet. With the right tools, we can ensure that future arrives as quickly and safely as possible for the millions waiting for these treatments. With 15+ years in computational biology, I’ve seen how the right data infrastructure accelerates medical breakthroughs. Analyzing it quickly and securely is essential for bringing treatments to market safely and efficiently. However, these results are meaningless if they don’t reach patients. Combination therapies will allow for personalized medicine, using a person’s unique profile to predict the best treatment. About the American Diabetes AssociationThe American Diabetes Association (ADA) is the nation’s leading voluntary health organization fighting to end diabetes and helping people thrive. Thousands of leading physicians, scientists, and health care professionals from around the world are expected to convene both in person and virtually to unveil cutting-edge research, treatment recommendations, and advances toward a cure for diabetes. The next phase of research will focus on conducting clinical trials to evaluate its performance in real-world settings. Linong Ji, a co-author and a diabetes researcher at Peking University People’s Hospital in Beijing, says ecnoglutide also improved risk factors for heart disease and diabetes, and reduced the amount of fat in people’s livers. The SUMMIT trial also showed similar outcomes by reducing the risk of cardiovascular death, heart failure exacerbation and improving functional capacity of patients . In the SUSTAIN 6 , PIONEER 6 , and the LEADER clinical trials, studying the effects of GLP-1 in patients with DM2, there has been evidence of slowing of CKD progression by lower rates of eGFR reduction in the subgroup and the post hoc analyses. The trial only included adults with prior cardiovascular disease, therefore, it did not investigate primary prevention of cardiovascular disease (people with no history of a heart attack, stroke and/or peripheral artery disease). This population may now potentially benefit from semaglutide, and importantly, our results indicate the magnitude of cardiovascular risk reduction with semaglutide among people without Type 1 or Type 2 diabetes is the same as what we have seen in people with Type 2 diabetes. Both drugs mimic GLP-1’s function in the body — increasing the release of insulin and decreasing the release of glucagon, enabling better control of blood sugar as well as weight loss. These agents have now been in patients for decades without major safety signals but as with any agent, further vigilance is required. They tested thousands of different combinations of linkers, fatty acids along with changes the amino acid sequence leading to the development of semaglutide, an ultrastable receptor agonist in which a carboxylated fatty acid is coupled to lysine 26 via a hydrophilic linker (Fig. 1, Bottom panel). In the mid 1980s, John Eng was studying bioactive peptides from the venom of the Gila monster by screening for molecules with an amino-terminal histidine which he noted was shared by GLP-1 and other gut peptides. Some patients reported nausea, leading Novo to reduce the dose, but efficacy was disappointing. These new anti-obesity drugs are GLP-1 agonists, mimicking the hormone’s action by binding to GLP-1 receptors. GLP-1 agonists are a class of medications that are prescribed to manage blood sugar for those with type 2 diabetes and to treat obesity. Semaglutide was first approved by the FDA for treatment of Type 2 diabetes and, in 2021, it was approved for chronic weight management in adults with obesity. While semaglutide is the first GLP-1 being studied in large Alzheimer's trials, it is not the only drug of interest. If semaglutide proves effective, it would be the first drug originally approved for another condition to be repurposed and made widely available for Alzheimer's treatment. While originally developed for diabetes and weight management, GLP-1s may also have effects on the brain and nervous system. These drugs work by acting on the brain, so who knows what effect they might have on childhood development and beyond if young people end up taking them for the rest of their lives. And, as soon as we stop taking the drugs, our full appetite resumes and we start regaining the weight we initially lost. Semaglutide also reduced COVID-19 related deaths in patients enrolled in the STEP program .Even so, there is still limited or uncertain evidence about their long-term safety, possible side effects, and how financial ties might influence study results.Linong Ji, a co-author and a diabetes researcher at Peking University People’s Hospital in Beijing, says ecnoglutide also improved risk factors for heart disease and diabetes, and reduced the amount of fat in people’s livers.Even smaller pharmaceutical chemical firms are seeing opportunity in semaglutide.The World Health Organization (WHO) requested these reviews to help shape upcoming recommendations on using these medications for obesity treatment.In April, a meta-analysis of 26 clinical trials involving more than 160,000 people found that GLP-1 drugs significantly reduced the risk of all types of dementia. “Most of the big generics companies are looking at the semaglutide market as a very big market for themselves and are gearing up for rapid launches post patent expirations. The entry of multiple manufacturers and sellers into the market should mean lower drug prices and greater patient access. It invented a new GLP-1 mimic, semaglutide, that could be injected once a week. The drug was first approved in 2010, but the problem was that a patient had to inject it daily. Mount Sinai Hospital has received investigator-initiated grant support from Amgen, Eli Lilly Inc., Novo Nordisk, Pfizer and Zealand Pharmaceuticals Inc. to support preclinical studies in the Drucker laboratory. Using a protocol of escalating doses, a once daily injection significantly decreased HbA1c by 1.1 to 1.6% in diabetic patients and also caused significant weight loss of 5% or greater in 54% of patients, leading to its approval in 2010 (21).Larger studies, with significantly more participants living with wider ranges of PD stages, are needed before we can make the connection between GLP-1 agonists and symptom management or disease progression.Our findings expand the opportunity to treat patients who have overweight or obesity and existing heart disease without Type 1 or Type 2 diabetes, and we have a chance to significantly reduce their risk of a secondary cardiovascular event including death.”Previously hailed – or derided – as weight-loss aids for the rich and famous, drugs such as Mounjaro, Wegovy and Ozempic took on a far more expansive role in 2025.Usage across the population A nationally representative survey conducted by RAND found that 11.8% of Americans have used GLP-1 drugs for weight loss, and about 14% express interest, while 74% say they do not plan to take them.A Hong Kong-based pharmaceutical company, Ascletis, is also investigating the benefit of once-daily oral drug, called ASC30, for weight loss. The role of GLP-1 clinical trials will continue to grow as researchers refine these approaches and gather long-term safety data. This underscores that obesity is a chronic disease requiring chronic treatment. Critically, the SURMOUNT-4 trial showed that when people stopped taking tirzepatide, they regained an average of 14% of their body weight. Originally developed to improve glycemic control in type 2 diabetes, drugs like semaglutide (Ozempic/Wegovy) and tirzepatide (Mounjaro/Zepbound) have proven remarkably effective at helping patients lose weight. The BELIEVE Phase 2b trial was a randomized, double-blind, placebo-controlled, multicenter study evaluating the effects of bimagrumab, alone and in combination with semaglutide, in adults with overweight or obesity. In April, a meta-analysis of 26 clinical trials involving more than 160,000 people found that GLP-1 drugs significantly reduced the risk of all types of dementia. Weekly semaglutide also reduced the incidence cardiovascular events in overweight patients with pre-existing