Latest news with #GLP1RAs
Medical News Today
4 days ago
- Health
- Medical News Today
Why do some people have better weight loss results with Ozempic or Wegovy?
Research on weight loss medications, particularly glucagon-like peptide-1 receptor agonists (GLP-1RAs), and why people experience varying results is study helped identify multiple components that may affect successful weight loss among people using researchers found that taking the medication for longer and starting on semaglutide rather than other GLP-1RA options produced more successful weight loss results.A popular group of weight loss medications is glucagon-like peptide-1 receptor agonists (GLP-1RAs), which include the likes of Ozempic and Wegovy — medications that are used to treat type 2 diabetes and obesity.A study recently published in Diabetes, Obesity and Metabolism explored weight fluctuations among participants after taking GLP-1RAs. The results suggest that factors like taking GLP-1RAs longer, having greater accumulated exposure to GLP-1RAs, using semaglutide, and not having diabetes may make it more likely for some people to experience successful weight loss from GLP-1RA impacts the effectiveness of GLP-1RAs?This research involved a total of 679 participants and was a retrospective cohort study. All participants were overweight or obese, and this was determined by body mass index (BMI). Some participants also had type 2 diabetes. All participants had at least three months' worth of follow-up and at least three noted weight measurements during the had data from participants' follow-up visits, including factors like body composition and measurements of liver and kidney function. Their data looked at treatment with seven different GLP-1RAs, including semaglutide, lixisenatide, and examined weight fluctuation among participants and divided participants into three groups: successfully losing weight, staying the same weight, or regaining weight. In their analyses, they then further classified participants as having successful or unsuccessful weight reduction. The unsuccessful category included both weight regain and staying the same did their analyses at three months, six months, and then at one year. The average age of participants was thirty-seven years old, and about 21% of participants had who had been on GLP-1RAs for longer were more likely to experience successful weight reduction at six and twelve months. At the three and six-month marks, participants who experienced successful weight reduction were also less likely to have diabetes and more likely to start their treatment on the three-month follow-up, participants in the weight regain group also had higher estimated glomerular filtration rates, which measures kidney function. This was also true when looking at just participants with prediabetes. The authors note that people with obesity can experience these higher filtration rates, which can then lead to worse kidney also observed that the group that remained stable had higher fasting plasma glucose levels than the other groups and worse beta cell function and insulin resistance than participants who successfully lost do some people lose more weight on GLP-1s?In their univariate logistic regression analysis, the researchers identified several factors that may be related to successful weight loss. These included longer time on GLP-1RA treatment, semaglutide use, lower blood sugar levels, and a higher percentage of body fat. They also observed that greater Homeostasis Model Assessment of β-Cell Function levels, which helps to measure beta cell function in the pancreas and insulin resistance, was associated with successful declines in weight. For women, having a lower skeletal muscle mass was also associated with successful weight adjusting for age, sex, and BMI, the researchers found that the longer people used GLP-1RAs, the more they lost weight successfully at all the follow-up time points. At three and six months, starting semaglutide, compared to other GLP-1RAs, was linked to successful weight men, having a body fat percentage greater than 30% was associated with successful weight reduction at three months, but this was not the case for women. At three months, not having diabetes and hemoglobin A1C levels were linked to successful weight addition to these factors, researchers also observed some non-linear associations. For example, some measurements of muscle mass and basal metabolic rate had a reversed J-shaped association with successful weight analyses also revealed that higher accumulated exposure of semaglutide or liraglutide were both associated with successful