Tirzepatide may change how the body uses energy

 

Anti-obesity medication activates brown adipose tissue that burns calories

Reports and Proceedings

The Endocrine Society

FacebookXLinkedInWeChatBlueskyMessageWhatsAppEmail

Chicago—Tirzepatide doesn’t just help people lose weight; it also activates brown adipose tissue, representing a major milestone in obesity research, according to a study being presented Monday at ENDO 2026, the Endocrine Society’s annual meeting in Chicago, Ill.

Until now, tirzepatide’s weight-loss effect has been attributed primarily to reduced appetite, leading to smaller portions.

“In the TABFAT trial, we asked a different question: beyond eating less, does tirzepatide also change how the body burns energy—specifically through brown adipose tissue, a metabolically active type of fat that produces heat and consumes calories?” said Rok Herman, M.D., from the Department of Endocrinology, Diabetes and Metabolic Diseases at University Medical Centre Ljubljana in Ljubljana, Slovenia.

Brown adipose tissue was long thought to disappear after infancy and was only confirmed in adult humans through imaging studies in the late 2000s. It is markedly suppressed in obesity, and until now, moderate cold exposure has been its strongest known activator.

In a randomized, placebo-controlled clinical trial in premenopausal women with obesity, Herman and colleagues used cold-stimulated PET/CT imaging and MRI scans to measure brown adipose tissue activity before and after 24 weeks of treatment.

“We found that tirzepatide significantly increased brown adipose tissue activity and volume, and it also showed potential signs of converting white subcutaneous fat into more metabolically active ‘beige’ fat,” Herman said.

Tirzepatide increased PET/CT-detectable brown adipose tissue activity from 41.2% to 64.7% of participants, while no comparable change was seen in the placebo group. “We were also encouraged by the consistency of the signal across other imaging modalities employed in the study that may capture different component of brown fat biology,” Herman added.

“This adds a new layer to how we understand the new generation of anti-obesity medications,” Herman said. “They are not only appetite suppressants— tirzepatide also appears to modulate energy expenditure at the tissue level, opening a plausible path toward future therapies that combine appetite regulation with thermogenic activation.”

Herman suggests that future research measure, study, and potentially enhance the use of brown and beige fat activity as a specific target for a tailored approach to obesity care.

Semaglutide can have lifetime cost and health benefits for non-diabetic overweight or obese

 

 individuals with heart disease

A detailed analysis in the Canadian Journal of Cardiology of the cost-effectiveness of semaglutide shows that with price reductions, it could meet the benchmark for healthcare value, urging policymakers to consider long-term gains in budgeting decisions

Peer-Reviewed Publication

Elsevier

FacebookXLinkedInWeChatBlueskyMessageWhatsAppEmail

 

image: 

The value proposition in contemporary health and disease care: A study published in the Canadian Journal of Cardiology into the cost-effectiveness of the use of semaglutide in overweight or obese individuals without diabetes, but with pre-existing cardiovascular disease, shows that semaglutide (Ozempic, Wegovy) is not cost-effective at current pricing, but can be in the long-term with price reductions or rebates.

view more 

Credit: James Stone/Ana Johnson, Canadian Journal of Cardiology

For overweight or obese individuals without diabetes, but with pre-existing cardiovascular disease, semaglutide (Ozempic, Wegovy) is not cost-effective at current pricing, new research shows. However, with price reductions or rebates up to 50%, it could meet the benchmark for value in healthcare. An article in the Canadian Journal of Cardiology, published by Elsevier, details a statistical model analyzing the cost-effectiveness of semaglutide. It provides evidence for policymakers considering the benefits of funding semaglutide for individuals without diabetes and the budgetary impact for long-term health gains.

Obesity is a global epidemic. By 2035, more than half of the world is expected to be overweight or obese. Being overweight or obese is associated with increased risk of adverse cardiovascular events even after considering metabolic risk factors, and more than two thirds of deaths related to elevated body mass index (BMI) are caused by cardiovascular diseases.

