GLP-1 Weight Loss Drugs Linked to First National Decline in Obesity Rates, Survey Finds
Key Takeaways:
- The U.S. adult obesity rate has dropped from 39.9% to 37% over three years, coinciding with a rapid rise in GLP-1 medication use.
- Over 12% of adults now report taking injectable obesity drugs such as semaglutide or tirzepatide, more than double the proportion from early 2024.
- Experts warn that limited insurance coverage may soon hinder access, potentially reversing progress.
New survey suggests decline in U.S. obesity rates
The proportion of adults living with obesity in the United States has declined for the first time in years, according to a new Gallup National Health and Well-Being Index survey. The findings suggest that the surge in the use of injectable obesity drugs may be driving this shift.
The survey reported that 37% of U.S. adults are currently living with obesity, compared with a peak of 39.9% three years ago. Researchers attribute much of this reduction to the growing uptake of GLP-1 receptor agonists, a class of highly effective weight loss drugs that include semaglutide and tirzepatide.
Use of GLP-1 medications has more than doubled
The number of people using GLP-1-based treatments such as Ozempic and Wegovy (semaglutide), or Zepbound and Mounjaro (tirzepatide), has more than doubled over the past 18 months. According to Gallup, 12.4% of respondents reported using these drugs, up from 5.8% in February 2024, when the organisation first began tracking their use.
GLP-1 receptor agonists, which mimic a naturally occurring hormone that regulates appetite and blood sugar, were first approved for obesity treatment in 2021. Their mechanism of action involves acting on the brain and gut hormones to suppress hunger and slow digestion, helping individuals sustain weight loss.
A watershed in obesity treatment
Experts consider the introduction of GLP-1 receptor agonists to be a landmark in obesity treatment, following decades of limited progress through diet, exercise, and public health campaigns.
Gallup described the new generation of GLP-1 drugs as a “watershed in Americans’ long struggle to address obesity and related diseases.” Despite these advances, the survey also found that diabetes rates have reached a record high: 13.8% of adults reported having been diagnosed by a doctor or nurse. This highlights the scale of ongoing metabolic health challenges even as weight loss interventions improve.
Impact seen most among middle-aged adults and women
The data indicate that the reduction in obesity rates has been most notable among adults aged 40 to 64, a demographic more likely to use GLP-1 medications. Among those aged 50 to 64, obesity prevalence fell by 5.0 percentage points, reaching 42.8%.
The survey also noted differences by sex: women were more likely than men to use these medications and tended to report greater weight loss benefits. This aligns with previous clinical research showing that women are often more proactive in seeking medical support for weight management.
Access and affordability remain key challenges
Despite their effectiveness, access to GLP-1 drugs remains uneven and may worsen in the coming year. Dr Fatima Cody Stanford, an obesity specialist at Harvard University, cautioned that while the correlation between increased access and reduced obesity rates is promising, it may not be sustainable if coverage declines.
“I would say this correlation happened for those that had great coverage, but it’s going to be pulled back,” she said.
Dr Stanford explained that several private insurers – including those covering most of her patients – are planning to stop covering GLP-1 medications as of next year. Without insurance, the cost of injections typically reaches around $500 per month out of pocket, she noted.
Although pharmaceutical companies are developing oral versions that may eventually reduce costs, Dr Stanford warned that these treatments will likely remain unaffordable for many in the short term.
“While drugmakers are working to bring potentially less-expensive pill versions to market, it likely still will put the treatments out of reach for many,” she said.
Slow but significant progress
While the findings do not confirm causation, they offer one of the first indications that the widespread use of GLP-1 receptor agonists could be contributing to measurable declines in obesity prevalence. Public health experts stress, however, that long-term trends will depend heavily on sustained access, equitable prescribing, and broader changes in lifestyle and preventive care.
For now, the data mark a tentative but meaningful turning point in the decades-long fight against obesity in the United States – a shift that could influence obesity strategies worldwide if sustained.
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Semaglutide’s Cardioprotective Effects Extend Beyond Weight Loss, SELECT Trial Confirms
Key Takeaways:
- Semaglutide significantly reduced major adverse cardiovascular events (MACE) in adults with overweight or obesity and established cardiovascular disease, regardless of baseline body weight.
- Reductions in waist circumference contributed partly – but not fully – to the observed cardioprotective benefits, suggesting mechanisms beyond weight loss.
- Early divergence in cardiovascular outcomes between the semaglutide and placebo groups indicates that benefits emerge rapidly after treatment initiation.
Semaglutide’s impact on heart health goes beyond weight loss
A landmark study published in The Lancet has revealed that semaglutide, a Glucagon-Like Peptide 1 Receptor Agonist (GLP-1RA), offers cardiovascular protection in people with overweight and obesity that cannot be explained by weight loss alone. The findings come from the large-scale SELECT trial, which explored the drug’s effect on major adverse cardiovascular events (MACE) in individuals without diabetes but with established cardiovascular disease.
