Latest news with #GLP1Agonists
Daily Mail
7 days ago
- Health
- Daily Mail
Ozempic found to slash risk of disease affecting 6.7m Americans each year
Blockbuster weight loss drugs could slash the risk of developing memory-robbing dementia, a major study suggests. Researchers in Ireland analyzed clinical trials of nearly 165,000 taking drugs to lower their glucose (blood sugar) and treat diabetes. The team found most glucose-lowering treatments had no significant impact on dementia risk. However, people taking GLP-1 agonists like Ozempic and Wegovy were 45 percent less likely to develop dementia at some point in their lives than people on other drugs. While it's unclear exactly how the active ingredients in these drugs - most often semaglutide and tirzepatide - reduce the likelihood of dementia, the researchers believe they may lower inflammation in the brain. Neuroinflammation is thought to damage neurons and disrupt communications to part of the brain responsible for memory, triggering dementia symptoms. GLP-1 agonists may also reduce toxic amyloid and tau proteins, hallmarks of dementia. The team suspects GLP-1 agonists like Ozempic may help prevent both diabetes and dementia, both of which are on the rise in the US. Dr Catriona Reddin, senior study author and researcher at the University of Galway, said: 'This research represents a significant contribution to our understanding of how some diabetes medications may impact brain health. 'Diabetes is a known risk factor for dementia, but whether glucose-lowering therapies can help prevent cognitive decline has remained unclear. 'Our findings suggest that GLP-1 receptor agonists, in particular, may have a protective effect on brain health.' The study comes after a similar experiment from the University of Florida, which tracked 400,000 Americans on glucose-lowering drugs and found dementia risk was 33 percent lower for GLP-1 users compared to other interventions. Around 8million adults in the US have some form of dementia, and 500,000 are diagnosed every year. Meanwhile, one in eight US adults has reported taking Ozempic or similar medications at least once for diabetes or weight loss. In the new study, published in JAMA Neurology, researchers identified 26 studies that explored the relationship between GLP-1 agonist use and dementia. These included a total of 164,531 participants, most of whom (65 percent) were men. The average age was 64 with a follow-up time of 31 months. Studies included in the analysis were published between 2015 and 2024. Of the 26 in the review, 10 looked at the impact of GLP-1 agonists. The team suspected GLP-1 agonists may lower inflammation, which is a major driver of dementia. It's thought to activate the immune cells microglia and astrocytes in the brain, which damage neurons and disrupt the blood-brain barrier, the brain's protective layer. GLP-1 agonists have also been shown to lower blood pressure and protect blood vessels, reducing the risk of vascular dementia. A study published in April also found GLP-1s may stimulate neural growth in the hippocampus, an area of the brain responsible for learning and memory formation. However, this research is early. Professor Martin O'Donnell, Dean of the College of Medicine, Nursing and Health Sciences at University of Galway: 'Given the increasing prevalence of both diabetes and dementia, findings from this study have important public health implications for prevention of dementia.' Recent reports from the Alzheimer's Association report rates of Alzheimer's disease - the most common form of dementia - have risen 25 years in a row in the US. Diabetes, meanwhile, affects 12 percent of Americans - 38million. Reports published in 2022 suggest rates in the Americas have tripled in the last 30 years. There were several limitations to the new study, mainly including a lack of data on subtypes of dementia like vascular and Lewy body dementia.