The demand for semaglutide, a glucagon-like peptide 1 receptor agonist (GLP-1 RA) commonly known under the brand names Ozempic and Wegovy, has surged in recent years, especially for weight loss. It not only regulates blood sugar, but also reduces appetite and slows digestion. In Canada, it is currently only funded for individuals with diabetes. Researchers from the University of Calgary undertook a statistical analysis to estimate the lifetime benefit and costs of semaglutide use compared to no semaglutide use in overweight or obese individuals without diabetes, but with pre-existing cardiovascular disease.

Lead investigator Derek Chew, MD, MSc, Cumming School of Medicine, University of Calgary, explains, "Our economic model compared the difference in lifetime costs (including drug costs, hospitalizations, and other significant health events) and difference in life expectancy adjusted for patient quality of life between those treated with semaglutide and those who did not receive semaglutide. The main finding is that at current pricing, semaglutide is not cost-effective. However, with price reductions or rebates of up to 50%, semaglutide could meet the benchmark for value in healthcare."

The study's decision analysis entailed utilizing an analytical framework, tracking probabilities of different disease states, and data from the SELECT trial (Semaglutide Effects on Cardiovascular Outcomes in People with Overweight or Obesity, which showed the cardiac benefits for non-diabetic individuals in the studied cohort using weekly semaglutide injections) to identify the incremental cost-effectiveness ratios and quality-adjusted life years (QALYs) gained from semaglutide therapy for the treatment of obesity versus usual care.

Using the conventional benchmark of CAN$50,000/QALY gained (i.e., CAN$50,000 or less to increase a person’s quality of life and/or life expectancy by one year is considered acceptable healthcare value for money), the base case analysis demonstrated that the incremental cost-effectiveness ratio for semaglutide compared to standard care was CAN$72,962/QALY gained with a 14% probability of meeting the CAN$50,000/QALY benchmark. Factors with the greatest impact on estimated cost-effectiveness were medication impact on mortality and medication cost. When the price of semaglutide was reduced by 50%, it was economically attractive at CAN$37,190/QALY gained with an 80% likelihood of cost-effectiveness at a CAN$50,000/QALY threshold.

Co-lead investigator Elissa Rennert-May, MD, Cumming School of Medicine, University of Calgary, notes, "Our study's results are important because public drug plans are considering whether to fund GLP1 RAs for use in individuals without diabetes."

In an accompanying editorial "Spending Money, Saving Money We Don't Got: The Cost of Obesity," James A. Stone, MD, PhD, FRCPC, Clinical Professor of Medicine, Cumming School of Medicine, University of Calgary, says, "Cardiovascular specialists, and practically speaking, most clinicians and healthcare decision makers, have a limited knowledge of health economics. The nuances and the finer details of health economics with respect to cost-effectiveness, incremental cost-effectiveness ratios, cost-utility, quality-adjusted life years, cost-benefit analysis, productivity, efficiency, and effectiveness are mostly a black hole to be safely skirted around. Spending money on disease prevention is an investment in the long-term value of a population’s health, in contradistinction to the rather short-term value of an individual’s disease care."

Ana P. Johnson, PhD, Professor, Department of Health Sciences, Queen’s University, and co-author of the editorial, adds, "It can be exceedingly difficult to change the healthcare payer’s perspective with regard to investing in disease prevention, rather than disease treatment, when the return on the dollars invested, through adverse event reductions, may not accrue for decades."

Dr. Chew concludes, "Now that there is emerging high-quality evidence for semaglutide and its positive impact on weight loss and associated cardiovascular outcomes in individuals without diabetes, its cost-effectiveness and potential funding by healthcare insurance should be reconsidered. Our model is generalizable across Canada, and while healthcare-associated costs vary in different countries, our model and assumptions could be broadly applied to many jurisdictions."