GLP-1 receptor agonists were originally developed for glycaemic control in type 2 diabetes but have since demonstrated additional benefits, including weight reduction and decreased cardiovascular risk. Obesity itself increases cardiovascular mortality and morbidity through metabolic, inflammatory, and haemodynamic pathways. However, simple measures such as body weight fail to differentiate between fat and lean mass or between subcutaneous and visceral fat – the latter being more strongly associated with cardiovascular disease.
Until now, the relationship between changes in adiposity induced by GLP-1RAs and subsequent cardiovascular outcomes has remained unclear.
About the SELECT trial
The SELECT trial was a randomised, double-blind, placebo-controlled, phase 3 study evaluating whether semaglutide, used alongside standard care, could reduce cardiovascular events in adults with overweight or obesity. The trial enrolled 17,604 participants aged 45 years or older with a body mass index (BMI) of at least 27 kg/m² and established cardiovascular disease (defined as a history of myocardial infarction, stroke, or symptomatic peripheral artery disease).
Participants were randomly assigned to receive either once-weekly semaglutide injections or a placebo, with a gradual 16-week dose escalation to a target of 2.4 mg from week 17 onwards. The primary endpoint was MACE – a composite measure including non-fatal myocardial infarction, non-fatal stroke, and cardiovascular death.
Researchers analysed both baseline measures of adiposity (including waist circumference and body weight) and treatment-induced changes over time. Associations between these factors and MACE were assessed using a Cox proportional hazards model, with additional analyses distinguishing early (week 20) and long-term (week 104) effects.
Key findings
The mean follow-up period was nearly 40 months, with participants exposed to semaglutide for an average of 33.3 months and placebo for 35.1 months. Across all baseline body habitus measures, semaglutide reduced MACE incidence compared with placebo.
Higher baseline BMI was associated with female sex, younger age, non-Asian nationality, higher blood pressure, prediabetes, and greater inflammatory burden. Within both study arms, individuals with lower baseline adiposity had a lower MACE risk. In the semaglutide group, MACE risk fell by approximately 4% for every 5 kg reduction in baseline weight, although this trend was not significant in the placebo group. For waist circumference, both groups showed a 4% lower risk per 5 cm smaller baseline measurement.
By week 20, the rate of first MACE events had already diverged between the groups (hazard ratio [HR] 0.58), demonstrating an early cardioprotective effect.
At this point, mean changes in body weight and waist circumference were −6.4% and −5.0 cm in the semaglutide group, compared with −0.8% and −1.1 cm in the placebo group. These early changes accounted for about 70% of the total reductions seen at week 104. Importantly, 11% of all MACE events occurred within the first 20 weeks of treatment.
In the semaglutide group, greater reductions in waist circumference were associated with a lower subsequent MACE risk (HR 0.91; 95% CI 0.84–0.98; p = 0.02), while weight loss alone was not linearly linked to reduced risk. Among placebo recipients, those who lost at least 5% of their weight experienced higher MACE incidence and all-cause mortality, possibly reflecting unintentional or illness-related weight loss.
At week 104, semaglutide recipients who achieved the greatest weight loss had the lowest MACE incidence, whereas placebo recipients with comparable weight loss had the highest.
Waist circumference emerged as a stronger predictor
Analyses indicated that waist circumference reduction was a partial mediator of semaglutide’s cardiovascular benefits. Accounting for early changes in waist circumference reduced the treatment hazard ratio from 0.80 to 0.86 – suggesting that about one-third (33%) of the cardioprotective effect could be attributed to reduced abdominal fat, while the remainder likely involves other physiological mechanisms.
Crucially, time-varying changes in overall weight did not mediate the observed cardiovascular outcomes, underscoring that semaglutide’s heart-protective properties extend beyond simple weight loss.
Implications and limitations
The authors concluded that semaglutide was superior to placebo in reducing cardiovascular risk across all baseline weight and waist circumference levels, and that its benefits became evident early in treatment. They emphasised that early body weight reductions did not independently explain these benefits.
They cautioned, however, that analyses performed after randomisation were exploratory and not causal. The predominantly White, male study population also limits generalisability to broader groups, including women and ethnically diverse populations.
Despite these caveats, the findings strengthen the evidence that semaglutide’s cardioprotective effects go beyond adiposity reduction, pointing to additional metabolic, vascular, or anti-inflammatory mechanisms.
The SELECT trial was funded by Novo Nordisk, and is registered under ClinicalTrials.gov identifier NCT03574597.
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GLP-1 Receptor Agonists May Reduce Rheumatoid Arthritis Activity and Cardiovascular Risk in People with Obesity
Key Takeaways:
- GLP-1 receptor agonists were linked to reduced rheumatoid arthritis (RA) disease activity and improved cardiovascular risk factors in people with obesity or overweight.