weight reduction. At three months, liraglutide and semaglutide users with successful weight reduction had higher fasting plasma glucose levels. For men on semaglutide, having a greater percentage of body fat was associated with successful weight loss at a six-month follow-up. Study limitationsThis study does have benefits and potential limitations. Paunel Vukasinov, MD, a dual board-certified Internist and Obesity Medicine Specialist with Medical Offices of Manhattan and contributor to who was not involved in the research, noted the following to Medical News Today:'This study offers helpful information about the differences in weight loss results for patients treated with GLP-1 receptor agonists (GLP-1RAs). Clinical trials have shown that GLP-1RAs work well, but this study points out the varied responses in everyday clinical settings. It also tries to find the reasons behind this variability.''However, the lack of randomization, possible confounding factors, and the single-center design do weaken the conclusions. Still, it addresses an important clinical question: why do some patients do well on GLP-1RAs while others stop losing weight or regain it? It encourages us to move toward more personalized obesity care.'— Paunel Vukasinov, MDThis study was conducted among Chinese participants receiving treatment at a single weight loss clinic. Data from other countries may be helpful in future note that only 112 participants had a follow-up assessment at the one-year mark. They also note there was a lack of record for some possible confounding factors and that they weren't able to assess how lifestyle interventions throughout the follow-up could have affected outcomes. Another limiting factor was that 'longitudinal data for body composition was not systematically collected and analyzed at the follow-ups.'Does stopping medication affect results?Treatment discontinuation did happen, which meant differences in medication looking specifically at the use of semaglutide and liraglutide in the subgroup analyses, researchers only analyzed the data from the three-month and six-month follow-ups. They were also only able to look at accumulated exposure for two types of without type 2 diabetes had more limited access to GLP-1RAs, and this could have influenced the study's results. One author also noted conflicts of Raines, DO, an osteopathic physician specializing in family medicine and American Osteopathic Association member, who was also not involved in the study, noted the following limits of this study to Medical News Today:'It's important to note the limitations, namely, the small sample size and the even smaller number of participants who continued through the full 12-month follow-up period…This paper does not explore the effects of discontinuation, a crucial aspect given evidence showing significant weight regain in many individuals once GLP-1RAs are stopped, even with continued lifestyle modifications. Nor does it include tirzepatide, which, while not solely a GLP-1RA, currently shows even more promising data for weight loss than semaglutide in existing trials.'More research is required to examine some of the components of the study, such as the differences in weight loss for people with diabetes compared to those without diabetes. More research on how kidney function plays into everything may also be loss may need a personalized approachThe authors of this study suggest that data from this study could help make the use of GLP-1RAs more might help improve the success related to these medications. Kais Rona, MD, a bariatric surgeon of MemorialCare Surgical Weight Loss Center at Orange Coast Medical Center in Fountain Valley, CA, who was also not involved in the study, noted the following:'Ultimately, this study supports a personalized approach to the use of GLP-1RA medications. One that identifies important physiologic markers prior to the initiation of the treatment regimen, monitors patient response over time, and focuses on long-term success.'The research also highlights the importance of careful clinical oversight when people use GLP-1RAs. 'Many patients are currently receiving these medications from providers outside their primary care home, often without comprehensive management or long-term planning. This raises concerns about suboptimal outcomes and unintended side effects…What we now need are more long-term studies, particularly focused on sustained outcomes, strategies for maintenance after discontinuation, and optimizing individualized care,' Raines said.
Medscape
7 days ago
- Health
- Medscape
Can Orforglipron ACHIEVE the Unattainable?