cardiovascular disease but without diabetes and also in obese patients without diabetes (24). For each participant, researchers assessed symptoms before treatment and after 12 months with daily injection of either placebo or lixisenatide. As part of this study, a mouse model of Parkinson's demonstrated that lixisenatide improved movement issues and preserved brain cells, suggesting GLP-1 agonists may treat the underlying causes of PD. The study showed that lixisenatide, which was approved by the FDA to help diabetics control blood sugar in 2016, helped movement symptoms in people with PD and may slow the progression of Parkinson’s. These drugs mimic the action of a natural hormone that regulates blood sugar levels. Liraglutide was the first GLP-1 agonist studied in the LIVE trial (Effect of Liraglutide on Left ventricular Function in Stable Chronic Heart Failure Patients) a randomized control trial in patients with chronic stable HFrEF with or without type II DM, but it failed to show improvement in systolic function or clinical outcomes . Longitudinal studies strongly suggest an association of obesity with heart failure with preserved ejection fraction, increasing the relative risk by up to 56 % compared to normal weight, even after correcting for other risk factors . Semaglutide appears to be the most studied with now proven positive outcomes in patients with or without diabetes and cardiovascular disease , , . Since cardiovascular complications are the most common cause of morbidity and mortality in diabetics, it became essential to study the impact of GLP-1 agonists on CV outcome in these patients. Because semaglutide is already on the market and Food and Drug Administration (FDA)-approved for other health conditions, access could potentially happen much faster than with a brand-new medication.If the data are positive, the drug's manufacturer, Novo Nordisk, may apply for regulatory approval to market semaglutide for Alzheimer's disease. Consequently, patients prescribed a GLP-1 agonist while on warfarin although no dose adjustment is required, warfarin levels via an international normalized ratio (INR) should be obtained routinely . Dose adjustments are recommended given delayed clearance in moderate renal dysfunction (especially in patients over 70 years of age). Semaglutide is currently contraindicated in patients with a personal or family history of medullary thyroid cancer or multiple endocrine neoplasia . Their collective efforts have done what few thought possible—the development of highly effective medicines for reducing weight. More research is needed to understand the differences between various GLP-1 agonists on PD symptoms. Of note, those who received lixisenatide had more gastrointestinal side effects — 46% of participants on lixisenatide had nausea and 13% experienced vomiting. Efinopegdutide achieved 11.8% weight loss and significantly reduced liver fat by 72.7% in people with fatty liver disease. Retatrutide’s 24.2% was in people with obesity but without diabetes, while Orforglipron’s 14.7% was achieved in people with both conditions—a harder clinical challenge. For example, a 72-week trial provides more meaningful data on long-term weight maintenance than a 24-week study. More detailed studies showed that people were seeing benefits to their health independent of how much weight they lost. But far from stopping there, evidence that these drugs could transform almost every corner of medicine truly exploded this year. This section collects any data citations, data availability statements, or supplementary materials included in this article. These include a dual agonist combining glucagon and GLP-1 activity and another with GIP and GLP-1 activity. 17,604 patients with preexisting cardiovascular disease (CVD) but no history of diabetes were enrolled and randomized to receive either 2.4 mg of Semaglutide or a placebo weekly. Therefore, it was logical to study the impact of GLP-1 agonists in patients with known or at risk for atherosclerotic coronary artery disease. In this article, we present an in-depth review of the literature on the newly discovered role of this class of drugs in mitigating CV risk and treatment of CV disease. Semaglutide, a GLP-1 receptor agonist, has emerged as a promising agent in cardiovascular disease management, particularly for patients with obesity and diabetes. In addition, 28% of the study participants were female, which is not proportionate to the number of women with cardiovascular disease and overweight or obesity in the general population. Update: New Study Finds Drugs like Ozempic Ineffective for Parkinson’s Treatment While current GLP-1 drugs have transformed treatment for many, side effects remain a challenge. In the case of the GLP-1 drugs, the weight loss caused by the initial drop in appetite is undercut by an apparent exponential increase in caloric intake as our body ratchets up our hunger again. Weight loss tends to plateau because the same amount of effort to cut calories—whether through willpower, drugs, or surgery—is met with growing resistance as ongoing weight loss increasingly activates our feedback control circuit, stimulating our appetite. Commissioned by the World Health Organization, the reviews will contribute to upcoming WHO guidelines on the use of GLP-1 receptor agonists for treating obesity. Because body composition, eating patterns, and health behaviors differ around the world, the authors emphasized the need to understand how these drugs work in more diverse populations. Most of the studies included in the reviews were funded by the companies that manufacture the drugs and were shaped by those companies in terms of design, analysis, and reporting. Even so, there is still limited or uncertain evidence about their long-term safety, possible side effects, and how financial ties might influence study results. This is concerning since obesity contributes directly to the risk for developing cardiovascular disease and premature cardiovascular death, as noted in the Association’s 2021 scientific statement on obesity and cardiovascular disease. No one involved in the study — not the participants, the health care professionals or trial investigators — knew which participants were receiving semaglutide or placebo. Study participants were randomly assigned to take either 2.4 milligrams of semaglutide (the FDA-approved semaglutide dose for weight management) or a placebo once a week, which is higher than the FDA-approved semaglutide dose limit for Type 2 diabetes of 2.0 mg/week. A phase II trial began enrolling US participants with obesity in March to test it against a placebo and tirzepatide — sold as Mounjaro and Zepbound by Eli Lilly. At the maximum dose of 2.4 milligrams, 92.8% of people lost at least 5% of their body weight, compared with 14% of people receiving placebo injections. At first, Chinese pharmaceutical companies rushed to make similar versions of blockbuster weight-loss drugs, such as Wegovy and Ozempic, that have taken the world by storm. Studies looking into medications with dual biologic pathways like Tirzepatide, which have co-agonist action on (GLP1 and GIP glucagon insulinotropic polypeptide) receptors have been shown to be more effective in diabetic, weight loss and lipid control (SURPASS-2 Trial) , the effect on weight loss. In conclusion, though GLP-1 analogs were primarily considered as anti-diabetic medications, recent evidence suggests their beneficial role in patients at high risk for cardiovascular events, including for primary prevention. The lixisenatide group showed better movement symptoms compared to the control group after two months, suggesting that lixisenatide may have a positive impact on disease progression. The participants were diagnosed with Parkinson’s within the prior three years and were taking dopaminergic medications, such as levodopa, and continued to do so through the trial. However, compared with liraglutide and semaglutide (such as Wegovy), lixisenatide appears to be more effective in crossing the blood brain barrier. Parkinson's disease is a neurodegenerative disorder where dopamine-producing cells in the brain slowly break down over time. GLP-1s beyond weight loss as multi-system therapies Providers should prepare for a rapidly evolving landscape and educate patients about upcoming options.