- Significant improvements were observed in inflammation markers, weight, and cholesterol levels over 12 months of treatment.
- Findings suggest GLP-1RAs could offer dual benefits by addressing both metabolic and inflammatory disease processes in RA.
GLP-1RAs show promise in managing RA and cardiometabolic health
The use of glucagon-like peptide-1 receptor agonists (GLP-1RAs) was associated with improvements in both rheumatoid arthritis (RA) disease activity and cardiovascular risk factors among people living with overweight or obesity, according to new research published in ACR Open Rheumatology.
Rheumatoid arthritis frequently coexists with obesity, which is known to exacerbate systemic inflammation, increase disease activity, and reduce response to treatment. Although GLP-1RAs are well established for treating obesity, type 2 diabetes, and for reducing cardiovascular risk, their potential role in inflammatory diseases such as RA has not been clearly defined.
Study overview
Researchers at the University of California, Los Angeles (UCLA) conducted a single-centre, retrospective observational study involving people with RA and a body mass index (BMI) of at least 27 kg/m². Participants were prescribed either semaglutide (oral or subcutaneous) or tirzepatide (subcutaneous) between 2018 and 2024.
Out of 554 screened individuals, 229 met the inclusion criteria. Of these, 173 took the prescribed GLP-1RA and formed the treatment cohort, while 42 individuals served as controls, having been prescribed but not initiating therapy. Participants were evaluated at 3-month intervals for up to 12 months.
Baseline characteristics
Both groups were broadly similar in terms of BMI, RA duration, and the use of conventional, biologic, or targeted synthetic disease-modifying antirheumatic drugs (DMARDs). However, diabetes (49% vs 14%) and hypertension (57% vs 38%) were more common in the treatment group.
The mean baseline BMI was 37.1 kg/m² among those receiving treatment and 35.3 kg/m² among control individuals. A greater proportion of participants in the treatment group were White (71% vs 47%).
Improvements in RA and cardiometabolic outcomes
People who took GLP-1RAs showed significantly greater improvements in several clinical measures compared with those who did not initiate therapy:
- RA disease activity scores: decreased by −0.03 versus an increase of +0.21 in controls (P = .03)
- Visual analogue scale (VAS) pain scores: decreased by −0.6 cm versus an increase of +1.3 cm in controls (P < .001)
- Weight: reduced by −6.2 kg versus −1.7 kg (P < .001)
- Total cholesterol: decreased by −10.3 mg/dL versus +0.3 mg/dL (P = .04)
- HbA1c: reduced by −0.4% versus +0.1% (P = .03)
Within the treatment group, significant reductions were also noted in inflammatory and lipid parameters, including:
- Erythrocyte sedimentation rate (ESR): −5.4 mm/hr (P = .004)
- C-reactive protein (CRP): −0.9 mg/dL (P = .004)
- Low-density lipoprotein (LDL) cholesterol: −7.3 mg/dL (P = .002)
- Triglycerides: −10.5 mg/dL (P = .004)
Tolerability and limitations
Adverse effects were relatively common, with 29% of participants discontinuing treatment, most frequently due to gastrointestinal symptoms or insurance-related issues.
Sensitivity analyses that accounted for comorbidities and serostatus did not significantly alter the study’s outcomes. However, researchers noted several limitations, including the single-centre, retrospective design, reliance on chart abstraction rather than validated disease activity indices, and the possibility of residual confounding.
Clinical implications
“Going forward, clinicians may consider integrating GLP-1RAs into the treatment regimens for patients with [RA and obesity], not only to target obesity-related complications but also possibly to target the underlying inflammatory disease process,” the authors concluded.
Some study authors disclosed affiliations with biotechnology, pharmaceutical, and medical device companies. A full list of disclosures is available in the original publication.
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Use of GLP-1 Drugs Soars Among People Undergoing Bariatric Surgery, Study Finds
Key Takeaways:
- The use of GLP-1 receptor agonists such as semaglutide and tirzepatide among bariatric surgery patients increased sixteenfold between 2020 and 2024.
- Both people with and without Type 2 diabetes are increasingly using these drugs, showing a shift toward combination approaches in obesity management.
- Researchers emphasise the importance of multidisciplinary care and call for evidence-based guidelines to optimise the use of GLP-1 drugs alongside surgery.
A rapid evolution in obesity care
New research has revealed a dramatic increase in the use of weight loss medications among people undergoing metabolic and bariatric surgery, signalling a major shift in the treatment of obesity and Type 2 diabetes.
The study will be presented at the American College of Surgeons (ACS) Clinical Congress 2025, held in Chicago from 4–7 October.