 

---

Journal

Canadian Journal of Cardiology

DOI

10.1016/j.cjca.2024.09.025 

Method of Research

Data/statistical analysis

Ozempic, GPL-1s may help curb substance use disorders

 

, UTEP study finds

Peer-Reviewed Publication

University of Texas at El Paso

FacebookXLinkedInWeChatBlueskyMessageWhatsAppEmail

EL PASO, Texas (June 8, 2026) – A new study led by researchers at The University of Texas at El Paso found that use of weight loss drugs like Ozempic and other GLP-1s is associated with a lower risk of developing alcohol, opioid, nicotine and cocaine use disorders.

The study, led by UTEP School of Pharmacy researchers Tadesse Abegaz, Ph.D., and Gabriel Frietze, Ph.D., was published in Frontiers in Psychiatry. It looked at more than 142,000 cases of patients with type 2 diabetes or obesity, of which around 20,000 were prescribed GLP-1 medications. They then examined whether GLP-1 users were more or less likely to develop substance use disorders than similar counterparts who were not on the medications.

GLP-1s are a class of medications that were originally developed for treating obesity and diabetes. But emerging evidence suggests these medications may influence dopamine signaling and other neural pathways that contribute to cravings – not only of food but other substances.

"Our findings add to growing evidence that GLP-1 medications may influence more than appetite and blood sugar regulation," said lead author Abegaz. "These medications appear to affect brain pathways involved in reward and craving, which could help explain the lower rates of substance use disorders observed in our study."

The study found that people taking GLP-1 medications had:

• 74% lower odds of alcohol use disorder
• 69% lower odds of opioid use disorder
• 68% lower odds of nicotine use disorder
• 75% lower odds of cocaine use disorder

The team emphasizes that their findings do not establish cause and effect — GLP-1s do not specifically prevent patients from abusing substances. 

“We do not support prescribing these medications for addiction treatment at this time, Frietze said. “Because this was an observational study in a specific clinical population, randomized clinical trials are needed before GLP-1 medications can be recommended for treating addiction.”

However, the team believes their results are promising and plan to continue studying GLP-1s’ effect on substance abuse. 

“Our next goal is to conduct prospective research that follows individuals initiating GLP-1 therapy over time,” Abegaz said. “We aim to evaluate whether changes in the substance use behaviors occur after treatment begins and whether these changes related to improvements in mental health and quality of life. 

He added, “Ultimately, this work will help inform whether GLP-1 medications could become part of future treatment strategies for substance use disorders.”

Patient data for this study was provided by the National Institutes of Health All of Us Research program, one of the nation’s largest and most diverse health databases. 

---

Journal

Frontiers in Psychiatry

DOI

10.3389/fpsyt.2026.1766770 

New GLP-1 oral pill lowers blood sugar and reduces bodyweight

In a randomized clinical trial, Mass General Brigham researchers and global collaborators found positive results for people with type 2 diabetes

Peer-Reviewed Publication

Mass General Brigham

FacebookXLinkedInWeChatBlueskyMessageWhatsAppEmail

Oral GLP-1 medications have the potential to increase access to therapies that can help lower blood sugar and reduce bodyweight. Today, at the American Diabetes Association’s Scientific Session, Mass General Brigham physician investigator Vanita Aroda, MD, presented findings from SOLSTICE, a phase 2b randomized, placebo-controlled clinical trial that tested the oral GLP-1 RA known as elecoglipron. Results, which are published simultaneously in The Lancet, show that the drug significantly reduced blood glucose and bodyweight among people with type 2 diabetes, paving the way for oral formulations to help bridge current gaps in type 2 diabetes treatment.

“Our study’s findings underscore the expanding potential of oral GLP-1 receptor agonists for people with type 2 diabetes,” said Aroda, who is the Director of Diabetes Clinical Research in the Division of Endocrinology, Diabetes & Hypertension in the Mass General Brigham Department of Medicine. “To date, GLP-1 therapies have largely been limited to injectable or oral peptide formulations, each with inherent delivery and dosing constraints. Rigorous clinical trials like SOLSTICE can help us evaluate oral medications that may be just as effective for patients with diabetes while overcoming these limitations.”

