Tag: GLP-1 agonist

Categories : Metabolic DisordersTags :

GLP-1 Agonist Users Report Reduced Alcohol Cravings

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In social media posts on the community network Reddit, users reported reduced cravings for alcohol when taking drugs intended to treat Type 2 diabetes and obesity. Across a number of threads – with titles such as “Did scientists accidentally invent an anti-addiction drug?” and “I don’t know if this is a side effect but … Mounjaro makes me drink less!!!!!” – users reported a changing relationship with beer, wine, and liquor.

An analysis of those posts, together with a remote study of individuals with obesity who reported using semaglutide and tirzepatide, found that the drugs decreased cravings and reduced alcohol consumption, according to a study by Virginia Tech researchers published in Scientific Reports.

“These findings add to a growing literature that these medications may curb dangerous drinking habits,” said Warren Bickel, Virginia Tech Carilion Behavioral Health Research Professor at the Fralin Biomedical Research Institute at VTC and corresponding author.

Combing Reddit for users’ experiences

Scientists with the Fralin Biomedical Research Institute’s Addiction Recovery Research Center combined two different studies to build on existing research, including studies that showed the drugs were effective in reducing alcohol consumption in animal models.

The first was an analysis of more than 68 000 Reddit posts from 2009-23 that included terms linked to GLP-1 approved medications.

Semaglutide is a GLP-1 agonist, a class of drugs that reduce blood sugar and energy intake by mimicking the actions of hormones released after eating.

Among the keywords included in the search were Mounjaro, Wegovy, Ozempic, and Trulicity.

After cleaning the resulting data – such as eliminating comments with fewer than 100 characters – the set was narrowed to 33 609 posts from 14 595 unique users.

The study was unique in using Reddit to analyse the reported experience of thousands of users.

On examining alcohol-related discussions, researchers found that 962 individuals made 1580 alcohol-related posts.

Of those, 71.7% addressed reduced cravings, reduced usage, and other negative effects due to drinking.

In a second study, 153 participants who self-reported having obesity were recruited from various social media platforms.

Roughly a third of these participants represented the control group, a third were taking either a semaglutide injection or tablet, and a third were using tirzepatide.

Participants on semaglutide or tirzepatide reported drinking significantly fewer drinks, on average, than those in the control group who were not on any medication for diabetes or weight loss.

In addition, researchers found that both the average number of drinks and the odds of binge drinking were found to be significantly lower.

Results also found that the stimulative and sedative effects of alcohol intoxication are reduced when taking these medications.

“Participants reported drinking less, experienced fewer effects of alcohol when they did drink it, and decreased odds of binge drinking,” said Alexandra DiFeliceantonio, assistant professor at Fralin Biomedical Research Institute and one of the study’s co-authors.

Researchers believe theirs is the first published report following tirezepatide, sold under the brand name Mounjaro, which was approved in 2022 and is used for treatment of Type 2 diabetes and weight loss.

Why this matters

Case studies and reports in the popular press hint at the drugs’ unexpected side effect of reducing addictive behaviors, including the desire to consume alcohol.

The US Food and Drug Administration has approved only three medications to treat alcohol use disorder: disulfiram, naltrexone, and acamprosate.

They have shown only modest success, have poor compliance, and are underprescribed.

The authors suggest further randomized controlled trials to explore the therapeutic potential of GLP-1 agonists and GIP/GLP-1 combination drugs to treat alcohol use disorder, which affects 5.9% of individuals in the United States ages 12 and older.

In addition, the participants identified as mostly white and female, and further studies in more diverse populations are needed to examine sex and race differences.

“Although evidence supporting the use of these medications for alcohol use disorder is growing, the field still needs to learn considerably more about them, particularly in identifying the underlying mechanisms. We plan to contribute to that effort,” Bickel said.

The drugs are a promising development in the study of alcohol use disorder. Data from the National Survey on Drug Use and Health indicate 15.7 million people in the United States meet the criteria for the chronic, relapsing brain disorder that is a significant contributor to global mortality yet remains one of the most undertreated conditions, Bickel said.