¹ Clinical trials enrol carefully selected participants, provide intensive coaching and deliver high medication doses. Despite these improvements, persistence declines sharply over longer durations, with only 14% of patients remaining on Wegovy after three years. Despite this progress, only 14% of patients remain on Wegovy after three years (Figure 3).7 Real-world analyses show that half of patients discontinue within a year.5,6 However, persistence appears to be improving. The participants were diagnosed with Parkinson’s within the prior three years and were taking dopaminergic medications, such as levodopa, and continued to do so through the trial.Together, the work of these five scientists has launched a new class of medications and, with them, a new field of research to understand their therapeutic effects beyond obesity and diabetes.Dropout rates were 6-11% due to side effects, versus 5% on placebo, meaning about 90% of people continued treatment.Sitagliptin was approved in 2006, but in contrast to the GLP-1 agonists, DPP4 inhibitors have little or no effect on body weight.Studies that recruit participants in China are also important for investigating the efficacy of GLP-1 drugs in Asian populations, which could reveal differences not observed in studies from Europe or the United States.Instead of most of it being cleared from the body within two and a half minutes, like native, natural GLP-1, much of the drug remains in the body for two and a half hours. The researchers also performed pre- and post-study CT brain scans on select participants, finding that Exenatide did not impact dopamine activity in the PD-relevant regions of the brain. The company has applied for permission from the US Food and Drug Administration to run a phase II trial. “Obesity and diabetes are major problems in Asian populations in China and in India,” he says. Bofanglutide, developed by Gan & Lee Pharmaceuticals in Beijing, is another biweekly injectable treatment, but it targets only GLP-1. Arias says the willingness of both companies to lower prices for self-paying patients shows high demand for these drugs even among people without insurance coverage. Some biotech companies want to develop weight-loss drugs that, unlike semaglutide and tirzepatide, preserve muscle mass. Releasing insulin and suppressing glucagon help control blood sugar levels in people with type 2 diabetes. At least 10 generics firms have approached India’s drug regulator for permission to conduct human clinical trials on semaglutide, according to a report by Arias and his team at Iqvia. Both liraglutide and semaglutide are 31-amino-acid-long peptides. A The World Health Organization and the World Obesity Federation use the term obesity to describe having a body mass index (BMI) of 30 kg/m2 or greater. More than 1 billion people in the world have a body mass index (BMI) ≥30 kg/m2. The company hopes to capture a large share of India’s semaglutide market, which Lupin chief financial officer Ramesh Swaminathan said in an interview with CNBC could be worth $1 billion per year. A recent clinical trial, published in the New England Journal of Medicine, tested whether a GLP-1 agonist called lixisenatide could be a new treatment approach for people in the early stages of Parkinson's.Comparing the impressive weight loss numbers from GLP-1 clinical trials requires context.One of the most promising innovations in obesity management is the integration of digital coaching with flexible medication dosing.We help pharmaceutical organizations analyze trial data across secure, distributed environments without compromising patient privacy.Within 12 months, this resistance, combined with the decreased caloric needs from being lighter, matches the persistent effort to cut calories, and weight loss plateaus.The National Institute of Health-sponsored FIGHT trial (Functional Impact of GLP-1 for HF Treatment) randomly assigned 300 patients with HFrEF and recent decompensation regardless of diabetes status to liraglutide or placebo for 6 months .Both liraglutide and semaglutide are 31-amino-acid-long peptides. New Weight Loss Drugs This study had a small sample size and only assessed the drug in those who were newly diagnosed (diagnosed within three years). This study may mean that certain GLP-1 agonists could be beneficial in reducing certain Parkinson’s symptoms. After 12 months of taking lixisenatide or a placebo, participants underwent two months without any treatment, with symptoms reassessed. While the movement symptoms of the lixisenatide group did not change compared to the start of the trial, the placebo group experienced worsening of their symptoms. Whether you’re evaluating cost-effectiveness, optimizing adherence or designing a lifestyle program to accompany pharmacotherapy, the right data makes the difference. Use comprehensive, longitudinal data to understand how these medications perform in the populations you serve. If you’re a payer, employer or provider navigating the GLP-1 revolution, don’t rely solely on published trials. Real-world evidence is essential for guiding coverage decisions, tailoring treatment protocols and maximizing patient outcomes. A section reserved for HealthVerity Marketplace data illustrates the richness of real-world evidence available to inform strategic decisions. This post digs deep into the latest real-world data, safety signals and market dynamics shaping GLP-1 therapies. Insurance-grade solutions that excel in managing risk and rebates To learn more about how we are advocating for everyone affected by diabetes, visit us on X (@AmDiabetesAssn). This February, a new study published in the medical journal The Lancet has cast substantial doubt on the potential effectiveness of the diabetes drug class GLP-1 receptor agonists on treating Parkinson’s disease (PD).Early studies suggested that intravenous GLP-1 agonists may improve left ventricular function, myocardial oxygen uptake, and physical performance in congestive heart failure .Thousands of leading physicians, scientists, and health care professionals from around the world are expected to convene both in person and virtually to unveil cutting-edge research, treatment recommendations, and advances toward a cure for diabetes.The results demonstrated the combination of bimagrumab and semaglutide therapy led to greater reductions in weight, body fat, visceral fat, and markers of inflammation compared to either treatment alone.17,604 patients with preexisting cardiovascular disease (CVD) but no history of diabetes were enrolled and randomized to receive either 2.4 mg of Semaglutide or a placebo weekly.In the mid 1980s, John Eng was studying bioactive peptides from the venom of the Gila monster by screening for molecules with an amino-terminal histidine which he noted was shared by GLP-1 and other gut peptides. Dozens of GLP-1 drugs are being developed and tested in China, with “many more to come”, says Drucker. People receiving ecnoglutide were also able to maintain their reduced weight after stopping treatment, regaining around 1% of their body weight over a 7-week period. These drugs mimic the hormone GLP-1, which is involved in regulating appetite and managing blood-sugar levels. Study Results These multi-agonist therapies target GLP-1, GIP (Glucose-dependent Insulinotropic Polypeptide), and glucagon receptors. Obesity treatment is evolving beyond the single-hormone approach. If approved, orforglipron could be the first widely available oral GLP-1 for obesity. Additionally, orforglipron reduced the inflammation marker high-sensitivity C-reactive protein by 50.6%, suggesting cardiovascular benefits. This daily pill led to an average loss of 22.9 pounds (10.5% of their body weight) over 72 weeks. Such a hormone could provide a novel treatment for diabetes and so the search for an incretin began. The 2024 Lasker~DeBakey Clinical Medical