First reports from the ACHIEVE-1 randomized controlled trial were presented during the American Diabetes Association 85th Scientific Sessions in Chicago and simultaneously published in The New England Journal of Medicine. ACHIEVE-1 explored the efficacy and safety of orforglipron in early T2D. As a general practitioner with a role in treating diabetes, I have been delighted to witness the evolution of the GLP-1 receptor agonists (RAs) such as orforglipron. This journey began with the discovery of exendin-4 in the mid-1990s in the venom of the Gila monster. Exendin-4 is structurally like human GLP-1 and stimulates insulin production in the body. This finding led to the development of twice-daily injectable exenatide and its approval in 2005. It also enabled the development of injectable human GLP-1 analogs such as liraglutide, dulaglutide, and semaglutide. I was an early advocate of GLP-1 RAs, given their potent glucose-lowering efficacy, secondary benefits of significant weight reduction, and low associated risk for hypoglycemia (if not used alongside sulfonylureas or insulin). During 2016, the LEADER study, the first cardiovascular outcomes trial (CVOT) of a GLP-1 RA, was published. It demonstrated a significant reduction in major adverse cardiovascular events (MACE) with liraglutide. Significant reductions in MACE were also subsequently demonstrated with semaglutide during 2016 (SUSTAIN-6 CVOT) and with dulaglutide during 2019 (REWIND CVOT). These studies drove a change in guidelines globally and positioned these GLP-1 RAs as preferred therapeutic options for patients with type 2 diabetes (T2D) and comorbid atherosclerotic cardiovascular disease (ASCVD). During 2019, oral semaglutide was approved by the FDA as the first (and still only) commercially available oral GLP-1 RA to improve glycemic control in adults with T2D. Notably, the manufacture of oral semaglutide is an expensive, complex, and technically demanding process, since it must prevent the degradation of semaglutide within the acidic gastric environment. During March 2025, the SOUL CVOT (also presented at ADA 2025) demonstrated a significant reduction in MACE with oral semaglutide in patients with T2D, ASCVD, or chronic kidney disease. Again, I was an early adopter of oral semaglutide, and it has been great for my patients with T2D to have the option of taking a noninjectable GLP-1 RA. But it is not without its drawbacks: Oral semaglutide must be taken on an empty stomach at least 30 min before any other food, drink, or medication and with no more than 120 mL of water to maximize absorption and bioavailability. These requirements made it challenging for many of my patients to fit it into their work-life schedules. A role for GLP-1 RAs in weight loss has emerged alongside their role in T2D. During 2014, liraglutide 3 mg was approved for weight management based on the SCALE studies. During 2021, semaglutide 2.4 mg was similarly approved for weight management, based on the STEP trial program. In 2023, the SELECT trial became the first GLP-1 RA CVOT (using semaglutide 2.4 mg) to demonstrate a significant reduction in MACE in patients with preexisting CVD and overweight or obesity but without T2D. This trial led to a new CV indication to be added to the semaglutide label during 2024. Finally, since 2022, once-weekly injectable tirzepatide (a dual GLP1-glucose-dependent insulinotropic polypeptide RA) has been available as a therapeutic option for patients with overweight and obesity with and without T2D, based on the SURPASS and SURMOUNT trials. Over the past 18 months, we have seen a slew of comorbidity trials published for injectable semaglutide 2.4 mg and tirzepatide, demonstrating improvements in comorbidities including heart failure with preserved ejection fraction, obstructive sleep apnea, and metabolic dysfunction associated steatotic liver disease. Orforglipron is a small-molecule, nonpeptide oral GLP-1 RA and the next stage in the evolution of the GLP-1 RA class. Nonpeptide GLP-1 RAs have the potential to provide higher oral bioavailability with no food or water restrictions and therefore simpler administration. Nonpeptide GLP-1 RAs also have a simple manufacturing process. Notably, during April 2025, Pfizer discontinued development of danuglipron (another oral, small-molecule GLP1 RA) because of concerns regarding liver toxicity. ACHIEVE recruited 559 patients with T2D who were treated only with diet and exercise or had been off other oral or injectable glucose-lowering medications for at least 3 months. Participants were randomly assigned to one of three doses of orforglipron (3 mg, 12 mg, or 36 mg) or placebo for 40 weeks. Mean duration of T2D was 4.4 years, mean HbA1c at baseline was 8%, and mean body weight at baseline was 90.2 kg. About 48% of the participants were women, and 38.3% had previously received a glucose-lowering agent (most commonly metformin). The primary endpoint was change in HbA1c at week 40. A key secondary endpoint was percent change in body weight at week 40. Orforglipron was associated with significant, dose-dependent, and clinically meaningful reductions in HbA1c (-1.24%, -1.47%, and -1.48% for the 3, 12, and 36 mg doses, respectively) compared with placebo (-0.41%). Mean HbA1c at week 40 was 6.5%-6.7% with orforglipron. 