Source: Virginia Tech

Categories : Metabolic DisordersTags :

Liraglutide Results in Increased Insulin Sensitivity Independent of Weight Loss

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A new Vanderbilt University study published in the journal Diabetes demonstrates that a glucagon-like peptide-1 receptor (GLP-1R) agonist, a member of a class of medication used to treat Type 2 diabetes and obesity, can lead to a rapid improvement in insulin sensitivity.

Insulin sensitivity is how responsive cells are to insulin; reduced insulin sensitivity or insulin resistance is a feature of Type 2 diabetes, so improving it can reduce the risk of developing the disease or improve its treatment.

GLP-1R agonists are medications that influence metabolism, such as decreasing blood sugar levels by promoting insulin secretion. Dipeptidyl peptidase 4 (DPP-4) inhibitors block the degradation of the body’s own endogenous GLP-1, as well as other peptide hormones such as glucose-dependent insulinotropic peptide (GIP).

“We know that GLP-1R agonists promote weight loss, but we were surprised to find that the GLP-1R agonist liraglutide also has rapid effects on insulin sensitivity, independent from weight loss,” said Mona Mashayekhi MD, PhD, assistant professor of Medicine in the Division of Diabetes, Endocrinology and Metabolism.

“This effect requires activation of the GLP-1 receptor, but increasing the body’s own endogenous GLP-1 through the use of the DPP4 inhibitor sitagliptin does not achieve similar effects.”

“Our research suggests that liraglutide, and presumably other GLP-1R agonists, are having important metabolic effects in a way that’s different from increasing endogenous GLP-1 levels, even though they’re using the same receptor. Future research will focus on potential mechanisms of how GLP-1R agonists are improving insulin sensitivity independent of weight loss.”

Eighty-eight individuals with obesity and pre-diabetes were randomized for 14 weeks to receive the GLP-1R agonist liraglutide, the dipeptidyl peptidase 4 (DPP-4) inhibitor sitagliptin, or weight loss without drug using a low-calorie diet.

To further investigate the GLP-1R-dependent effects of the treatments, the GLP-1R antagonist exendin and a placebo were given in a two-by-two crossover study during mixed meal tests.

Crossover studies allow the response of a subject to treatment A to be compared with the same subject’s response to treatment B.

Liraglutide was shown to rapidly improve insulin sensitivity as well as decrease blood glucose within two weeks of beginning treatment and before any weight loss.

“GLP-1R agonists are an exciting class of medications, given their strong glucose-lowering effects combined with tremendous weight-loss benefits, and they have transformed how we manage diabetes and obesity in the clinic,” Mashayekhi said.

“Since the number of medications in this class is rapidly expanding, a deeper understanding of the mechanisms of benefit is crucial so we can design the right drugs for the desired effects in the right patients.”

The investigators’ prior research demonstrated that liraglutide, but not sitagliptin or diet, improves measures of heart disease and inflammation.

This matches the clinical findings of reduced cardiovascular disease with GLP-1R agonist treatment.

Future studies will continue to explore both receptor- and weight loss-dependent effects of GLP-1R agonists in humans.

Source: Vanderbilt University Medical Center

Categories : Metabolic Disorders Obstetrics & GynaecologyTags :

Newer Diabetes Drugs don’t Increase Risk to Foetus

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Newer diabetes medicines do not appear to increase the risk of birth defects. The largest comparative study to date found no increased risk compared to treatment with insulin, which is considered safe during pregnancy. The study was published in JAMA Internal Medicine.

Newer diabetes drugs such as sulfonylureas, DPP-4 inhibitors, GLP-1 receptor agonists and SGLT2 inhibitors are being increasingly used, both in the treatment of diabetes, but also extended indications for several of the preparations. 

However, knowledge of the foetal effects of these drugs is still low, so women with type 2 diabetes are often advised to switch to insulin before a planned pregnancy because it is considered safe. However, not all pregnancies are planned and more and more people are becoming pregnant while being treated with these drugs.

An international research team has now investigated whether the use of these drugs during pregnancy increases the risk of birth defects. The researchers used health data from 3.5 million pregnancies in six different countries (Sweden, Norway, Finland, Iceland, USA and Israel) between 2009 and 2021. Among these 3.5 million women, nearly 52 000 were diagnosed with type 2 diabetes and more than 8000 took one of the newer diabetes drugs in the three months before or after their last menstrual period.