Elecoglipron, the oral medication tested in the SOLSTICE clinical trial, has been developed for treating type 2 diabetes. Most available GLP-1 medications need to be administered via subcutaneous injection. Semaglutide, which is approved for type 2 diabetes, can be taken in pill form but must be taken on an empty stomach first thing in the morning, with food and water restricted for 30 minutes after. One GLP-1 oral non-peptide medication, orforglipron, has been approved in the U.S. for weight management.

SOLSTICE, which was sponsored by AstraZeneca, was conducted across nine countries, including the U.S. The study enrolled 406 participants with type 2 diabetes who were randomly assigned to treatment groups. The trial tested different starting doses, dose-escalation schemes, and maintenance doses.

The researchers found that, at all dose concentrations, the medication reduced glucose levels significantly more than the placebo arm after 26 weeks. Up to 89.6% of participants who took the medication achieved an HbA1c level of 7%—the standard target goal for average blood glucose levels over the past two to three months for most adults with diabetes. That’s compared to 24.9% of people who received placebo. Up to 72.3% of participants in the treatment groups achieved at least 5% weight reduction compared to 20.2% in the placebo group. Safety and tolerability were similar to other GLP-1 medications at this stage of development.

Aroda is also the principal investigator of REIMAGINE 1, a randomized controlled trial that evaluated CagriSema, a novel combination therapy that combines the amylin receptor agonist cagrilintide with the injectable form of semaglutide. Those results, presented at the ADA meeting and published in The Lancet Diabetes and Endocrinology, were also positive, with up to 87% of participants reaching the target HbA1c level of 7%.

“At the center of every one of our clinical trials is the goal of improving outcomes for patients,” said Aroda. “The studies being presented at this year’s meeting highlight how essential carefully designed trials are for evaluating new therapies, refining existing approaches, and ensuring that advances in science translate into safer, more effective care for people living with diabetes.”

Authorship: In addition to Aroda, authors include Melanie J Davies, Jill Maaske, Marcus Millegård, Víctor López Juan, Jens Aberle, Andreea Ciudin, Rory J McCrimmon, Olof Eklund, Judy L Shih, Mikaela Sjostrand, Donna Zarzuela, and Julio Rosenstock.

Disclosures: Aroda declares institutional contracts from Amgen, Applied Therapeutics, AstraZeneca, Biomea, Boehringer Ingelheim, Corcept, Eli Lilly, Fractyl, Kailera, Novo Nordisk, Pfizer, Recordati, Rhythm and Servier; and consulting fees from Baim Institute for Clinical Research, Mediflix, Sanofi, and Roche. Additional author disclosures can be found in The Lancet.

Funding: AstraZeneca.

Paper cited: Aroda VR et al. “Elecoglipron, an oral small molecule GLP-1 receptor agonist in adults with type 2 diabetes (SOLSTICE): a phase 2b, multicentre, randomised, placebo-controlled trial” The Lancet DOI: 10.1016/S0140-6736(26)00802-0

Available evidence limited but does not suggest major adverse outcomes with early GLP-1 use in pregnancy

Abstract: https://www.acpjournals.org/doi/10.7326/ANNALS-25-04820

Summary for Patients: https://www.acpjournals.org/doi/10.7326/ANNALS-25-04820-PS

URL goes live when the embargo lifts             

A target trial emulation estimated the risks associated with glucagon-like peptide-1 receptor agonist (GLP-1RA) exposure in early pregnancy. The findings did not indicate substantially increased risk for nonlive birth, abnormal fetal growth, or major congenital malformation with continuation of GLP-1RAs into the first trimester. As GLP-1RA use among women of reproductive age becomes more prevalent, the findings can provide some reassurance for pregnant women with unintentional first-trimester exposure to GLP-1RAs. The study is published in Annals of Internal Medicine. 