68%-73% of individuals on orforglipron achieved an HbA1c < 7%; 57%-62% of individuals achieved an HbA1c < 6.5%; and 17%-24% of individuals achieved an HbA1c < 5.7% (ie, below US criteria for prediabetes). Glycemic improvement was seen at as early as 4 weeks. Mean change in weight with orforglipron was -4.5% with the 3 mg dose, -5.8% with the 12 mg dose, and -7.6% with the 36 mg dose. Mean change in weight in the placebo group was -1.7%. 43%-61% of participants on orforglipron achieved a clinically meaningful weight loss of ≥ 5%; 15%-30% of participants lost ≥ 10% of their body weight; and 4%-10% of participants lost ≥ 15% of their body weight. The researchers also observed improvements in other cardiometabolic markers, including lipids, waist circumference, and systolic blood pressure. The safety profile was consistent with that of the GLP-1 RA class as a whole; the most common adverse effects were gastrointestinal side effects that were mild to moderate and mostly occurred during dose escalation. The prevalence of gastrointestinal side effects generally decreased over time. No episodes of severe hypoglycemia or cases of pancreatitis occurred. There was no adverse liver signal seen in ACHIEVE-1. In fact, mean alanine transaminase and aspartate aminotransferase levels decreased during the trial. Discontinuation rates with orforglipron were also similar to those of the class. Whilst direct comparisons are unfair, since there are no published head-to-head trials, ACHIEVE-1 delivers results comparable to those of the similarly designed semaglutide 1 mg monotherapy study SUSTAIN-1. In conclusion, ACHIEVE-1 positions orforglipron as an efficacious oral GLP-1 RA with a favorable safety profile that could scale globally for the treatment of early T2D and weight management. This option could help reduce health inequalities, especially in low-income countries where factors like affordability, availability, and accessibility hinder the delivery of disease-modifying therapies for T2D. Orforglipron may also drive a change in treatment paradigms and be considered as a first-line therapy for patients with early T2D and overweight or obesity. Further orforglipron studies awaiting completion include comparisons to dapagliflozin (ACHIEVE-2) and oral semaglutide (ACHIEVE-3), as well as ATTAIN, which will assess orforglipron for weight management in patients without T2D.
Medscape
17-06-2025
- Health
- Medscape
Bariatric Surgery Beats GLP-1 RAs for Sustained Weight Loss
Patients who underwent bariatric surgery experienced an approximately five times greater weight loss over 3 years than those who used weekly injections of GLP-1 receptor agonists (RAs) such as semaglutide and tirzepatide. METHODOLOGY: The use of GLP-1 RAs has surged over the years, but semaglutide and tirzepatide have rarely been directly compared with bariatric surgery, the gold standard for obesity and diabetes treatment. Researchers conducted a retrospective study using electronic health records to compare the weight-loss effects of injectable GLP-1 RAs (semaglutide or tirzepatide) with those of bariatric surgery on adults with BMI ≥ 35. They analyzed data of 38,545 patients who received GLP-1 RAs and 12,540 patients who underwent bariatric surgery via minimally invasive sleeve gastrectomy or Roux en-Y gastric bypass between 2018 and 2024. Percent total weight loss was compared over a 3-year follow-up period. TAKEAWAY: Patients who received GLP-1 RAs had significantly higher rates of diabetes, hyperlipemia, and chronic obstructive pulmonary disease than those who underwent surgery. After 3 years, patients who underwent bariatric surgery experienced a 23.3% total weight loss (95% CI, -23.5 to -23.1), whereas those who used GLP-1 RAs had a 4% total weight loss (95% CI, -4.1 to -3.8). Patients who used GLP-1 RAs continuously for 1 year lost 5.9% of their total weight, but weight loss was still significantly greater in those who underwent bariatric surgery (22.2%). IN PRACTICE: 'Clinical trials show weight loss between 15% to 21% for GLP-1s, but this study suggests that weight loss in the real world is considerably lower even for patients who have active prescriptions for an entire year. We know as many as 70% of patients may discontinue treatment within 1 year. GLP-1 patients may need to adjust their expectations, adhere more closely to treatment, or opt for metabolic and bariatric surgery to achieve desired results,' said the lead author in a news release. SOURCE: This study was led by Avery Brown, MD, a surgical resident at NYU Langone Health in New York City. It was presented on June 17, 2025, at the American Society for Metabolic and Bariatric Surgery 2025 Annual Scientific Meeting at the Gaylord National Resort & Convention Center in National Harbor, Maryland. LIMITATIONS: The authors did not report any specific limitations. DISCLOSURES: This study received support from a NYU Clinical and Translational Science Awards grant from the National Center for Advancing Translational Sciences and another grant from the National Institute of Allergy and Infectious Diseases.