Diabetes itself poses a risk of birth defects. High blood sugar levels in early pregnancy, which are more common in people with diabetes, increase the risk of foetal malformations. Therefore, the researchers were not surprised to see a slightly elevated risk in this group.

Among women diagnosed with type 2 diabetes before pregnancy, 5.3% of babies were born with severe birth defects, including 2.2% with heart defects, compared to the overall group where 3.8% had severe birth defects and 1.3% with heart defects. 

No increased risk of birth defects

However, the researchers found that the women with diabetes treated with the newer diabetes drugs did not have a higher risk of giving birth to children with birth defects than the women with diabetes treated with insulin.

“It has already been shown that insulin is safe to use during pregnancy and that it does not cross the placenta. The increased risk of birth defects in the children of women with type 2 diabetes using the newer diabetes drugs is therefore very likely caused by the disease,” says first author Carolyn Cesta, Associate Professor at the Center for Drug Epidemiology at Karolinska Institutet.

Despite being the largest study in this field to date, covering more than 3.5 million pregnancies, relatively few women used the new diabetes drugs, and the researchers stress that further studies are needed to confirm the results. However, they note that the study still shows that these drugs do not pose a major risk of birth defects.

As type 2 diabetes becomes more common among women of childbearing age and as GLP-1 receptor agonists such as semaglutide (Wegovy, Ozempic) are approved to treat obesity, the number of exposed pregnancies is likely to increase. 

“Our findings provide a first indication of the safety of infants exposed to these medications during pregnancy,” says Carolyn Cesta.

Source: Karolinska Institutet

Categories : Metabolic DisordersTags :

Public Urged To Use Registered Ozempic Products

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Photos supplied by Novo Nordisk

The South African Health Products Regulatory Authority (SAHPRA) is aware of the falsified Ozempic products currently being sold on the market and online.

SAHPRA has been informed of advertisements regarding unauthorised Ozempic/semaglutide-containing products that are being disseminated through radio stations and social media platforms.

The Regulator is warning the public to be wary of products claiming to be Ozempic (semaglutide) which are not approved by SAHPRA.  

Ozempic is a Schedule 4, prescription-only medicine, authorised by SAHPRA only for the treatment of type 2 diabetes mellitus in adults. SAHPRA has not authorised/registered Ozempic for weight-loss, therefore, use in that regard would be off-label. It must be noted that only a healthcare practitioner can make a Schedule 4 product available off-label as they would provide the requisite guidance and support to the patient/individual.

Novo Nordisk South Africa, who is the Holder of Certificate of Registration (HCR) has confirmed a national shortage of Ozempic stock; this resulted in limited access to treatment for diabetic patients. This may have created an opportunity for falsified/counterfeit products flooding the market claiming to be Ozempic and being used off-label for weight loss. Consumers should be wary of online offers for products claiming to be Ozempic or semaglutide.

Currently, there are no generic versions of this medicine being lawfully manufactured. Therefore, any product not manufactured by Novo Nordisk claiming to contain semaglutide is likely to be fake or counterfeit. The public is being exposed to many different types of unregistered/unauthorised products that are either substandard or falsified thereby putting their health at risk. See examples of registered vs counterfeit products.

Registered products safe to use
Ozempic solution for injection is a registered product by SAHPRA belonging to the HCR, Novo Nordisk South Africa.

There are only two (2) registered presentations of the pre-filled pen for Ozempic available in South Africa namely, Ozempic 0,25 mg and 0,5 mg/dose pen and Ozempic 1 mg/dose pen.

What the public should know

  • Using unregistered semaglutide products claiming to have the effects of Ozempic bought from unverified/illegally trading suppliers could be detrimental to your health as these have not been evaluated by SAHPRA for safety, quality, and efficacy.
  • These falsified/fake Ozempic products may contain certain active ingredients found in the registered Ozempic products; however, the formulations or manufacturing processes may be different. These formulations have not been evaluated by SAHPRA.
  • SAHPRA urges the public to first consult their medical professionals for their health treatment and prescriptions, and only purchase or use SAHPRA registered/authorised products sold at registered pharmacies.
  • Any medicines that are bought outside of the legal supply chain:
    • May not contain any active ingredient.
    • May contain dangerous levels of the active ingredient.
    • May contain another active ingredient such as insulin instead of semaglutide.
    • May contain harmful inactive ingredients.
    • May be nonsterile and contaminated with microbes, therefore not suitable for injection.