Yahoo
14-07-2025
- Business
- Yahoo
Market to Reach $14.34 Billion by 2034, Driven by Innovative R&D, Strategic Collaborations, and Drug Formulation Advancements
The Europe GLP-1 agonists market, valued at USD 7.09 billion in 2024, is set to grow at a 17.30% CAGR, reaching USD 14.34 billion by 2034. Driven by rising diabetes and obesity rates, innovative drug formulations, and supportive healthcare policies, the market is expanding. Key players include Eli Lilly, Sanofi, and Novo Nordisk. Challenges involve high costs and regulatory complexities. Opportunities lie in obesity treatment expansion and advanced drug delivery systems. European Glucagon-like Peptide-1 (GLP-1) Agonists Market Dublin, July 14, 2025 (GLOBE NEWSWIRE) -- The "Europe Glucagon-like Peptide-1 (GLP-1) Agonists Market Report and Forecast 2025-2034" has been added to offering. The Europe glucagon-like peptide-1 (GLP-1) agonists market is projected to witness significant growth, fueled primarily by an increased prevalence of type 2 diabetes and obesity. Originally valued at USD 7.09 billion in 2024, the market is estimated to expand at a compound annual growth rate (CAGR) of 17.30%, expecting a valuation of USD 14.34 billion by 2034. The competitive landscape features major pharmaceutical firms like Novo Nordisk, Eli Lilly, Sanofi, AstraZeneca, and others focused on innovative R&D, strategic collaborations, and drug formulation advancements. These companies aim to enhance market presence through mergers, acquisitions, and partnerships that promote access and compliance, ensuring sustained growth in the Europe's GLP-1 agonists market. The market's expansion is propelled by the increasing incidence of diabetes and obesity, augmented by sedentary lifestyles and poor dietary choices. GLP-1 agonists, as incretin-based therapies, are preferred for their efficacy in controlling blood sugar levels and facilitating weight loss, crucial aspects in managing diabetes and obesity. The growth trajectory is supported by rising healthcare expenditure, a burgeoning elderly demographic, advancements in drug delivery, and a robust regulatory framework favoring novel therapeutic adoption. Key Attributes: Report Attribute Details No. of Pages 300 Forecast Period 2025 - 2034 Estimated Market Value (USD) in 2025 $7.09 Billion Forecasted Market Value (USD) by 2034 $14.34 Billion Compound Annual Growth Rate 7.3% Regions Covered Europe Market Drivers A surge in type 2 diabetes and obesity cases. Favorable government initiatives and reimbursement policies bolstering access to innovative treatments. Improved drug formulations like once-weekly injectables and oral options enhancing patient compliance. A growing trend towards combination therapies integrating GLP-1 agonists for optimized results. Market Challenges High costs of GLP-1 therapies affecting widespread accessibility. Potential side effects that could hinder patient adherence. Regulatory complexities delaying new therapy commercializations. Future Opportunities Expanding applications in obesity treatment beyond diabetes management. Innovative drug delivery system developments heightening market penetration. Strategic R&D investments for next-gen GLP-1 therapies with enhanced efficacy. Europe GLP-1 Agonists Market Trends The shift towards long-acting GLP-1 formulations like once-weekly injections elevating patient compliance. The increasing use of GLP-1 agonists in obesity management, supported by regulatory endorsements. Clinical validation of cardiovascular benefits driving GLP-1 adoption among patients at cardiovascular risk. Policymaker efforts in expanding healthcare coverage improving treatment accessibility. The development of multi-target GLP-1 therapies promises superior management of diabetes and weight issues. Strategic collaborations in biosimilar production broadening market access and affordability. Market Segmentation By Drugs: Key drugs include dulaglutide, exenatide, liraglutide, tirzepatide, lixisenatide, and semaglutide. By Application: The applications span type 2 diabetes mellitus and obesity treatment. By Route of Administration: Dominated by parenteral routes, the market is gradually seeing a rise in oral solution adoption. By End User: Primary users are hospitals, specialty clinics, academic research sites, with home care settings gaining traction. By Distribution Channel: Hospital pharmacies prevail, while retail and online pharmacies steadily gain ground. By Region: The United Kingdom, Germany, France, and Italy emerge as principal markets, bolstered by strong infrastructure and supportive policies. Companies Featured Eli Lilly and Company Sanofi Novo Nordisk A/S AstraZeneca plc For more information about this report visit About is the world's leading source for international market research reports and market data. We provide you with the latest data on international and regional markets, key industries, the top companies, new products and the latest trends. Attachment European Glucagon-like Peptide-1 (GLP-1) Agonists Market CONTACT: CONTACT: Laura Wood,Senior Press Manager press@ For E.S.T Office Hours Call 1-917-300-0470 For U.S./ CAN Toll Free Call 1-800-526-8630 For GMT Office Hours Call +353-1-416-8900Sign in to access your portfolio