Medscape
05-06-2025
- Business
- Medscape
GLP-1 Users Should Fast 24 Hours Before Anesthesia
Patients taking the new class of weight-loss drugs do not need to stop these medications prior to procedures requiring anesthesia, but they should adhere to longer preoperative fasting times, according to a new multidisciplinary consensus statement. The statement, led by the Society for Perioperative Assessment and Quality Improvement, recommends patients without significant gastrointestinal symptoms associated with glucagon-like peptide 1 receptor agonists (GLP-1 RAs) should fast from solid foods for 24 hours and stick to clear liquids prior to a procedure requiring anesthesia. This extended fasting time can help mitigate aspiration risk in these patients with delayed gastric emptying while retaining the benefits of continuing GLP-1 RAs, such as improved glycemic control. The statement is 'the first to provide recommendations for perioperative management of patients taking GLP-1 RAs based on an in-depth systematic literature review of both clinical perioperative studies and gastric emptying data,' Adriana Oprea, MD, the first author of the document, and her colleagues wrote. Changing Guidance In June 2023, the American Society of Anesthesiologists (ASA) released the first guidance statement regarding preoperative management of patients on GLP-1 RAs, after some case reports documented aspiration events in these patients. While the number of these events is generally low and rates of aspiration appear to be similar between patients on GLP-1 RAs and the general population, 'people got really worried with these drugs because of [the] delayed gastric emptying,' Oprea, an associate professor of anesthesiology at Yale School of Medicine in New Haven, Connecticut, told Medscape Medical News . The 2023 ASA guidance recommended holding GLP-1 RAs for one half-life — a week for patients on long-acting medication and a day for short-acting GLP-1s. Due to a lack of adequate evidence at the time, the document suggested these patients should follow the standard ASA fasting guidelines of 8 hours after a full meal. However, evidence suggests stopping GLP-1s for one half-life is not enough for the effects on gastric emptying to subside, according to the new statement. For longer-acting drugs like dulaglutide, semaglutide, and tirzepatide, patients would need to discontinue these medications for several weeks to restore normal gastrointestinal motility. For patients with type 2 diabetes, discontinuation of these medications over this period could lead to poor glycemic control, which is linked to worse postoperative outcomes. For patients taking GLP-1 RAs for weight loss, restarting these medications can result in increased gastrointestinal symptoms, Oprea said, such as nausea, vomiting, diarrhea, or constipation. 'Because adverse effects are more prevalent at higher GLP-1 RA doses, discontinuation of these medications might lead to a high likelihood of side effects upon medication reinitiation or require reinitiation of therapy at lower doses followed by dose reescalation,' Oprea's group wrote. 'This is logistically difficult for both patients and treating clinicians.' In October 2024, the ASA, along with other professional societies, published updated practice guidance stating GLP-1 RAs may be continued preoperatively in patients without an elevated risk for delayed gastric emptying and aspiration. Those defined as 'higher risk' included patients in the escalation phase, on weekly dosing, on higher doses, and with gastrointestinal symptoms. The guidance advised these patients at higher risk for delayed stomach emptying can help mitigate aspiration risk by following a 24-hour liquid diet. This updated guidance also received some criticism. 'As of yet, no studies have reported a difference in the incidence of increased residual gastric content that would justify treating patients differently on the basis of dose regimen and/or treatment phase,' wrote Glenio B. Mizubuti, MD, PhD, of the Kingston General Hospital, in Kingston, Ontario, Canada, and his colleagues in a letter to Anesthesiology . 