Research Award has been given to Joel Habener and Svetlana Mojsov for their discovery of a new hormone GLP-1(7-37) and to Lotte Knudsen for her role in developing sustained acting versions of this hormone as a treatment for obesity. People with Parkinson’s who also have diabetes and obesity should talk to their doctor before starting a GLP-1 agonist. Larger studies, with significantly more participants living with wider ranges of PD stages, are needed before we can make the connection between GLP-1 agonists and symptom management or disease progression. The ESSENCE trial which is an ongoing trial has shown that Semaglutide reduces the levels of alanine aminotransferase and inflammatory markers. In a meta-analysis, there was a decrease in major CV events in patients with DM2, and it was in patients with CKD with eGFR48]. There is an assumed CV benefit in CKD due to its mechanistic effect on lowering blood pressure, better blood glucose control, and weight management 11,24. In one cohort of 27,000 patients with DM2 and advanced CKD, GLP-1 has been shown to decrease all causes of mortality . Impressively, these participants had both obesity and type 2 diabetes, making weight loss more challenging. Notably, about one in four of these patients did not carry a type 2 diabetes diagnosis, suggesting that a substantial portion of GLP-1 use is being driven by weight loss and other emerging indications outside of diabetes care (Figure 2). By linking privacy-protected pharmacy records, HealthVerity Marketplace includes prescription data on more than 19.1 million patients taking GLP-1 drugs such as Ozempic, semaglutide, and Rybelsus. “GLP-1 medications have transformed the treatment of diabetes and obesity, but they can also increase the risk of muscle loss,” said Rebecca Gottlieb, Ph.D, Vice President of Advanced Sensor Technologies at Biolinq and lead author of the study. However, nausea and digestive discomfort appeared more often among people taking GLP-1 drugs, and some participants discontinued treatment because of these side effects. Semaglutide is now well known as the active ingredient in Novo Nordisk’s blockbuster type 2 diabetes drug Ozempic and weight-loss drug Wegovy, which were approved by the US Food and Drug Administration in 2017 and 2021, respectively. In the mid-2000s, Novo Nordisk had developed a peptide called liraglutide that mimics the gut hormone glucagon-like peptide-1 (GLP-1), leading to antidiabetic effects and weight loss. The success of these medicines has spurred development of next-generation GLP-1-based drugs, promising greater weight loss, improved tolerability and additional options for the route and frequency of dosing. While most drugs activate the GIP receptor, AMG133 blocks it while activating GLP-1, showing 14.5% weight loss by day 85. This hormone, which helps control appetite, is being combined with semaglutide in a drug called cagrisema to boost weight loss. All of the data presented in the figures, as well as standard errors, confidence intervals, and sample sizes, can be found in the appendix. Readers should keep in mind that the data presented here are self-reported; therefore, they may not comport with other possible estimates based on diagnoses from health care professionals or on prescription data. Additionally, we highlight age and sex differences, key demographic dimensions not fully explored in the KFF study. Our more-recent survey data allow us to examine whether GLP-1 use rates have changed since 2023. Ecnoglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist analogue, similar to the blockbuster obesity drug semaglutide. Results from a phase III trial of ecnoglutide show that people receiving a weekly injection of the drug lost up to 13.8 kilograms over 48 weeks of treatment. This could lead to a paradigm shift where cardiovascular risk management in obese patients might increasingly include pharmacological strategies aimed at weight reduction and metabolic regulation rather than focusing solely on traditional risk factors such as dyslipidemia and hypertension. Costs remain a major barrier, particularly for semaglutide and tirzepatide, while liraglutide has become more affordable since its patent expired. What is clear, says Goldstone, is that even with the need for larger, longer trials, “we’re going in the right direction”. In the past year, treatments such as Wegovy, Mounjaro and Zepbound have become household names. But there are many questions left to answer, not least what the future holds for weight-loss medications and society at large Early animal studies suggested that Liraglutide and Semaglutide reduce the development of atherosclerotic plaques in mice models, even at doses that did not lead to weight loss or substantial cholesterol lowering . Interestingly, in the SELECT trial 24 % of patients (4286 patients) had an investigator reported diagnosis of HF at baseline (31 % HFrEF, 53 % HFpEF, and 16 % were unclassified) . This finding may indicate that the effect of Semaglutide on heart failure goes beyond weight. Albiglutide was also tested in 82 patients with type II DM with HF and LVEF 22]. In a small pilot study in both diabetic and non-diabetic patients, 72 h of intravenous GLP-1 infusion administered to patients with acute myocardial ischemia undergoing percutaneous revascularization improved left ventricular ejection fraction and regional wall motion . It is also FDA-approved for weight loss in people with obesity. The drugs have also emerged as a powerful treatment for obesity, which can take a devastating long-term toll on multiple organs and organ systems. In recent years, GLP-1 therapies have become a highly effective treatment for type 2 diabetes, which affects around 35 million people in the United States and more than 460 million worldwide. In the 1990s, Knudsen and her team at Novo Nordisk used these insights about the biology of GLP-1 to develop GLP-1 therapies for type 2 diabetes and obesity — namely liraglutide, and later, semaglutide, which is more stable and longer acting. As a result, payers and guideline bodies are considering broader coverage for patients at high cardiovascular risk. In a separate analysis between 2020 and 2023, one HealthVerity closed claims dataset had more than 1.5 million patients who had at least one prescription for tirzepatide or semaglutide. This provides a clear view into how these therapies are being integrated into diabetes care at scale and highlights the value of Marketplace data for tracking treatment adoption and patient outcomes in real time (Figure 1). Between early 2022 and mid-2024, more than 6 million patients were identified with a type 2 diabetes diagnosis. In China, 17 candidates have progressed to Phase 3 clinical trials or are in the premarket application stage. Structurally unique GLP-1-based medicines that achieve substantially greater and rapid weight loss may impact musculoskeletal health, providing a rationale for therapeutics that more selectively target adipose tissue loss while preserving muscle mass and strength. The future of obesity treatment is being written now. We help pharmaceutical organizations analyze trial data across secure, distributed environments without compromising patient privacy. Tables 1–3 provide data used in the corresponding figures in this report. The majority of those who reported having side effects noted that they are mild and not serious. Additionally, about one-fifth of adults who use GLP-1 agonists reported having experienced vomiting. Figure 3 shows the overall prevalence of these side effects among our survey sample, with distinctions made as to whether the side effect was mild or severe. Among those 65 and older, use of GLP-1 agonists is somewhat higher for men than for women. This study may mean that certain GLP-1 agonists could be beneficial in reducing certain Parkinson’s symptoms.In the case of the GLP-1 drugs, the weight loss caused by the initial drop in appetite is undercut by an apparent exponential increase in caloric intake as our body ratchets up our hunger again.Given these positive results with the SUSTAIN-6 