Medscape
09-05-2025
- Health
- Medscape
May 09 2025 This Week in Cardiology
Please note that the text below is not a full transcript and has not been copyedited. For more insight and commentary on these stories, subscribe to the This Week in Cardiology podcast , download the Medscape app or subscribe on Apple Podcasts, Spotify, or your preferred podcast provider. This podcast is intended for healthcare professionals only. In This Week's Podcast For the week ending May 9, 2025, John Mandrola, MD, comments on the following topics: the controversial KETO-CTA study, tough decisions in subclinical AF, and potentially huge benefit for GLP-1 receptor agonists. Meta-analysis The journal JACC Advances published a study looking at plaque progression in people eating a ketogenic diet (KD). It stirred all sorts of controversy on social media. I will review it this week. A few background comments. An obstacle to the broad clinical implementation of carbohydrate-restricted diets (CRDs) and KD are lipid changes that occur in a minority of patients upon carbohydrate restriction. Bad lipid changes. As in large increases in LDL cholesterol (LDL-C) and associated apolipoprotein B (ApoB). While there are many factors contributing to increases in LDL-C and ApoB in the KD, "leanness" seems important. Get this: The authors cite a meta-analysis of 41 studies that reports that mean baseline BMI had a strong inverse association with LDL cholesterol change [whereas saturated fat amount was not significantly associated with LDL-C change. For trials with mean baseline BMI <25, LDL cholesterol increased by 41 mg/dL (95% CI, 19.6-63.3) on the low carbohydrate diet (LCD). By contrast, for trials with a mean of BMI 25 to less than 35, LDL cholesterol did not change, and for trials with a mean BMI ≥35, LDL cholesterol decreased by 7 mg/dL (95% CI, –12.1 to –1.3). I did not know that lipid changes with CHD was modified by BMI. These observations have given rise to the characterization of the lean mass hyper-responder (LMHR) phenotype. From the authors: the aim of the study was "to examine the association between plaque progression and its predicting factors." I know; it is a bit confusing. 100 people who were on a KD (for years actually), and had a "keto-induced" LDL-C ≥190 mg/dl and HDL ≥60 mg/dl and TG ≤ 80 mg/dl were followed for 1 year using coronary artery calcium (CAC) scan and coronary computed tomography angiography (CCTA). I say "keto-induced" because the LDL-C had to be less than 160 before adapting the KD. Entry criteria also included an increase in ≥ 50% in the LDL-C. Plaque progression predictors were assessed with linear regression and Bayes Factors. Study subjects had to have normal glucose and A1c and normal CRP. Patients on the KD had a normal BMI at 22 and very high LDL of 254, HDL 89 and triglycerides of 67. Pause there: average LDL 254, so many were higher. These were 55-year-old mostly men who were adherent to KD as documented with beta-hydroxybutyrate (BHB) measures. Over the year, there was no substantial changes in ApoB or BMI. The study was actually pre-registered, and the primary endpoint was originally the change in noncalcified plaque burden. They did not formally present this endpoint. Instead, they gave the median change in percent atheroma volume, which they said was 0.8%. Who knows what this means? They tells us that this value is comparable with those observed in other cohorts. The thing is…the primary endpoint of change in noncalcified plaque volume (NCPV) was presented in a figure which you could look at and see that most individuals have an increase in NCPV. This lack of data on the PEP caused a stir online and the lead author offered the data in a video on Twitter/X. The numerical pooled NCPV change value was an in increase of 18.8 mm³. If this means nothing to you, don't worry. I will come back to it. Weird though that we had to get the primary endpoint in a Twitter video. The main thrust of the paper were the correlations. Neither the change in ApoB throughout the study nor the ApoB at the beginning of the study were associated with the change in NCPV. There was also no correlation between LDL-C and NCPV. What was correlated? The baseline CAC was positively associated with a change in NCPV. So also were baseline plaque measures. Simplifying: if there was plaque or CAC at baseline, there was a positive correlation with NCPV. The authors make the case that while both LDL-C and