“Protecting the health of South Africans is top of mind for the regulator. The scourge of unregistered, substandard, and falsified medicines on the market is a serious health risk for the public. SAHPRA is listening to the public concerns, and we have an ongoing investigation into these falsified Ozempic and unregistered semaglutide-containing products”, indicates SAHPRA CEO, Dr Boitumelo Semete-Makokotlela.

Public are urged to report any suspected products that are falsely claiming to work like Ozempic. You can report through these whistle blower platforms, SAHPRA’s 24-hour hotline (0800 204 307) or via our web reporting facility: .

Categories : Cancer Metabolic DisordersTags :

GLP-1 Agonists may Reduce Colorectal Cancer Risk

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By HualinXMN – Own work, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=133759262

A groundbreaking study by researchers at Case Western Reserve University suggests that glucagon-like peptide-1 receptor agonists (GLP-1 RAs), normally used to treat diabees, may also reduce the risk of colorectal cancer (CRC). The findings, published in the journal JAMA Oncology, support the need for clinical trials to determine whether these medications could prevent one of the deadliest types of cancers.

Eventually, the medications may also show promise in warding off other types of cancer associated with obesity and diabetes.

“Our results clearly demonstrate that GLP-1 RAs are significantly more effective than popular anti-diabetic drugs, such as Metformin or insulin, at preventing the development of CRC,” said Nathan Berger, the Hanna-Payne Professor of Experimental Medicine at the Case Western Reserve School of Medicine and the study’s co-lead researcher.

Glucagon-like peptide-1 receptor agonists, or GLP-1 RAs can lower blood-sugar levels, improve insulin sensitivity and help manage weight. They’ve also been shown to reduce the rates of major cardiovascular ailments. Importantly the protective effect of GLP-1 RAs are noted in patients with or without overweight/obesity.

“To our knowledge,” said co-lead researcher Rong Xu, a professor at the School of Medicine, “this is the first indication this popular weight-loss and anti-diabetic class of drugs reduces incidence of CRC, relative to other anti-diabetic agents.”

Berger and Xu are members of the Case Comprehensive Cancer Center.

In the US, the American Cancer Society estimates CRC is the third-leading type of cancer in both sexes, with 153 000 new cases per year. It is also the second-leading cause of cancer mortality with 52 550 deaths per year.

Since GLP-1 RAs have been shown to be effective anti-diabetic and weight-loss agents, the researchers hypothesized they might reduce incidence of CRC.

Using a national database of more than 100 million electronic health records, the researchers conducted a population-based study of more than 1.2 million patients.

These individuals had been treated with anti-diabetic agents from 2005-19; the CWRU team examined the effects of GLP-1 RAs on their incidence of CRC, as compared to those prescribed other anti-diabetic drugs.

Population-based research means matching as many people as possible with the same characteristics, such as sex, race, age, socio-economic determinants of health and other medical conditions, to accurately compare the drug’s effects.

Among 22 572 patients with diabetes treated with insulin, there were 167 cases of CRC. Another 22 572 matched patients treated with GLP-1 RAs saw 94 cases of CRC. Those treated with GLP-1 RAs had a 44% reduction in incidence of CRC.

In a similar comparison of 18 518 patients with diabetes treated with Metformin, compared to 18 518 patients with diabetes treated with GLP-1 RAs, had a 25% reduction in CRC.

“The research is critically important for reducing incidence of CRC in patients with diabetes, with or without overweight and obesity,” Berger said.

Source: Case Western Reserve University

Categories : Gastrointestinal Surgeries & ProceduresTags :

Hold the GLP-1 Agonists Before Surgery, New Advice Says

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Patients taking Glucagon-like peptide-1 (GLP-1) receptor agonists should stop taking them before they have surgery, due to the risk of aspirating while under general anaesthesia. This is the latest advice from the American Society of Anesthesiologists (ASA).

Initially approved by the Food and Drug Administration (FDA) for type 2 diabetes mellitus and cardiovascular risk reduction, GLP-1 agonists have shot up in popularity due to their effectiveness in weight loss. Despite having recent FDA approval, they have been used off-label for this purpose for quite some time.