“There is no one-size-fits-all approach to treating obesity, metabolic syndrome, or diabetes and its related conditions,” said Dr Patrick J. Sweigert, senior author of the study and bariatric and foregut surgeon at The Ohio State University Wexner Medical Center in Columbus, Ohio. “We are entering a new world of multidisciplinary care pathways and a new frontier of weight management that is important for patients and surgeons to think about.”
About the study
The research team conducted a large cross-sectional study examining the use of glucagon-like peptide-1 receptor agonists (GLP-1RAs) – specifically semaglutide (marketed as Wegovy and Ozempic) and tirzepatide (marketed as Zepbound and Mounjaro) – among people undergoing metabolic and bariatric surgery.
Using data from the Epic Cosmos database, which aggregates over 300 million patient records from healthcare institutions across the United States, Dr Sweigert and colleagues analysed nearly 365,000 individuals who underwent primary metabolic and bariatric surgery between 2018 and 2024.
The study assessed prescription patterns for semaglutide and tirzepatide, two of the most widely prescribed GLP-1RAs, to understand how their use has evolved before surgery.
Key findings
Preliminary findings showed a striking rise in GLP-1 prescriptions in the year preceding surgery – from 1.8% in early 2020 to 29.4% by the end of 2024, representing a sixteenfold increase.
Importantly, the surge was seen among people both with and without Type 2 diabetes, demonstrating the expanding role of GLP-1 drugs in obesity treatment beyond diabetes management.
Among those without Type 2 diabetes, use of GLP-1 drugs before surgery increased elevenfold – from 2.1% in early 2022 to 23.2% by late 2024. For those with Type 2 diabetes, preoperative use quadrupled – from 11.3% to 45.2% over the same period.
The median age of participants was 43 years, with a median preoperative body mass index (BMI) of 46. Women accounted for 80% of the cohort, and 33% had a diagnosis of Type 2 diabetes.
Changing perceptions and treatment pathways
Lead author Dr Stefanie C. Rohde, a general surgery resident at The Ohio State University Wexner Medical Center, explained that the findings represent an evolution in how people view their treatment options for obesity.
“While patients previously believed they had to choose between GLP-1 receptor agonists and surgery, we are now seeing that people are using both,” said Dr Rohde. “We know that patients can use GLP-1s after bariatric surgery to amplify their weight loss. But all of this is still very new in terms of how to manage patients effectively.”
She added that real-world data such as that provided by the Epic Cosmos network could play a critical role in establishing evidence-based clinical guidelines for how and when to integrate GLP-1 therapies – whether before surgery, in combination with it, or during postoperative follow-up.
Limitations and next steps
The researchers acknowledged several limitations. As with many analyses of large health databases, there may be inaccuracies in medical record data. The study was also unable to confirm whether individuals filled or took their prescribed medications, which could affect the reliability of prescription data.
Despite these caveats, the authors believe the study offers valuable insights into emerging trends in combined pharmacological and surgical approaches to obesity care.
Study co-author Mahmoud Abdel-Rasoul, MS, MPH, contributed to the data analysis and interpretation.
Looking ahead
The rapid rise in GLP-1 use among bariatric surgery candidates reflects a broader transformation in obesity treatment – one increasingly characterised by personalised, multidisciplinary, and data-informed care.
As Dr Sweigert noted, “We are entering a new world of multidisciplinary care pathways.” The challenge now lies in defining the most effective, safe, and sustainable ways to integrate these groundbreaking medications into established surgical treatment frameworks.
CCH insight:
These findings from the ACS, showing GLP-1 drug use prior to bariatric surgery, follow on from another study showing that many patients use GLP-1 drugs after surgery, in order to prevent weight regain. This will hopefully help to shift the thinking around obesity treatment. There is still a common perception that patients with obesity have the option of medication or bariatric surgery, and that it is a ‘one-and-done’ treatment. However, we know that obesity is a complex, chronic, relapsing disease which requires a long-term, multi-disciplinary approach. So we need medications, we need surgery and we need behavioural support and other interventions, used together in various combinations, at different times, to provide the life-long care that obesity patients require.
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Bariatric Surgery Delivers Greater Long-Term Benefits Than GLP-1 Medicines Alone, Cleveland Clinic Study Finds
Key Takeaways:
- People with obesity and type 2 diabetes who underwent bariatric surgery lived longer and experienced fewer serious complications than those treated with GLP-1 receptor agonist medicines alone.
- Surgery was associated with a lower risk of death, cardiovascular disease, kidney disease, and diabetes-related eye damage over a 10-year period.
- Patients who had surgery lost more weight, achieved better blood sugar control, and relied less on medications for diabetes, blood pressure, and cholesterol.
Major Cleveland Clinic study compares treatments
A large-scale study conducted by Cleveland Clinic has shown that people living with obesity and type 2 diabetes who undergo bariatric (metabolic) surgery experience significantly better long-term outcomes compared with those treated only with GLP-1 receptor agonist (GLP-1RA) medicines.