ApoB are independent risk factors for atherosclerosis, the absolute risk associated with elevated LDL-C and ApoB is context-dependent and may not apply to this lean mass hyper-responder (LMHR) group. Thus, they write, "these data are consistent with the observation that high LDL-C and ApoB among a metabolically healthy population have different cardiovascular risk implications than high LDL-C among those with metabolic dysfunction." Gosh, that is a big conclusion because these people had total cholesterol of 350 and LDL-C of 255. The authors make the case that the lean mass hyper-responders are different from the person with abnormal lipids from metabolic syndrome: Difference 1 : LDL-C and ApoB elevations are dynamic and result from the metabolic response of carb restriction and this is not a genetic defect. Difference 2 : LMHR are normal weight and metabolically healthy; they don't have obesity, diabetes, or insulin resistance. Difference 3 : The high LDL-C and ApoB in this phenotype emerge as part of a lipid triad, also inclusive of high HDL-C and low triglycerides, representing a metabolic signature of a distinct physiological state. Difference 4: The degree of this phenotype appears inversely related to BMI ("leanness"), consistent with the idea that it is a metabolic response to carbohydrate restriction that is accentuated in leaner, more metabolically healthy persons. The authors really are not shy in their conclusions. And I call them Whoppers No. 1, No. 2, and No. 3: Whopper 1: The LMHR population constitutes a unique and important natural experiment evaluating the lipid heart hypothesis in an unprecedented manner. Whopper 2: Our data are consistent with the notion that elevated ApoB, even at extreme levels, does not drive atherosclerosis in a dose-dependent manner in this population of metabolically healthy individuals. They qualify this conclusion by saying that LHMR may still have risk. For instance, they noted that PAV increase comparable to what has been observed in other studies on populations with lower LDL-C across the cardiovascular disease risk spectrum. They offer no citation here. Whopper 3: Quote: "These insights can facilitate personalized treatment and risk mitigation strategies based on modern, cost-effective cardiac imaging." For instance, they say, despite profound elevations in LDL-C and ApoB, based on their data, LMHR subjects with CAC = 0 at baseline (n = 57) constitute a low-risk group for percent atheroma volume (PAV) progression, even as compared to other cohorts with far lower LDL-C and ApoB. By contrast, LMHR subjects with elevated baseline CAC, possibly from a history of metabolic damage and dysfunction prior to adopting a CRD, appear to constitute a relatively higher risk group for PAV progression even where LDL-C and ApoB are equal to their CAC = 0 counterparts. Before closing they coin the phrase " plaque begets plaque. " I see why this paper generated angst online. The idea of the study is reasonable; what's unreasonable are the conclusions. First, if you look at the primary endpoint of change in noncalcified plaque volume, it went up. A lot. 18.8 mm3. That was 2.5x higher than they predicted in their study protocol. So, if you believe that the delta of NCPV is a great surrogate, it looks quite ominous. Second, imaging tests are almost always a terrible surrogate measure. Images are images. To assess risk, you need to measure events. Heart attacks. Stroke. CV death. I realize this is a small uncontrolled study, and it's fine to look at these things (in fact, I am curious), but you cannot claim clinical importance just because you weaved a nice story about high LDL-C in LMHR being different from high LDL-C in metabolic syndrome patients. Third, there is like 50 years of data supporting LDL-C being causal for atherosclerosis. Like every Bradford Hill criteria is met. So…. If you are going to claim an exception, you need more rigorous evidence than this. The priors here — the priors being that these LMHR are an exception — have to be extremely pessimistic, so you'd need really strong data to change your posterior view. This study surely was not strong evidence. Fourth, assuming you believe the plaque images are precise and reproducible and clinically relevant, this study really suffers from a lack of control. All they had to do is recruit a group of people eating a Mediterranean diet. Let's see what happens to them relative to the Keto people. Fifth, the authors don't tell us how many people they screened to find these 100 people. I get the sense they are highly selected bunch. Finally, the question of heart health from a specific diet is going to be really hard to sort out. Nutritional studies always are. An RCT in a prison might work, but cardiac event rates in young people—even with KD-induced LDL will be infrequent. What's more, the