 

Researchers from Harvard T.H. Chan School of Public Health and colleagues analyzed insurance claims data from 3,572 pregnancies between 2011 and 2024, comparing continuation of GLP-1RAs into the first trimester (≥ 1 further dispensation after conception) relative to non-continuation. The findings showed similar risks between the two treatment regimens for most outcomes, with no definitive increase apparent for continued medication use. However, because estimates were imprecise, particularly for rarer outcomes of major congenital malformation and small size for gestational age at birth, the authors conclude that further research would be valuable to better understand safety of GLP1-RAs in pregnancy.

 

A widely used class of blood pressure medications may be associated with poorer kidney outcomes

 

 New research presented at the 63rd ERA Congress suggests that a widely used class of blood pressure medications may be associated with poorer kidney outcomes in people with type 2 diabetes (T2D), even among patients already receiving modern kidney-protective treatments.1

Dihydropyridine calcium-channel blockers (DCCBs) are a commonly prescribed class of blood pressure medications that work by relaxing blood vessels and are frequently used as second-line therapies in people with diabetic kidney disease (DKD). Researchers found that patients taking DCCBs alongside standard therapies had a significantly higher risk of major adverse kidney events, compared with those receiving alternative blood pressure treatments.

DKD is one of the leading causes of kidney failure worldwide.2 It develops when persistently high blood sugar damages the small blood vessels in the kidneys, gradually reducing their ability to filter waste from the blood. Controlling blood pressure is a cornerstone of treatment, as high blood pressure accelerates this damage.

In recent years, two classes of medication have transformed care for people with DKD: renin-angiotensin system (RAS) inhibitors, which lower blood pressure and reduce pressure within the kidney’s filtering units, and sodium-glucose cotransporter-2 (SGLT2) inhibitors, originally developed as diabetes drugs but now recognised for their kidney-protective effects and ability to reduce the risk of kidney failure. Together, these therapies now form part of the standard of care for most patients with DKD.

The study analysed data from 31,031 adults with T2D between 2016 and 2021. All patients were receiving both RAS and SGLT2 inhibitors as part of their care. Among the participants, 12,172 (39.2%) were also taking DCCBs, while 18,859 (60%) were receiving other antihypertensive treatments. Patients were followed for a median of approximately 3.5 years.

After adjusting for differences in baseline clinical and demographic characteristics, researchers found that DCCB use was associated with a 33% higher risk of a major adverse kidney event (R 1.33, 95%, CI 1.03-1.73). These events were defined as either a substantial decline in kidney filtration capacity – a drop of 40% or more in estimated glomerular filtration rate (eGFR), the standard measure of kidney function – or progression to end-stage kidney disease requiring dialysis or transplantation.

"DCCBs are widely used as second-line blood pressure treatments in patients with DKD," said Dr Timna Agur, lead author of the study. "Our findings raise important questions about whether these medications are always the best option for patients already receiving modern kidney-protective therapies."

The researchers believe the findings may be explained by the way DCCBs affect blood flow within the kidney. In DKD, the kidneys are already exposed to increased pressure and hyperfiltration, a state in which the filtering units are working under excessive strain. Researchers suggest DCCBs may preferentially relax the blood vessels carrying blood into the kidney’s filtering units without having the same effect on vessels carrying blood out, potentially increasing pressure within these structures and contributing to ongoing kidney damage.

"We initially thought the kidney-protective effects of SGLT2 inhibitors might counterbalance the potential harms associated with DCCBs," said Dr Agur. "However, the increased risk of kidney disease progression appeared to persist even in this group."

The researchers caution that the study was observational in nature and cannot establish direct causation. Nevertheless, they argue the results are clinically significant given how commonly DCCBs are prescribed in this patient population.

“Further prospective studies and randomised controlled trials are needed to confirm these observations and better define the safest blood pressure treatment strategies for patients with DKD”, concluded Dr Agur. “However, given how commonly these medications are prescribed, any increase in kidney risk could have important implications for large numbers of patients with DKD.”