The research, published in Nature Medicine, followed nearly 4,000 patients and found that surgery was linked to longer life expectancy, greater weight loss, improved blood sugar control, and reduced reliance on diabetes and cardiovascular medicines.
“Even with today’s best medicines, metabolic surgery offers unique and lasting benefits for people with obesity and diabetes,” said Ali Aminian, M.D., Director of Cleveland Clinic’s Bariatric & Metabolic Institute and primary investigator of the study. “The benefits we observed went beyond weight loss. Surgery was linked to fewer heart problems, less kidney disease and even lower rates of diabetes-related eye damage.”
Study design and findings
The M6 study (Macrovascular and Microvascular Morbidity and Mortality after Metabolic Surgery versus Medicines) included 3,932 adults with both diabetes and obesity who received care at Cleveland Clinic over a period of up to 10 years.
- 1,657 participants underwent metabolic surgery, including gastric bypass or sleeve gastrectomy.
- 2,275 participants were treated with GLP-1 medicines such as liraglutide, dulaglutide, exenatide, semaglutide, and tirzepatide.
The median follow-up was 5.9 years (interquartile range 4.4–7.6 years).
Key outcomes:
At the 10-year mark, patients who underwent metabolic surgery had significantly better outcomes:
- 32% lower risk of death
- 35% lower risk of major adverse cardiovascular events (MACE), including heart attack, heart failure, or stroke
- 47% lower risk of chronic kidney disease (CKD)
- 54% lower risk of diabetes-related retinopathy (eye damage)
The 10-year cumulative incidence of all-cause mortality was 9.0% (95% CI 6.8–10.8%) in the metabolic surgery group, compared with 12.4% (95% CI 9.9–15.2%) in the GLP-1RA group (adjusted hazard ratio 0.68, 95% CI 0.48–0.96; P = 0.028).
The 10-year cumulative incidence of MACE was 23.7% (95% CI 20.0–27.6%) in the metabolic surgery group and 34.0% (95% CI 28.1–44.2%) in the GLP-1RA group (adjusted hazard ratio 0.65, 95% CI 0.51–0.82; P < 0.001).
On average:
- People who had surgery lost 21.6% of their body weight over 10 years.
- People treated with GLP-1 medicines lost 6.8% of their body weight.
- Haemoglobin A1c (HbA1c), a key marker of average blood sugar, improved by -0.86% with surgery compared with -0.23% with GLP-1 medicines.
In addition, surgery patients required fewer prescriptions for diabetes, blood pressure, and cholesterol management.
Expert perspectives
The findings underscore the long-term advantages of bariatric surgery even in the current era of advanced GLP-1 treatments.
“Even in the era of these powerful new drugs to treat obesity and diabetes, metabolic surgery may provide additional benefits, including a survival advantage,” said Steven Nissen, M.D., Chief Academic Officer of the Heart, Vascular & Thoracic Institute at Cleveland Clinic and senior author of the study.
Dr Aminian emphasised the importance of maintaining surgery as a treatment option:
“Our findings indicate that surgery should remain an important treatment option for obesity and diabetes. These long-term benefits are harder to achieve with GLP-1 medicines alone, as many patients stop using the medications over time.”
Study limitations and future research
The authors highlighted that the study was observational, not a randomised controlled trial. This means that while strong associations were observed, direct comparisons may be influenced by unmeasured factors.
In addition, the study did not focus exclusively on the most recent and highly effective GLP-1 medicines. The authors noted that future trials should directly compare metabolic surgery with newer GLP-1 therapies, such as semaglutide and tirzepatide, to help guide clinical decision-making.
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Oral GLP-1 Therapy Orforglipron Demonstrates Significant Weight Loss in Landmark Trial
Key Takeaways:
- The ATTAIN-1 phase III trial found that the oral GLP-1 drug orforglipron led to clinically meaningful weight loss and metabolic improvements in people living with obesity or overweight.
- Average weight loss reached 12.4% with the highest dose, alongside significant improvements in waist circumference, blood pressure, and lipid profiles.
- Orforglipron may provide a more accessible alternative for individuals reluctant to use injections or living in areas with limited cold-storage infrastructure.
A new oral alternative to injectable GLP-1 therapies
An investigational oral GLP-1 drug, orforglipron, has been shown to promote substantial weight loss and improve cardiovascular and metabolic health markers in a large, international phase III clinical trial. The ATTAIN-1 study, published on 17 September in The New England Journal of Medicine, was led by researchers from Weill Cornell Medicine, McMaster University, York University, and collaborating institutions.
The study enrolled 3,127 participants with obesity or overweight who had obesity-related complications such as hypertension. None of the participants had diabetes. Participants were randomised to receive a placebo or one of three daily oral doses of orforglipron – 6 mg, 12 mg, or 36 mg – alongside guidance on maintaining a healthy diet and regular physical activity.