trial, the SELECT trial evaluated the impact of Semaglutide on Cardiovascular outcomes in Obese non-diabetic patients .But far from stopping there, evidence that these drugs could transform almost every corner of medicine truly exploded this year.GLP-1s are no longer just “weight-loss drugs”; they may soon be used to treat liver disease, cardiovascular conditions, sleep apnea and even reduce cancer risk.2Imagine managing weight and blood sugar with a daily pill—no injection anxiety, refrigeration, or disposal concerns.Combination therapies will allow for personalized medicine, using a person’s unique profile to predict the best treatment. Shenzhen Readline Biotech, a Chinese peptide manufacturer, now makes semaglutide and tirzepatide for companies that want the molecules for R&D, but the company is prepared to sell bulk quantities of semaglutide in the coming months. Even smaller pharmaceutical chemical firms are seeing opportunity in semaglutide. For instance, Bachem, a leader in peptide manufacturing, is expanding its production capabilities amid rising demand for peptides, including semaglutide. And companies such as Brazil’s Biomm, which plans to sell the drug but doesn’t have in-house manufacturing capabilities, are forging deals with other manufacturers. However, muscle mass does not appear to recover when the drug is stopped and is of potential concern especially for older patients though its impact on overall health is unclear (1). The potential benefit of semaglutide in other clinical settings is being actively explored. Sitagliptin was approved in 2006, but in contrast to the GLP-1 agonists, DPP4 inhibitors have little or no effect on body weight. Other companies began developing drugs that inhibit DPP-4, the enzyme that degrades GLP-1(7-37). Interestingly, in a subgroup analysis of the STEP-HFpEF program, patients with atrial fibrillation (Afib) showed improvement in heart failure related symptoms compared to patients without Afib . The effect of Semaglutide on the symptomatology of heart failure among male and females was similar despite females having more weight loss (9.6 % compared to males with 7.2 %) . STEP-HFpEF trial studied 529 patients with HFpEF, NYHA II-IV symptoms, and BMI of 30 or higher who were randomized to once weekly Semaglutide vs placebo for 52 weeks . Recent studies have demonstrated significant benefits of Semaglutide beyond glycemic control, including reduced major adverse cardiovascular events (MACE), improvements in heart failure symptoms, and weight reduction. Additionally, the Food and Drug Administration (FDA) urges caution regarding compounding (i.e. mixing of several medications to create a customized drug) of Semaglutide formulations since they are not assessed for efficacy, safety, or quality 62,63. However, this warning is not unique to Semaglutide among the drug class . Although the association with thyroid and pancreatic cancer is not fully established, both formulations of Semaglutide have received an official black box warning for thyroid C-cell tumors in the United States based on data from rodent studies . The safety profile for Semaglutide is like that of other GLP-1 receptor agonists . Adverse events investigated and reported ranged from gastrointestinal side effects, pancreatic safety (pancreatitis and pancreatic cancer), gallbladder events, acute renal injury, diabetic retinopathy, and thyroid cancer 19,, , . Wegovy has shown promise in improving MASH.¹ If confirmed in larger trials, GLP1 drugs could become a cornerstone of liver disease management. "We need more data on the long-term effects and other outcomes related to cardiovascular health, particularly in lower-risk individuals," says Eva Madrid, co-lead researcher from the Universidad de Valparaíso, Chile. "These drugs have the potential to bring about substantial weight loss, particularly in the first year," says Juan Franco, co-lead researcher from Heinrich Heine University Düsseldorf, Germany. The reviews found little to no difference between the drugs and placebo when looking at major cardiovascular events, mortality, or quality of life. Glucagon-like peptide-1 (GLP-1) receptor agonists were first introduced in the mid-2000s to help people with type 2 diabetes. Understanding the complications of obesity shows why this shift is so important. Scientists are also exploring completely new pathways like Growth Differentiation Factor 15 (GDF-15) agonists. Interestingly, GIPR antagonists offer a different approach. Researchers are pushing beyond single-target approaches, combining hormones and exploring new pathways to broaden treatment effectiveness. The bottom line is that the safety profiles are manageable for most people with proper medical supervision. Ozempic, which contains the GLP-1 drug semaglutide, was initially considered a treatment for type 2 diabetes only Ozempic, which contains the GLP-1 drug semaglutide, was initially considered a treatment for type 2 diabetes onlyAlamy Stock Photo Phase 2 data of retatrutide, a similar triple agonist developed by Eli Lilly, has shown a remarkable 24% weight loss after 48 wk of treatment, without reaching a plateau (1). While semaglutide thus far appears to be quite safe, the nausea that it causes is clinically significant, leading many patients to discontinue treatment (1). In diabetic patients, semaglutide significantly reduced the incidence of cardiovascular events by 26% vs. placebo (23). In addition to taking either semaglutide or placebo for the trial, all participants also received standard of care treatment for cardiovascular disease, such as cholesterol modifying medications, antiplatelet therapies, beta blockers or other treatments. Notably, their work contributed to the development of GLP-1 drugs, which have revolutionized treatment for type 2 diabetes and obesity. Their research, and the therapies enabled by it, have profoundly reshaped the treatment of type 2 diabetes and obesity and have shown promise for other cardiometabolic conditions, such as heart failure, chronic kidney disease, and fatty liver disease. The same study showed that patients taking higher doses and remaining adherent achieved weight loss comparable to clinical trials.5 The meeting, Nov. 11-13, in Philadelphia, is a premier global exchange of the latest scientific advancements, research and evidence-based clinical practice updates in cardiovascular science. Semaglutide is a GLP-1 medication primarily prescribed for people with Type 2 diabetes. The therapies are now being studied for other cardiometabolic conditions, including heart failure, chronic kidney disorders, and fatty liver disease. Simultaneously, Habener was studying the interaction between glucagon and somatostatin, another hormone made by the pancreas that inhibits the release of insulin and glucagon. The 2025 Breakthrough Prize in Life Sciences has been awarded to five scientists for the discovery and characterization of the hormone glucagon-like peptide-1, or GLP-1 — findings that subsequently led to the development of treatments based on GLP-1. In another study, GLP-1R was expressed less in CKD mice and correlated with the disease severity . The findings of the SELECT trial have several important implications for clinical practice. This was a large-scale, multicenter, double-blind, randomized, placebo-controlled study. Meanwhile, leading firms in China, such as Jiangsu Hengrui Pharmaceuticals, and in Europe, notably Sandoz, have also announced plans to market generic semaglutide. Among Indian companies, Dr. Reddy’s Laboratories has already received permission from regulators to market generic semaglutide. Novo Nordisk deploys a recombinant yeast-based fermentation method to produce the backbone of liraglutide and semaglutide, followed by solid-phase synthesis to make certain additions and modifications to the backbone. On the other hand, GLP-1 effects on vascular endothelium result in vasodilation and modulation of atherosclerosis via anti-inflammatory pathways 5,6. Their primary biological impact on the pancreas is to secrete insulin, reduce glucagon, and induce early satiety