LMHR will surely do other things that affect heart disease, like exercise, not smoking etc. If the authors are wrong, and actually eating a diet that causes crazy high LDL levels and maintaining a lean body mass is actually harmful , then, given the popularity of carbohydrate-restricted diets, this could be a public health disaster. As for diet, I do think Americans eat too many carbs, but the KD seems extreme. Why not just eat a balanced diet, like they do in Sicily? JAMA Network Open has published an interesting modeling study from a Finnish group on the matter of net benefit of oral anticoagulation (OAC) in subclinical device-detected atrial fibrillation (AF). The background here is known to anyone practicing cardiology. It's perhaps the most common question I receive: John, Mrs Smith had 4 hours of AF on her pacemaker. Her CHA 2 DS 2 VASc score is 4; should we anticoagulate? And if we don't anticoagulate, how much AF does she have to have before we do? The short answer is that I have no idea. Your comeback is…come on Mandrola, we have two trials. And it is true. We have the NOAH trial. Edoxaban vs placebo in 2500 patients with a median duration of AF 2.8 hours. The primary outcome of CV death, stroke, and systemic embolism (SE) was 19% lower in the edoxaban group. The confidence intervals (CI) were wide, and the difference did not reach significance. Major bleeding was 31% higher and this did reach statistical significance. We also have the ARTESIA trial. Apixaban vs acetylsalicylic acid (ASA) in 4000 patients with median duration AF 1.5 hours. The primary outcome of stroke and SE was 37% lower with apixaban and this did meet statistical significance. Major bleeding however was 80% higher and this met statistical significance. Some have said NOAH was negative and ARTESIA was positive. Perhaps, technically, this is true. But I think they both show the same thing. OAC reduces stroke and increases bleeding. It leaves us with the question of net benefit. I've heard Jeff Healey, the PI of ARTESIA, rightly say that we should favor OAC because strokes are worse than bleeds. This is certainly true. The tension in subclinical AF is that the yearly stroke rates were low—in the 1% range. Far lower than what would be predicted in the CHA 2 DS 2 VASc assessment for clinical AF. And if that is true, even if OAC reduces the relative risk, the absolute risk reduction is tiny, in the order of 4 per 1000, with a number needed to treat (NNT) of 250. Therefore, any increase in bleeding may mitigate the net benefit. Led by senior author Konsta Teppo, the group set out to estimate the "net benefit" of OAC in SCAF. They used modeling. It's technical. A Medscape colleague, nephrologist F. Perry Wilson, covered this paper, and he wrote: The study was done using a computer. I know — all studies are done with computers. But here I mean literally. The authors used a decision analytical model run with 10,000 patients with subclinical AF on OAC and 10,000 without OAC. They then used a "Markov decision model" to estimate net outcomes of NOACs. You all know that doctors who ablate AF and put in pacers and defibrillators don't know much about Markov modeling. I was going to ask Professor Teppo. He would have told me. But to make life easier, I just asked Claude. Who said: A Markov model consists of multiple health states individuals can move between based on specific transition probabilities. Think of it as a simulation where: Patients exist in various health states (e.g., well, post-stroke, bleeding event, death) In each cycle (1 month in this study), patients can transition between states with certain probabilities The model tracks what happens to a cohort of simulated patients over time The model was constructed in multiple steps: Base Case Patient: The researchers created a model patient, aged 77 years (matching the average age in the clinical trials), and applied the untreated stroke and bleeding rates from the NOAH-AFNET 6 and ARTESIA trials. Health States: The model included states for: Being Well with subclinical AF Ischemic stroke (with varying severities) Major bleeding events (hemorrhagic stroke, other intracranial bleeding, extracranial bleeding) Development of clinical AF Death Transition Probabilities: The pooled point risk estimates from the meta-analysis combining the two trials were used as the effect sizes for anticoagulation on stroke (32% decrease) and major bleeding (62% increase). The model assigned an 80% weight to nonintracranial bleedings for the increase in bleedings caused by the DOACs. The numbers come from the McIntyre et al meta-analysis of NOAH and ARTESIA in Circulation . Event Severity: Probabilities for the severity of stroke and bleeding events in the anticoagulation and non-anticoagulation groups of the model were approximated from previous observations in patients