Meaningful weight loss across all doses
Over 72 weeks, individuals treated with orforglipron experienced dose-dependent weight loss:
- 7.8% reduction in body weight with the 6 mg dose
- 9.3% reduction with the 12 mg dose
- 12.4% reduction with the 36 mg dose
By comparison, participants in the placebo group lost an average of just 2.1% of their initial body weight.
Adverse events were consistent with those observed for other GLP-1 receptor agonists, mainly mild to moderate gastrointestinal effects including nausea, vomiting, and diarrhoea.
Clinical and public health implications
“The findings suggest that orforglipron could offer an important new option for people with obesity, especially those reluctant to use injections or who live in places where cold storage for injectable medications is limited,” said Dr Louis Aronne, Director of the Comprehensive Weight Control Center and Sanford I. Weill Professor of Metabolic Research at Weill Cornell Medicine, who served as a lead investigator for the ATTAIN-1 trial.
“ATTAIN-1 represents another milestone in developing effective treatments for obesity. In addition, the distribution and storage of a small molecule is less expensive, and scalability is simpler. Given the worldwide demand, these are important factors in making treatment available to those in need,” Dr Aronne added.
Dr Aronne is also an internist specialising in diabetes and obesity at NewYork-Presbyterian/Weill Cornell Medical Center.
Improvements beyond weight loss
Although the weight reduction achieved with orforglipron was slightly lower than that typically seen with injectable GLP-1 therapies such as semaglutide or tirzepatide, the study reported robust cardiometabolic benefits. Participants on orforglipron demonstrated greater reductions in:
- Waist circumference
- Systolic blood pressure
- Non-HDL cholesterol and triglyceride levels
- Glycated haemoglobin (HbA1c)
These improvements underline the drug’s potential to reduce the risk of major obesity-related complications, including cardiovascular disease and type 2 diabetes.
Why oral GLP-1 drugs could be game-changing
Injectable GLP-1 drugs, which are peptide-based therapies, have already transformed obesity and type 2 diabetes management worldwide. When taken long-term, they can help people lose more than 15% of their body weight and substantially lower the risk of heart attack, stroke, kidney disease, and sleep apnoea.
However, injectable GLP-1 medications require cold storage and are vulnerable to breakdown by stomach enzymes if taken orally. Orforglipron is different – it is a “small-molecule” drug designed to be taken as a pill, potentially lowering costs and simplifying global distribution.
Study scope and sponsorship
The ATTAIN-1 trial was sponsored by Eli Lilly and Company, which manufactures orforglipron as well as the injectable GLP-1 drug tirzepatide (marketed as Mounjaro for type 2 diabetes and Zepbound for chronic weight management). The trial was conducted across 137 sites in nine countries, including the United States, Canada, Japan, Brazil, Spain, and Saudi Arabia.
Disclosure: Dr Louis Aronne serves as a paid consultant and advisory board member for Eli Lilly and Company.
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Higher Dose of Semaglutide Delivers Greater Weight Loss and Metabolic Improvements
Key Takeaways:
- Tripling the standard dose of semaglutide led to significantly greater weight loss and improved metabolic outcomes, without an increase in serious adverse effects.
- Participants on the higher dose achieved clinically meaningful reductions in body weight, waist circumference, and HbA1C levels, with nearly one-third losing 25% or more of their starting weight.
- Side effects were mostly mild and transient, suggesting that the higher dose may be a safe option for people requiring more intensive obesity treatment.
Landmark findings from the STEP UP trials
Tripling the standard dose of semaglutide – a widely prescribed glucagon-like peptide-1 receptor agonist (GLP-1RA) – resulted in markedly greater weight loss and cardiometabolic benefits, according to results from two large multicentre clinical trials led by UT Southwestern Medical Center. The studies, published in The Lancet Diabetes & Endocrinology, indicate that patients may be able to safely take a higher semaglutide dose than currently approved if they need to lose additional weight.
“Semaglutide and other drugs in its class have been life-changing for people living with obesity around the world. Our new findings suggest that increasing the dose can lead to even greater benefits and may be appropriate for some patients,” said study leader Dr Ildiko Lingvay, Professor of Internal Medicine in the Division of Endocrinology and in the Peter O’Donnell Jr. School of Public Health at UT Southwestern.
Context: The global obesity challenge
Obesity affects nearly one billion people worldwide, according to the World Health Organization, and is a major driver of conditions such as Type 2 diabetes, cardiovascular disease, certain cancers, and liver disease. GLP-1RAs, first authorised in the early 2000s, have transformed the management of Type 2 diabetes and, more recently, chronic weight management and cardiovascular risk reduction.
Semaglutide received approval from the US Food and Drug Administration (FDA) in 2017 for people with Type 2 diabetes and has since been approved at a 2.4 mg weekly dose for weight management in both the United States and European Union. While this dose can produce significant weight loss, many patients do not achieve their treatment goals.