by delaying gastric emptying and acting on hypothalamic receptors. The cardiovascular (CV) community has generated significant enthusiasm for its potential cardiovascular benefits. Help make sure the Association can continue to provide critical information and programs to people facing Alzheimer's today and tomorrow. The time between a promising trial announcement and final regulatory decisions can be filled with both hope and uncertainty. Wegovy, the high-dose Ozempic used for weight loss, costs up to $1,350 a month, which, again, may have to be paid in perpetuity since any lost weight can pile back on if you stop taking it. Within 12 months, this resistance, combined with the decreased caloric needs from being lighter, matches the persistent effort to cut calories, and weight loss plateaus. In a way, GLP-1 agonist drugs work like birth control pills. Higher efficacy often comes with predictable side effects. These results come from different patient populations and trial lengths. Each trial is unique, with different patient populations, durations, and endpoints, making direct comparisons tricky. Those who continued treatment lost an additional 5.5%. Treated patients lost an average of 12.4% of their initial body weight compared to individuals who received placebo (1). This resulted in an average of ~5 kg weight loss with the majority of patients losing more than 5% of their weight (1). Further, despite internal resistance at Novo, Knudsen initiated trials administering a higher dose of liraglutide (Saxenda) for the treatment of obesity. Using a protocol of escalating doses, a once daily injection significantly decreased HbA1c by 1.1 to 1.6% in diabetic patients and also caused significant weight loss of 5% or greater in 54% of patients, leading to its approval in 2010 (21). From the outset, Knudsen believed that this would not only become a treatment for diabetes but one for obesity. By linking pharmacy claims, electronic medical records, social determinants and lab results, we can uncover patterns in adherence, dosing and comorbidities that clinical trials can’t reveal. While early data show improved persistence, only a minority of patients remain on therapy beyond two years.6 Payers must balance high upfront costs against potential long-term savings from reduced complications. The improvement may reflect easing drug shortages, expanded insurance coverage and better management of side effects. A recent analysis of pharmacy claims found that 63% of patients starting Wegovy or Zepbound in early 2024 were still taking the drug one year later.7 This is up from 40% among patients who started in 2023. About a third of participants (28 people) receiving lixisenatide opted for a lower dose during the study due to side effects. After 12 months of treatment, people who received lixisenatide showed better results with their movement symptoms compared to those who received a placebo. As scientists learn more about the GLP-1 biological pathway and how it affects dopaminergic neuron health, there will likely be future development and trials of new GLP-1 drugs specifically designed for Parkinson’s. These results suggest that the current GLP-1 receptor agonists medications are not effective as Parkinson’s disease-modifying treatments. A Hong Kong-based pharmaceutical company, Ascletis, is also investigating the benefit of once-daily oral drug, called ASC30, for weight loss. Attendees will receive exclusive access to thousands of original research presentations and take part in provocative and engaging exchanges with leading diabetes experts. About the ADA’s Scientific SessionsThe ADA's 85th Scientific Sessions, the world's largest scientific meeting focused on diabetes research, prevention, and care, will be held in Chicago, IL on June 20-23. “While patients are advised to consume more protein to preserve muscle, it’s often difficult to know if they’re getting enough. A new study, presented as a late-breaking poster, demonstrates proof of concept for a continuous protein sensor as a tool to prevent muscle loss during GLP-1 therapy. “Ozempic face” is a term used to describe a distorted facial appearance among users of the drug. Rare but serious adverse effects are also emerging. The most common side effects include nausea, vomiting, diarrhea, and constipation. Even though they continued to get injected every week for three more years, they didn’t lose any more weight over the subsequent 143 weeks. Ozempic was approved in 2017 to treat diabetes. Orforglipron isn’t the only oral player in GLP-1 clinical trials.Rare but serious adverse effects are also emerging.Researchers are pushing beyond single-target approaches, combining hormones and exploring new pathways to broaden treatment effectiveness.Many people with type 2 diabetes still do not meet treatment goals, driving the need for new therapies.However, it was not clear whether the hormone would provide a clinical benefit in diabetic patients.Between early 2022 and mid-2024, more than 6 million patients were identified with a type 2 diabetes diagnosis.Interestingly, GIPR antagonists offer a different approach. This is a complete paradigm shift in treating obesity as a chronic disease. The convenience of a daily pill like orforglipron, which delivered 10.5% weight loss, represents a massive leap in patient accessibility. For millions struggling with obesity and related conditions, these breakthrough treatments are life-changing. We’ve shifted from surgery or marginal results to oral medications delivering up to 24.2% weight loss, rivaling invasive procedures. Visit HealthVerity Marketplace to access robust, real-world data on GLP-1 therapies and other high-impact drugs. In a recent observational study, individuals who discontinued semaglutide or tirzepatide within the first three months lost only 3.6% of their body weight, while those who quit between three and twelve months lost 6.8%. For patients who stop treatment early, weight regain is common. The “treat-to-target” strategy allowed patients to start low and increase the dose only when weight loss stalled. A Danish cohort study evaluated an online weight-loss program that combined behavioral support with individualized semaglutide dosing. In its 48-week Phase 2 trial, participants with obesity achieved a mean weight reduction of 24.2% at the highest dose. Its safety profile is similar to other GLP-1 drugs, with GI side effects (nausea, vomiting, diarrhea) being the main concern. Small-molecule drug innovation has created new nonpeptide agonists that survive digestion and are absorbed when swallowed, opening treatment to millions. My experience building precision medicine tools gives me unique insight into how these breakthrough trials are reshaping obesity treatment. Weight control strategies like bariatric surgeries have significantly reduced heart failure prevalence per registry studies . Liraglutide, Dulaglutide, and Semaglutide are the 3 GLP-1 agonists approved for once-weekly use. Exenatide, a synthetic GLP-1 analog, was the first GLP-1 analog approved by the FDA in 2005 for clinical use in diabetics, as a once-daily subcutaneous injection 7,8. The Ozempic era is only just beginningIn the past year, treatments such as Wegovy, Mounjaro and Zepbound have become household names. The cardiovascular benefits observed in the SELECT trial were concomitant with its known metabolic effects, including significant reductions in body weight and waist circumference . A meta-analysis of these trials suggested that GLP-1 agonists reduce the risk of major adverse cardiovascular events (MACEs) in diabetic persons with or without established ASCVD 45,46. Given this potent effect on weight reduction, Semaglutide was studied in 2 randomized control trials for clinical outcomes in both diabetics and nondiabetics with obesity and HFpEF , , . The National Institute of Health-sponsored FIGHT trial (Functional Impact of GLP-1 for HF Treatment) randomly assigned 300 patients with HFrEF and recent decompensation regardless of diabetes status to liraglutide or placebo for 6 months . The event reduction may not be related to weight reduction as explained previously. Semaglutide also reduced COVID-19 related deaths in patients enrolled in the STEP program . The seminal STEP program evaluated the impact of Semaglutide in patients with HFpEF. The trial was neutral overall with no differences in HF-related outcomes or functional capacity. Still, insurance coverage and cost considerations mean both drugs remain relevant, and patient-centred conversations about therapy choice are critical.