with and without anticoagulation. Quality of Life Weights: The net benefit outcome was assessed in terms of QALYs (Quality-Adjusted Life Years), where clinical events reduced patients' quality of life based on the type and severity of the event according to previously published quality of life data. Time Horizon: The simulation was run for a 10-year period with 10,000 samples in both decision groups (with and without the DOACs). The main outcome measure for net benefit was the cumulative quality-adjusted life-years (QALYs) during the simulation. This included things like severity of ischemic strokes, hemorrhagic strokes, other intracranial bleeds, and extracranial bleeds, as well as the number of deaths during a 10-year simulation. It's really neat way to look at net benefit. As I said, I don't know anything more than what I read about Markov modeling, but the thing that strikes me, and perhaps you too, is that there are a lot of degrees of freedom of choices. That said, here is what the model shows: Over the 10-year period, you would have 1076 strokes in nontreated subclinical AF vs 843 with treatment. The delta of 233 strokes saved seems like a lot but it's only 2.3% per year. There would be 1213 major bleeds without OAC vs 1664 with OAC. The 453 more bleeds that would be 4.5% per year. Deaths were nearly the same. 55 fewer in the anticoagulation (AC) arm but it's only 0.6% delta per year. OK, what about the primary endpoint of quality-adjusted life years. It was, drumroll… Per patient, the differences listed led to 1 additional quality-adjusted week of life (0.024 QALYs) with DOAC treatment during the 10-year simulation. When the 95% CIs of treatment effect sizes were considered in probabilistic sensitivity analysis, there was a 66% probability that DOAC treatment leads to more QALYs than withholding treatment. The authors did an exploratory analysis looking at higher risk patients and as you would expect, in patients with CHADSVASC score >4, the increase QALY with DOAC was now a month, not a week. But they note caution because this estimate came from subgroup analyses in the two trials, neither of which met statistical significance for interaction. The authors concluded that "initiating DOACs in patients with device-detected subclinical AF was associated with a minimal increase in QALYs. However, the benefits were uncertain, and the effect size of the overall net benefit does not appear to be clinically meaningful." I loved this paper and the authors' discussion. The modeling and estimates make intuitive sense, right? The trials find extremely low rates of stroke with SCAF. The average age of patients was 77. Older patients have many competing risks. Andrew Foy has a nice model thinking about domains acting on treatment effect. They are overlapping circles where you have the risk of the primary outcome vs competing risk, and the treatment benefit and treatment harm. Treating subclinical AF is a perfect example of these four domains coming together to almost cancel themselves out. The Markov model basically quantifies this to 1-week extra of good quality of life. Perhaps a few weeks longer if the patient has extremely high stroke risk. The clear conclusion I make from this paper is that subclinical AF is a different entity than clinical AF of old. I co-authored a paper on that in Stroke . The Finnish group has shown very little net benefit in treating SCAF. This contrasts with the famous Singer et al net benefit paper in Annals of Internal Medicine in 2010, where they showed clear net benefit of warfarin in patients in the ATRIA cohort. Here, even with an annual stroke rate of only 2%, warfarin provided a large net benefit. In clinical AF, stroke reduction for anticoagulation was larger than the bleeding increase. But subclinical AF has a different meaning. Yes, it is electrically the same; the atria is fibrillating. But, and this is my opinion, I am beginning to think that a certain degree of short duration occurs in older people as a matter of normal life. We know that PACs and PVCs increase with age, why not short duration AF? For now, the only solution to the matter is to do what David Sackett described when he coined the term evidence-based medicine. That is, we align care with patient preferences. With our patients we discuss the uncertainty, seek their preferences, and treat accordingly. There can be no algorithm, no guideline. This problem does not fit into those colored boxes in guidelines, and the top people who write guidelines should resist the urge to help us clinicians. If a patient fears stroke and is willing to deal with the disutility of taking a daily pill (that is, the cost and taking it every day), then use OAC. If a patient fears bleeding, then hold off and monitor more. I know, this is a cardiology podcast, but here me out. There is a