Semaglutide linked to better quality of life in diabetes and kidney disease

 

, FLOW trial shows

New findings from the landmark FLOW trial, presented at the 63rd ERA Congress, show that once-weekly semaglutide significantly improved health-related quality of life in adults with type 2 diabetes (T2D) and chronic kidney disease (CKD)

Reports and Proceedings

Beyond

FacebookXLinkedInWeChatBlueskyMessageWhatsAppEmail

(Glasgow, Scotland) New findings from the landmark FLOW trial, presented at the 63rd ERA Congress, show that once-weekly semaglutide significantly improved health-related quality of life in adults with type 2 diabetes (T2D) and chronic kidney disease (CKD), equivalent to around eight additional days in full health per year.1

The trial previously demonstrated that semaglutide reduced the risk of major kidney disease events by 24% and all-cause mortality by 20% compared with placebo over a median treatment duration of 3.4 years.² This new analysis provides complementary patient-centred evidence, showing that the benefits of semaglutide may extend beyond traditional clinical outcomes to how patients feel and function in everyday life.

For people living with both T2D and CKD, symptoms, treatment burden and reduced physical functioning can substantially affect day-to-day well-being, making quality of life an increasingly important treatment goal.

Among 3,533 randomised participants in the FLOW trial, 1,767 received semaglutide and 1,766 received placebo. Health-related quality of life (QoL) was assessed using the EQ-5D-5L questionnaire, a patient-reported measure of health status and well-being covering mobility, self-care, usual activities, pain/discomfort, anxiety/depression, and overall health perception. Participants completed the questionnaire at baseline and yearly thereafter.

After two years of treatment, health utility scores – which range from 0 (equivalent to death) to 1 (perfect health) – remained stable in the semaglutide group but declined in those receiving placebo. The estimated treatment difference of +0.021 (p=0.0001) corresponded to approximately eight additional days per year spent in full health.

Self-rated general health scores, measured using a visual analogue scale, also improved with semaglutide but worsened with placebo, with a significant treatment difference of +2.15 (p<0.0001), again becoming worse over time with placebo while stable on semaglutide.

Four of the five areas assessed by the EQ-5D-5L questionnaire (mobility, self-care, usual activities, and pain/discomfort) improved significantly with semaglutide compared with placebo (all p<0.03). No significant difference was observed in anxiety/depression (p=0.55). Benefits were broadly consistent across patient subgroups, including age, BMI, kidney function, urine albumin-to-creatinine ratio and previous cardiovascular events.

“We were surprised by the extent of the quality-of-life benefits seen with semaglutide, because they were not only clinically meaningful but consistently experienced across multiple aspects of daily life, including physical functioning and overall well-being,” said Professor Johannes Mann, lead author of the study.

“We were uncertain about quality-of-life outcomes because gastrointestinal side effects are common with GLP-1 receptor agonists,” Prof. Mann explained. “Our findings, however, confirm that the benefits of semaglutide in chronic kidney disease extend beyond traditional clinical endpoints to subjective outcomes that matter directly to patients.”

Globally, over 850 million people are living with CKD, and cases have more than doubled since 1990.3 It is a long-term condition in which there are abnormalities in kidney structure or function for at least three months with an impact on health, and is closely associated with diabetes, hypertension and cardio-kidney-metabolic conditions.4,5 CKD increases the risk of kidney failure and premature death, making early detection vital to enable timely interventions that may help slow disease progression.6

The findings may also influence how clinicians discuss treatment goals with patients living with T2D and CKD.

“When speaking with representatives of CKD patient groups and in discussions around clinical trial outcomes, patients often place considerable importance on quality of life alongside longevity,” said Prof. Mann. “Our findings reinforce the importance of a broader, patient-centred approach to treatment goals. They suggest that, overall, well-being may improve with semaglutide despite gastrointestinal side effects, complementing previously reported reductions in kidney and mortality risks.”

A key next step for researchers will be to better understand what specifically drives the quality-of-life improvements observed with semaglutide and the mechanisms underlying these effects.