¹ That changed when the SURMOUNT-5 trial compared tirzepatide (the active ingredient in Zepbound) and semaglutide directly. These insights reveal how GLP-1 therapies are being used in the real world, including how much weight patients are actually losing, a topic that’s driving intense interest across healthcare and policy circles. Few areas of medicine have captured public interest over the past two years quite like glucagon-like peptide-1 (GLP-1) receptor agonists. With your support, the American Diabetes Association® can continue our lifesaving work to make breakthroughs in research and provide people with the resources they need to fight diabetes. This growing research pipeline provides hope that GLP-1s could become part of a new class of Alzheimer's treatments, potentially complementing other approaches that target amyloid and tau proteins. This process will involve careful review of safety and efficacy by the FDA and other global agencies, and decisions about how and when the drug can be prescribed. These findings could represent a pivotal moment for Alzheimer's care, shaping how the disease is treated and managed for years to come. The next generation of GLP-1 therapies promises not just to treat diseases, but to fundamentally reshape our approach to health and wellness. (Similar accounts have been made of “Ozempic butt.”) Media reports have linked the drug with facial aging, but the sagging appearance has been ascribed simply to the accelerated loss of fat in the face. My experience building precision medicine tools gives me unique insight into how these breakthrough trials are reshaping obesity treatment.Parkinson's disease is a neurodegenerative disorder where dopamine-producing cells in the brain slowly break down over time.In 2022, a modified version of the GLP-1/GIP dual agonist, tirzepatide (Zepbound®), developed by Eli Lilly induced an average weight loss of 21% in humans with obesity and 15% weight loss in obese patients with diabetes (1).We’ve shifted from surgery or marginal results to oral medications delivering up to 24.2% weight loss, rivaling invasive procedures.(Similar accounts have been made of “Ozempic butt.”) Media reports have linked the drug with facial aging, but the sagging appearance has been ascribed simply to the accelerated loss of fat in the face.The combination therapy yielded 92.8% of total weight loss from fat mass compared to semaglutide alone (71.8%) and a 22.1% decrease in bodyweight (−10.8% bimagrumab alone; −15.7% semaglutide alone).Analyzing it quickly and securely is essential for bringing treatments to market safely and efficiently.“It’s been estimated that within about ten years, over half of the world’s population will have overweight or obesity,” said Dr. Lincoff.They showed that food intake prompts the gut to release the hormone into the blood, where it enhances insulin release, suppresses glucagon, and slows stomach emptying. Findings from two groundbreaking studies highlight potential pharmacological and biosensor solutions for muscle mass preservation in patients undergoing obesity treatment therapy. The reviews highlight the need for long-term, independent investigations to guide clinical and policy decisions and to better define the role of GLP-1 receptor agonists in lasting weight management. "It's an exciting moment after decades of unsuccessful attempts to find effective treatments for people living with obesity." In the United Kingdom, they are approved for weight management when combined with a reduced calorie diet and physical activity for people with obesity or for those who are overweight with related health issues. The modified drug would need to remain active 24 h/d, be as or more potent than native GLP-1, and remain physically stable for long periods of time. This was because several studies from Ole Madsen (University of Copenhagen) had shown that transplantation of some glucagon producing tumors caused profound anorexia in animals (16). These pivotal results established the potential of this new hormone as a therapy for diabetes but there was a problem. In semaglutide (Bottom), alpha-aminoisobutyric acid (X) in semaglutide replaces alanine (A), which protects the molecule from destruction by the enzyme DPP-4, and a long, hydrophilic linker connects an 18-carbon diacid to the GLP-1 moiety. In liraglutide (Middle), glutamic acid connects the GLP-1 core to a fatty acid that contains 16 carbons; this drug is administered once a day. Unlike regulators in India and China, the FDA does not require most generic drug makers to conduct human clinical trials if they can demonstrate that the generic version is chemically equivalent to the original drug. Patent expiration for semaglutide in some of the world’s biggest markets will also be an opportunity for companies that don’t make finished drugs but instead focus on active pharmaceutical ingredients. B Estimates indicate that 90% of people with diabetes have type 2 diabetes. Demand for Novo Nordisk’s semaglutide drugs and the peptide drugs of its main competitor, Eli Lilly and Company, is tremendous. Side effects About 50% of users reported nausea and one-third reported diarrhea in RAND’s survey.4 Gastrointestinal side effects are the most common reason for discontinuation.5 One of the most promising innovations in obesity management is the integration of digital coaching with flexible medication dosing. With this unmatched coverage, pharmaceutical manufacturers and healthcare researchers can move beyond traditional claims analysis to access verified insights that illuminate real-world treatment dynamics across diverse patient populations. But 2025 saw a wave of larger, randomised trials examining the drugs’ broader effects. At first, many assumed this was a simple side effect of weight loss, obesity being a major risk factor in so many conditions. Semagutide needs to be taken continuously to be effective and treatment results in loss of both fat and muscle mass, which appears to be equivalent to that seen after weight loss by dieting (1). For example, recent studies have reported clinical benefits in patients with heart and kidney failure. Subsequently, clinical studies with Semaglutide showed substantial reduction in CRP levels compared to placebo in multiple trials , , . Therefore, based on available data, Semaglutide seems to be effective in reducing events related to HFpEF in obese patients with or without diabetes (Table 2). In a prespecified analysis, the effects of Semaglutide to reduce cardiovascular death was seen both in patients with investigator-identified HFpEF and HFrEF . Joel Habener is one of five scientists recognized for research that transformed diabetes and obesity treatment Meanwhile, Novo Nordisk has yielded to pressure from US president Donald J. Trump to bring down the price of its semaglutide-based drugs. “In case of semaglutide, patients know that they have to deal with the side effects, such as nausea, only for the hours following the weekly injections,” Verma says. But Ashwani Verma, a biopharma stock analyst at the investment firm UBS, says it is difficult to gauge how much the new drugs will eat into the semaglutide market in the coming years. Arias says the success of GLP-1 drugs is spurring newer generations of molecules that could overtake semaglutide in popularity if they make it past the FDA. “This news is very encouraging for people with overweight or obesity because no treatment specifically directed at the management of obesity and overweight in people without Type 1 or Type 2 diabetes has been tested in a randomized trial and been shown to influence cardiovascular