When it comes to surgery, a number of organisations have recommended to hold these drugs either the day before or day of the procedure. For patients on weekly dosing, it is recommended to hold the dose for a week, the ASA notes.

GLP-1 agonists are associated with adverse gastrointestinal effects such as nausea, vomiting and delayed gastric emptying. The effects on gastric emptying are reported to be reduced with long-term use, most likely through rapid tachyphylaxis at the level of vagal nerve activation. Based on recent anecdotal reports, there are concerns that delayed gastric emptying from GLP-1 agonists can increase the risk of regurgitation and pulmonary aspiration of gastric contents during general anaesthesia and deep sedation. Patient taking GLP-1 agonists are more likely to have increased residual gastric contents as predicted by adverse gastrointestinal symptoms (nausea, vomiting, dyspepsia, abdominal distension).

The use of GLP-1 agonists in paediatrics has primarily been reported for the management of type 2 diabetes mellitus and obesity. The published literature on GLP-1 agonists in paediatrics is predominantly from paediatric patients 10 to 18 years old and concerns are similar to those reported in adults. During the conduct of general anaesthesia/deep sedation, children on GLP-1 agonists have similar gastrointestinal adverse events at a rate similar to adults.

In a review of the literature, the ASA Task Force on Preoperative Fasting found that, beyond a few case reports, there was little evidence for guidance on preoperative management of GLP-1 agonists. Nevertheless, they made recommendations for elective procedures. In the case of urgent or emergent procedures, they suggested treating the patient as ‘full stomach’.

If the patient’s GLP-1 agonists prescribed for diabetes management are held for longer than the dosing schedule, the guidelines urge surgeons to consider consulting an endocrinologist for bridging the antidiabetic therapy in order to avoid hyperglycaemia.

They further recommend that if gastrointestinal symptoms, such as severe nausea/vomiting/retching, abdominal bloating, or abdominal pain, are present, surgeons should consider delaying elective procedures. If the patient has no gastrointestinal symptoms and the GLP-1 agonists have been held as advised, the surgical team can carry on as normal.

Source: American Society of Anesthesiologists

Categories : Gastrointestinal Metabolic DisordersTags :

For Weight Loss, the Side Effects of GLP-1 Agonists can be Hard to Stomach

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GLP-1 agonists are being lauded as game-changers in the fight against obesity, but GLP-1 agonist drugs like semaglutide may come with a heightened risk of severe gastrointestinal problems, according to new research published in JAMA.

Designing their study for the side effects rather than the efficacy of the drugs, the researchers found that GLP-1 agonists are associated with an increased risk of serious medical conditions including gastroparesis (stomach paralysis), pancreatitis and bowel obstruction.

While previous studies highlighted some of these risks in patients with diabetes, this study from the University of British Columbia is the first large, population-level study to examine adverse gastrointestinal events in non-diabetic patients using the drugs specifically for weight loss.

“Given the wide use of these drugs, these adverse events, although rare, must be considered by patients thinking about using them for weight loss,” said first author Mohit Sodhi, a graduate of UBC’s experimental medicine program and fourth year UBC medical student studying the adverse events of commonly prescribed medications. “The risk calculus will differ depending on whether a patient is using these drugs for diabetes, obesity or just general weight loss. People who are otherwise healthy may be less willing to accept these potentially serious adverse events.”

GLP-1 agonists have exploded in popularity over the past decade as an off-label weight-loss tool, reaching approximately 40 million prescriptions in the US in 2022.

It was only in 2021 that some forms of the medications were approved as a treatment for obesity. However, randomised clinical trials examining the efficacy of the medications for weight loss were not designed to capture rare gastrointestinal events due to their small sample sizes and short follow-up periods.

“There have been anecdotal reports of some patients using these drugs for weight loss and then presenting with repeated episodes of nausea and vomiting secondary to a condition referred to as gastroparesis,” said senior author Dr Mahyar Etminan, an epidemiologist and associate professor in the department of ophthalmology and visual sciences at the UBC faculty of medicine. “But until now, there hasn’t been any data from large epidemiologic studies.”