The STEP UP trials: Design and participants
To explore whether higher doses could deliver additional benefits, researchers conducted two phase 3b clinical trials – STEP UP Diabetes and STEP UP Obesity – to compare the effects of a weekly 7.2 mg dose of semaglutide with the standard 2.4 mg dose and placebo.
In the STEP UP Diabetes trial, 512 adults with both obesity and Type 2 diabetes were randomly assigned to three groups:
- 307 participants received 7.2 mg semaglutide weekly.
- 103 participants received 2.4 mg semaglutide weekly.
- 102 participants received placebo.
Participants were followed for 72 weeks at 68 trial sites across eight countries in Europe, southern Africa, and North America, including UT Southwestern. All participants received counselling every four weeks to encourage reduced-calorie diets and increased physical activity.
Results: Substantial weight loss and metabolic gains
Weight loss outcomes
As seen in earlier studies, the standard 2.4 mg dose produced a mean weight loss of 10.4% of starting weight, compared with 3.9% in the placebo group. However, participants taking the higher 7.2 mg dose achieved an even greater mean weight loss of 13.2%.
In addition, those receiving 7.2 mg were significantly more likely to:
- Reach a 20% reduction in waist circumference – a key measure of cardiometabolic health.
- Achieve superior improvements in HbA1C, an indicator of blood sugar control.
Outcomes in people without type 2 diabetes
The STEP UP Obesity trial, which focused on people with obesity but without Type 2 diabetes, showed even more striking results. Nearly one-third of participants on the higher dose lost 25% or more of their starting weight, compared with 15% of those on the standard dose and none on placebo.
Safety profile and side effects
The most frequently reported side effects were gastrointestinal symptoms, such as nausea, diarrhoea, and constipation. These affected approximately half of participants taking semaglutide and about a quarter of those on placebo. Most symptoms occurred during the dose-escalation period and tended to diminish over time.
The only side effect reported more frequently in the higher dose group was dysaesthesia (a change in touch sensation), experienced by approximately 20% of participants taking 7.2 mg, compared with 5% of those on the lower dose. Importantly, there was no increase in serious adverse events associated with the higher dose.
“These findings reinforce the promise of semaglutide and other GLP-1RAs, with benefits that appear to increase at higher doses without compromising patient safety,” Dr Lingvay concluded.
Funding and disclosures
Both STEP UP trials were funded by Novo Nordisk A/S, the manufacturer of semaglutide. Dr Lingvay reports receiving personal consulting fees from Novo Nordisk.
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Ozempic and GLP-1 Drugs Added to WHO Essential Medicines List – What Healthcare Professionals Need to Know
The WHO has added GLP-1 receptor agonists (GLP-1RAs), often referred to as GLP-1 drugs, to its Essential Medicines List. This signals global recognition of their role in treating obesity and type 2 diabetes. From an educational perspective, this is a turning point. It will accelerate patient demand and prescribing opportunities for healthcare professionals worldwide. The question we must now ask is how to best prepare for their safe and effective use.
By Nigel Hinchliffe, CCH Director of Education
Global recognition of GLP-1 therapy
The World Health Organisation has just published its latest Essential Medicines List (EML) – the first since July 2023. One of the most notable new inclusions is GLP-1-based medications (such as Wegovy, Ozempic and Mounjaro) for type 2 diabetes and obesity treatments.
The EML is a list of over 500 medicines that the WHO consider essential to meet priority healthcare needs. These medicines should be available to all, affordable and of assured quality at all times. Medicines are selected based on public health relevance, evidence of benefits and harms, and with consideration of cost and affordability.
Four GLP-1RA drugs are now included in the EML:
- dulaglutide (Trulicity)
- liraglutide (Saxenda)
- semaglutide (Ozempic/Wegovy) and
- tirzepatide (Mounjaro/Zepbound)
Their inclusion confirms what many of you will already have observed in practice: these are no longer fringe therapies, but treatments you must be ready to encounter routinely.
What this means for healthcare professionals
This decision signals global recognition of GLP-1RAs as critical therapies for serious chronic conditions – for treating metabolic disorders. It stands in sharp contrast to the public narrative that too often frames them as cosmetic quick fixes.
For practitioners, this shift will likely be significant. It could mean more time spent answering patient questions, more conversations about eligibility, and in many cases more opportunities to prescribe. In fact, whether you are directly involved in prescribing or working alongside those who are, these changes will affect everyday clinical practice. The challenge is ensuring that you are not only ready to meet demand but also prepared to integrate these medicines safely and thoughtfully into care.
Access and affordability challenges
The inclusion of Ozempic and other GLP-1RA drugs on the WHO list of Essential Medicines also raises questions of equity. Will these medicines be available and affordable for people living with obesity and type 2 diabetes worldwide?