outcomes,” said lead study author A. The success of GLP-1 clinical trials is rapidly advancing obesity treatment, with drugs now delivering bariatric surgery-level weight loss without surgery. GLP-1 clinical trials are revolutionizing how we treat obesity and diabetes, with new drugs delivering weight loss results that rival bariatric surgery. The effects of Tirzepatide on weight loss and by extension on moderate to severe sleep apnea was seen in the SURMOUNT-OSA trial with a reduction in apnea-hypopnea index by −29.3 events per hour compared to placebo leading to its FDA approval as the first drug for the treatment of sleep (Table 1, Table 2). Subsequently, it was approved for reduction of major cardiovascular events in adults with known heart disease and either obesity or overweight and in patients with diabetes and known heart disease. However, it was not clear whether the hormone would provide a clinical benefit in diabetic patients. In 1987 in a study of seven human volunteers, Bloom et al. showed that an infusion of GLP-1(7-36) increased plasma insulin and reduced plasma glucose in patients that received a glucose load but not in patients who were fasted. She found that while there was abundant glucagon in the pancreas, only larger molecular weight forms of it were seen in intestine. Mojsov was intrigued by the possibility that GLP-1 or another product of the glucagon gene might have biological effects. He decided to study the processing of the glucagon protein precursor, but instead of studying the mammalian hormone he turned his attention to fish. “While weight loss may seem part of the biological ageing story, the early evidence, along with what is known about GLP-1 biology, suggests there is an independent layer of metabolic improvements, which is converting to improved biological age,” he says. GLP-1 drugs may work by acting on several of these, he says, protecting neurons through kinase pathways, which are vital for cells’ stress response; reducing cell damage by improving insulin sensitivity; and dampening inflammation. “We don’t have many drugs for addiction, and GLP-1 drugs are already licensed for other conditions, so we know they are reasonably safe.” Researchers began to discover how GLP-1 drugs act on multiple pathways, including several tied to inflammation. Findings of study demonstrating the effectiveness of combining bimagrumab – a drug designed to combat muscle loss – with a common GLP-1 receptor agonist (RA), semaglutide, were presented during a late-breaking symposium. “We are championing research to ensure people living with obesity can have access effective treatments to reduce adiposity while maintaining muscle mass critical to their well-being, and supporting durable long-term outcomes.” “As we enter a new era of obesity treatments, it’s vital to focus not just on the amount of weight lost, but on preserving muscle mass and gaining the health benefits that result from treating obesity,” said Samar Hafida, the new Vice President of Obesity Association a division of the American Diabetes Association. For those with both obesity and type 2 diabetes, SURMOUNT-2 showed 15.7% weight loss. The SURMOUNT-1 trial delivered 22.5% weight loss over 72 weeks for people without diabetes. Oral semaglutide (high-dose) showed remarkable results in the OASIS-1 trial, where people without diabetes lost 17.4% of their body weight over 68 weeks. While current treatments can help manage many PD symptoms, they do not address what causes the disease and therefore cannot prevent its progression. The study, consisting of 194 participants followed over two years, found that daily use of Exenatide did not provide any significant improvement for Parkinson’s symptoms compared to the placebo. Studies that recruit participants in China are also important for investigating the efficacy of GLP-1 drugs in Asian populations, which could reveal differences not observed in studies from Europe or the United States. Another drug being developed in China, known as UBT251, is a triple agonist, mimicking GLP-1, glucagon and another hormone called gastric inhibitory polypeptide (GIP), which is involved in fat metabolism. “It’ll give us options and it will make personalized medicine in obesity and diabetes more accessible.” Heart rate increases seen with some multi-agonists like retatrutide are typically transient. Retatrutide saw 13% discontinuation, which is reasonable given its potent metabolic effects. Fortunately, most side effects are mild to moderate and improve over time, especially with careful dose titration. Comparing the impressive weight loss numbers from GLP-1 clinical trials requires context. Beyond weight loss, 72% of participants with prediabetes returned to normal blood sugar levels, compared to just 22% in the placebo group. For those with diabetes, the PIONEER PLUS trial showed 9.8% weight loss and A1C reductions up to 2.1%. Dropout rates were 6-11% due to side effects, versus 5% on placebo, meaning about 90% of people continued treatment. This was followed by clinical trials for the treatment of obesity using higher, escalating doses of the drug (Wegovy). Eng then began a collaboration with Amylin Pharmaceutical and in a series of clinical trials, exendin-4 injected twice daily showed highly significant efficacy in Type 2 diabetic patients with lowering of HbA1c by 0.86% and modest weight loss of 1.6 kg (1, 20). GLP-1 (Top) serves as the active agent in two long-acting drugs, liraglutide (Middle) and semaglutide (Bottom), that offer new hope to people who are obese or overweight. There is currently insufficient evidence to support the use of GLP-1 agonists like lixisenatide as a treatment for people with Parkinson’s who do not have diabetes or obesity. Many people with type 2 diabetes still do not meet treatment goals, driving the need for new therapies. Usage across the population A nationally representative survey conducted by RAND found that 11.8% of Americans have used GLP-1 drugs for weight loss, and about 14% express interest, while 74% say they do not plan to take them. Participants lost 16.7% of baseline weight over 64 weeks, matching clinical trial outcomes despite using half the typical drug dose. The SELECT trial demonstrated that GLP-1 therapy rapidly reduces heart attacks and strokes.¹ These cardiovascular benefits have long been hinted at in diabetes trials, but the magnitude observed in SELECT surprised even seasoned cardiologists. If, after clinical assessment, the patient is deemed low risk according to the above-mentioned factors, then the decision to withhold should be individualized 66,67. Regarding suspension of semaglutide in the perioperative setting, the decision on whether to withhold should be based on minimizing the risk of complications. Patients with severe renal disease should avoid taking GLP-1 agonists altogether . The ESSENCE is a two-part, phase 3 study that is ongoing to evaluate the effect of subcutaneous Semaglutide 2.4 mg in participants with biopsy proven NASH and fibrosis stages 2 or 3 with primary objective of part 1 is to demonstrate improvement in liver histology with Semaglutide compared to placebo. GLP-1s are no longer just “weight-loss drugs”; they may soon be used to treat liver disease, cardiovascular conditions, sleep apnea and even reduce cancer risk.2 In January, researchers reported that people with diabetes taking GLP-1 drugs alongside standard treatment had a lower risk of 42 conditions – including dementia and muscle pain – compared with those on the standard therapy alone. No longer just considered treatments for obesity and type 2 diabetes, Ozempic gained approval in the US for treating kidney and cardiovascular disease. We knew that GLP-1 drugs like Ozempic and Wegovy did more than just help control type 2 diabetes and aid weight loss, but the extent of that potential really came to light in 2025 In 2022, a modified version of the GLP-1/GIP dual agonist, tirzepatide (Zepbound®), developed by Eli Lilly induced an average weight loss of 21% in humans with obesity and 15% weight loss in obese patients with diabetes (1).