connection. Plus, the science of this study is striking. In Kentucky, one of the least healthy states in the US, obesity is essentially the norm. I estimate that more than half the patients I see in clinic have some degree of metabolic syndrome—overweight or obese, insulin resistant, type 2 diabetes (T2D). Many of these patients also have fatty liver disease, which used to be called non-alcoholic steatohepatitis, or NASH. But it is now called MASH, or metabolic-associated steatohepatitis. It's a bad condition, and I think it flies under the radar of most of us cardiologists—because we see these patients for hypertension or AF or ischemic heart disease. My friend Claude says that 9-15 million adults in the US have MASH. And it's getting worse. The prevalence of MASH in the US is predicted to increase 63% from 16.5 million cases in 2015 to 27 million cases in 2030. And in patients with T2D and obesity, the prevalence of MASH is as high as 16%, so almost 1 in 5 patients. NEJM recently published the results of the ESSENCE trial of 1197 patients with documented inflammation on liver biopsy of semaglutide vs placebo. This is a two-part trial. Part 1 looks at histology. And it has resolution of steatohepatitis without worsening of liver fibrosis and reduction in liver fibrosis without worsening of steatohepatitis as the primary endpoints. ESSENCE trial is ongoing, and Part 2 will measure clinical outcomes. NEJM published the PART 1 and it is shocking. Patients were young, age 56, and more than half were females. The mean BMI was 34-35. The primary endpoints were twofold: Resolution of steatohepatitis without worsening of fibrosis occurred in 63% vs 34% in the semaglutide vs placebo groups. That is an absolute treatment difference of 29 percentage points, which was highly significant. The second primary endpoint, a reduction in liver fibrosis without worsening of steatohepatitis, was reported in 37% vs 22% in the semaglutide vs placebo arms. That is absolute treatment diff of 14.4 percentage points, also highly significant. All secondary outcomes favored semaglutide. I mention this study because a) oodles of our patients have MASH, whether we know it or not, b) MASH is on the rise, and c) MASH portends a poor prognosis; it is the leading cause of liver transplant, but perhaps most relevant to cardiologists is that most patients with MASH die of cardiovascular (CV) complications. The GLP-1 agonist drug in ESSENCE basically shredded evidence of liver disease, at least histologically, and I suspect the follow-on outcomes portion of ESSENCE will be stopped early for benefit. There is an approved medication for MASH, called resmetirom, but this is a thyroid hormone receptor-beta (THR-β) selective agonist that specifically targets the liver. Other than mild lipid-lowering effects, it has no known CV benefits. This is unlike GLP-1 agonists which have RCT-proven benefits in CV disease and diabetes. I am not yet prescribing GLP-1, but like the SGLT2 inhibitors, I think GLP-1 agonists will soon be a drug that cardiologist will want to prescribe. I realize that some listeners may say we should be treating obesity and obesity-related diseases with weight loss and diet and exercise. The GLP-1 benefit seen in ESSENCE was likely due to weight loss. My answer to that is it doesn't matter why the GLP-1 drugs work. When trials show that something works, an evidenced-based practitioner should embrace it. What's more, clinical medicine is pragmatic. It's pretty obvious that lifestyle interventions have a low success rate. So, if the GLP-1 agonists work, we should prescribe them. And, finally, there is a big difference in using GLP-1 agonists in an adult with diabetes, heart disease, and liver inflammation vs an adolescent who is overweight. The former person is in real trouble. The net benefit calculus favors treatment. The younger person should be counseled aggressively to change lifestyle. In other words, treatment is different from prevention. CABG Still Superior to Stents Despite FAME 3 Endpoint Swap A few weeks ago, I discussed the FAME-3 trial 5-year results. I turned this into a column that is up now. The short story is that FAME-3 was designed as a one-year non-inferiority trial comparing fractional flow reserve (FFR)-guided PCI to coronary artery bypass grafting (CABG) in patients with multivessel disease. Why someone would want to compare revascularization strategies at one year is mysterious, but that is what they did. And CABG was much better. FFR-PCI did not even reach non-inferiority in a four-point composite endpoint of death, myocardial infarction, stroke, and unplanned revascularization. My column pushes back against the claims in 3 and 5-year results that FFR-PCI is now equivalent to CABG. The claims stem from use of a different endpoint. Take a look at my column and see what you think.