To help fill this knowledge gap, UBC researchers examined health insurance claim records for approximately 16 million US patients and looked at people prescribed either semaglutide or liraglutide, two main GLP-1 agonists, between 2006 and 2020. They included patients with a recent history of obesity, and excluded those with diabetes or who had been prescribed another antidiabetic drug.

The researchers analysed the records to see how many patients developed one of four gastrointestinal conditions, and compared that rate to patients using another weight-loss drug, bupropion-naltrexone. Compared to bupropion-naltrexone, GLP-1 agonists were associated with a:

  • 9.09 times higher risk of pancreatitis, which can cause severe abdominal pain and, in some cases, require hospitalisation and surgery.
  • 4.22 times higher risk of bowel obstruction, resulting in symptoms like cramping, bloating, nausea and vomiting. Depending on the severity, surgery may be required.
  • 3.67 times higher risk of gastroparesis, limiting the passage of food from the stomach to the small intestine and results in symptoms like vomiting, nausea and abdominal pain.

Additionally, the study found a non-significant higher incidence of biliary disease.

The researchers say that although the events are rare, with millions around the world using the drugs, it could still lead to hundreds of thousands of people experiencing these conditions.

“These drugs are becoming increasingly accessible, and it is concerning that, in some cases, people can simply go online and order these kinds of medications when they may not have a full understanding of what could potentially happen. This goes directly against the mantra of informed consent,” said Sodhi.

In the meantime, the researchers hope that regulatory agencies and drug makers will consider updating the warning labels for their products, which currently don’t include the risk of gastroparesis.

“This is critical information for patients to know so they can seek timely medical attention and avoid serious consequences,” said Sodhi.

Source: University of British Columbia

Categories : Cardiovascular Disease Metabolic DisordersTags :

Semaglutide Also Cuts Cardiovascular Risk, Could Change Cardiology Practice

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By HualinXMN – Own work, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=133759262

According to results from the SELECT trial run by Novo Nordisk, semaglutide dramatically reduces the risk of major adverse cardiovascular events (MACEs) in addition to its obesity benefits. This is bolstered by the results of another trial, STEP-1, which also suggested significant reduction in future cardiovascular events. These results have captured the attention of researchers, who commented in Nature that they could change the practice of cardiology.

Semaglutide, sold in the US for the treatment of both obesity (Wegovy) and diabetes (Ozempic), is an agonist for glucagon-like peptide 1 (GLP-1), a hormone associated with appetite.

”It’s hard to think of other [drugs], apart from statins, that have shown such a profound effect,” says Martha Gulati, director of preventive cardiology at Cedars-Sinai Medical Center in Los Angeles, USA.

It was expected that semaglutide would have cardiovascular benefits through promoting weight loss, but evidence shows that drugs mimicking GLP-1 can improve fatty-acid metabolism and reduce inflammation, for example, says Gulati. “This is what’s so fascinating about these drugs. They work on the brain, the pancreas, the cardiovascular system, the gastrointestinal tract … There’s more to them than simply weight loss.”

Recent studies have been encouraging in terms of semaglutide’s benefits for reducing cardiovascular disease risk. Earlier this month, Novo Nordisk announced the headline results from the SELECT cardiovascular outcomes trial. The double-blinded trial compared subcutaneous once-weekly semaglutide 2.4mg with placebo as an adjunct to standard of care for prevention of MACEs over a period of up to five years. The trial enrolled 17 604 adults aged 45 years or older with overweight or obesity and established cardiovascular disease (CVD) with no prior history of diabetes.

The trial showed 20% reduction in MACEs for people treated with semaglutide 2.4mg compared to placebo. The primary endpoint was a composite outcome of the first occurrence of MACE cardiovascular death, non-fatal myocardial infarction or non-fatal stroke. All three of these components contributed to the MACE reduction. 1270 first MACEs were accrued.

Expanding GLP-1 analogues to cardiovascular disease prevention may not be without challenges, as the European Medicines Agency opened investigations into semaglutide and liraglutide over reports of suicidal thoughts and self-harm.

A separate study based on the STEP 1 trial data found that 93 million adults in the US could benefit from semaglutide, from a combination of weight loss and reduced cardiovascular benefits. They estimate a reduction in relative risk of 18% with the drug.