At present, access remains limited. In the private sector, costs and supply constraints limit use. On the NHS, access is further restricted by the tight eligibility criteria set by NICE.
But change is coming. Cost and supply barriers are likely to ease over the next few years, as patents expire and generic versions become available. For example, liraglutide’s European patents are due to expire in 2026, with dulaglutide following in 2027–2028. The WHO’s decision should encourage governments to prepare, influencing policies, funding and procurement to improve availability and access.
For the UK, this could be transformative. Increased availability and lower costs may prompt NICE to broaden eligibility, enabling wider GLP-1RA prescribing on the NHS. For those of us working in education, this presents both an opportunity and a responsibility: ensuring professionals are supported to use these therapies well.
Wider access would also bring system-wide benefits, since preventing complications of obesity and diabetes – from cardiovascular disease to cancer and liver disease – is both clinically sound and economically sensible.
For healthcare professionals, the question is not whether you will encounter these drugs, but how ready you will be to use them well.
Preparing for safe GLP-1RA prescribing
Recent media reports of people obtaining GLP-1RA drugs from private clinics, or even the black market, without adequate medical oversight show the risks of uncontrolled use. This has already led to poor outcomes and, in some cases, serious emergencies.
The WHO’s decision to classify these medicines as essential has the potential to change this picture. By embedding GLP-1RA prescribing within NHS pathways, particularly in NHS primary care, people living with type 2 diabetes and/or obesity will gain access to GLP-1RA therapy within structured, long-term, multi-modal care. But it also raises the stakes: safe prescribing depends on practitioners having the right preparation and confidence.
Many frontline healthcare professionals will need additional support to build this knowledge and confidence. These drugs were traditionally confined to diabetes management pathways. Their use in weight management and obesity care requires careful attention to contra-indications, side-effect management, dose optimisation, and integration with diet and lifestyle support.
Targeted education is one of the most effective ways to bridge this gap. High-quality CPD can equip you with the knowledge and skills to prescribe responsibly or to contribute meaningfully to treatment planning, even if you are not prescribing directly. For those seeking a practical starting point, CCH’s online course GLP-1RAs in Focus – Why Drugs Like Ozempic Work, offers a clear, evidence-based introduction in just two hours.
Looking ahead to 2026
Next year 2026, could mark a turning point in obesity and diabetes care. Recognition of GLP-1RA medications as essential medicines, combined with greater availability, will almost certainly increase both prescribing opportunities and patient demand.
As an educator, I see this as a moment to prepare. For healthcare professionals, the question is not whether you will encounter these drugs, but how ready you will be to use them well. By strengthening your knowledge and skills now, you will be best placed to meet the challenge – and to support patients in making the most of this new phase in care.
FAQs: Ozempic, GLP-1 drugs, and the WHO Essential Medicines List (2025)
Why did WHO add GLP-1 drugs to the Essential Medicines List?
The World Health Organisation (WHO) reviews medicines for the Essential Medicines List based on public health relevance, evidence of benefit, safety, and cost-effectiveness. GLP-1 receptor agonists, such as semaglutide and tirzepatide, were added in 2025 due to strong evidence that they improve outcomes in people with type 2 diabetes and obesity, reducing cardiovascular risk as well as supporting weight management and improving blood sugar control.
Which GLP-1 drugs are included on the WHO list?
The 2025 Essential Medicines List includes dulaglutide (Trulicity), liraglutide (Saxenda/Victoza), semaglutide (Ozempic/Wegovy), and tirzepatide (Mounjaro/Zepbound). These medicines were selected for their efficacy, safety, and potential to address the global burden of obesity and type 2 diabetes.
What does this mean for NHS access to GLP-1 therapies?
In the UK, NHS access to GLP-1 drugs is currently restricted by NICE eligibility criteria and supply limitations. The WHO decision does not directly change NHS policy, but it is likely to influence future guidance. As costs fall with the arrival of generic versions from 2026 onwards, NICE may broaden eligibility, making these treatments more widely available.
Are GLP-1 drugs safe for all patients?
GLP-1 therapies are effective but not suitable for everyone. Contra-indications include a history of certain endocrine conditions, while gastrointestinal side effects such as nausea are common during dose escalation. Safe prescribing requires clinical assessment, careful monitoring, and support with diet and lifestyle changes. This is why training and professional education are vital for healthcare providers.
Quick Links
Find the 2025: WHO Model List of Essential Medicines here.
Find a clear, evidence-based intro to GLP-1 drugs with the online course. Click here to explore GLP-1RAs in Focus – Why Drugs Like Ozempic Work.
About the Author
This article was written by Nigel Hinchliffe, Director of Education at the College of Contemporary Health (CCH). Nigel has extensive experience in clinical education, with a particular focus on obesity care and the safe integration of new therapies into practice. At CCH, he leads the development of evidence-based training programmes that support healthcare professionals in delivering high-quality, patient-centred care.
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