'Similarly, the absence of ongoing digestive symptoms, while somewhat reassuring, should not be taken as a definitive sign of an empty stomach in GLP-1 RA users,' they wrote. Continue Meds, Extend Fasting Times This new consensus statement, published last month in the British Journal of Anaesthesia , recommends patients doing well on GLP-1 RAs should continue these medications preoperatively and follow a clear liquid diet for 24 hours before procedures requiring anesthesia. The recommendations were based on a systematic review of 112 studies and a modified Delphi process and were co-sponsored and endorsed by the American Association of Clinical Endocrinology. 'From our review of the literature, we feel that the fasting times are the most important factor that could decrease the risk of having residual gastric content in the stomach in a patient on GLP-1 RAs when they're scheduled to have a procedure that requires anesthesia,' Oprea said. The consensus also recommends patients on GLP-1s fast from high-carbohydrate-content clear liquids (containing 10% or more glucose) for 8 hours before and stop drinking any liquids four hours before these procedures. Inpatient and outpatients can restart GLP-1 RAs when they resume their original diets. Patients with significant gastrointestinal symptoms including severe nausea, vomiting, and inability to tolerate oral intake should postpone elective procedures that require anesthesia and refer to their prescribing physician for diet and medication modifications to manage symptoms, the authors advised. 'Our recommendation for a clear liquid diet for 24 hours preprocedurally might appear overly restrictive. However, evidence points to the safety of this approach in patients on GLP-1 RAs,' they wrote.
Medscape
05-06-2025
- Health
- Medscape
Patients With HS, Obesity Report Improvements With GLP-1 RAs
In a survey of 22 patients with hidradenitis suppurativa (HS), more than two thirds reported symptom improvement after treatment with glucagon-like peptide 1 receptor agonists (GLP-1 RAs). METHODOLOGY: Researchers conducted a cross-sectional survey of 22 adults (average age, 45 years; 90.9% women) with HS who were treated with GLP-1 RAs at the University of Pennsylvania's Dermatology Department between January 2019 and August 2024. Most participants were non-Hispanic (90.9%), 54.5% were Black, and 36.4% were White; 89.5% were classified as overweight or having obesity. GLP-1 RAs prescriptions were semaglutide (40.9%), tirzepatide (36.4%), dulaglutide (18.2%), or liraglutide (4.5%), with an average treatment duration of 17 months (range, 2-108 months). Primary outcomes were HS severity and quality of life. TAKEAWAY: Most participants (77.3%) achieved weight loss averaging 31 lb; 68.2% reported improvement in HS-specific health, while 31.8% reported no change in their condition. Patient-reported symptom improvements included reduced flares (61.9%), new lesions (66.7%), pain (52.4%), drainage (61.9%), itch (47.6%), and odor (42.9%). Common side effects included gastrointestinal symptoms, allergic reactions, headaches, menstrual spotting, and appetite suppression. Nearly 60% of patients reported that HS had less impact on their daily activities, with the same percentage stating they would recommend GLP-1 RAs to other patients. IN PRACTICE: 'These data suggest GLP-1 RAs may play an important adjunctive role in the treatment of HS, particularly given the high prevalence of obesity and diabetes in the HS population,' the study authors wrote. 'Randomized controlled studies with robust patient and dermatologist-reported endpoints,' they added, 'are needed to confirm these findings and establish clinical guidelines for use of GLP-1 RAs' in HS. SOURCE: The study was led by Radhika Gupta, BA, University of Pennsylvania, Philadelphia. It was published online on May 29 in JAAD International . LIMITATIONS: Study limitations included small size, lack of clinician assessment, high nonresponse rate, and potential recall bias. DISCLOSURES: The study received funding through a philanthropic gift for HS research. Gupta disclosed being a consultant for Cabaletta Bio. One author reported receiving research funding from Amgen, Boehringer Ingelheim, Cabaletta Bio, and InflaRx. Another author reported being a consultant for Sonoma Biotherapeutics, and the fourth author reported being a consultant for Vertex Pharmaceuticals.
