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  • Widely panned arsenic life paper gets retracted—15 years after brouhaha

    Widely panned arsenic life paper gets retracted—15 years after brouhaha

    In all, the astronomic hype was met with earth-shaking backlash in 2010 and 2011. In 2012, Science published two studies refuting the claim that GFAJ-1 incorporates arsenic atoms into its DNA. Outside scientists concluded that it is an arsenic-tolerant extremophile, but not a profoundly different life form.

    Retraction

    But now, in 2025, it is once again spurring controversy; on Thursday, Science announced that it is retracting the study once and for all.

    Some critics, such as Redfield, cheered the move. Others questioned the timing, noting that 15 years had passed, but only a few months have gone by since The New York Times published a profile of Wolfe-Simon, who is now returning to science after being seen as a pariah. Wolfe-Simon and most of her co-authors, meanwhile, continue to defend the original paper and protested the retraction.

    In a blog post Thursday, Science’s executive editor, Valda Vinson, and Editor-in-Chief Holden Thorp explained the retraction by saying that Science’s criteria for issuing a retraction have evolved since 2010. At the time, it was reserved for claims of misconduct or fraud but now can include serious flaws. Specifically, Vinson and Thorp referenced the criticism that the bacterium’s genetic material was not properly purified of background arsenic before it was analyzed. While emphasizing that there has been no suggestion of fraud or misconduct on the part of the authors, they wrote that “Science believes that the key conclusion of the paper is based on flawed data,” and it should therefore be retracted.

    Jonathan Eisen, an evolutionary biologist at UC Davis, criticized the move. Speaking with Science’s news team, which is independent from the journal’s research-publishing arm, Eisen said that despite being a critic of the 2010 paper, he thought the discussion of controversial studies should play out in the scientific literature and not rely on subjective decisions by editors.

    In an eLetter attached to the retraction notice, the authors dispute the retraction, too, saying, “While our work could have been written and discussed more carefully, we stand by the data as reported. These data were peer-reviewed, openly debated in the literature, and stimulated productive research.”

    One of the co-authors, Ariel Anbar, a geochemist at Arizona State University in Tempe, told Nature that the study had no mistakes but that the data could be interpreted in different ways. “You don’t retract because of a dispute about data interpretation,” he said. If that were the case, “you’d have to retract half the literature.”

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  • S&P 500, Nasdaq close at records; Deckers soars on UGG demand – Reuters

    1. S&P 500, Nasdaq close at records; Deckers soars on UGG demand  Reuters
    2. Markets News, July 25, 2025: S&P 500, Nasdaq Close Out Strong Week at Record Highs; Tesla Rebounds from Sell-Off, Intel Drops After Weak Earnings  Investopedia
    3. S&P 500 posts fifth straight record close this week, powered by solid earnings: Live updates  CNBC
    4. Alphabet and AI stocks nudge Wall Street to more records  apnews.com
    5. US stocks coast toward the finish of a record-setting week  Dunya News

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  • Genetic Study Finds Hypothyroidism May Increase PAH Risk

    Genetic Study Finds Hypothyroidism May Increase PAH Risk

    Hypothyroidism has been newly associated with greater risk of developing pulmonary arterial hypertension (PAH), in a study that used inverse variance weighting (IVW), MR-Egger regression (MR-Egger), and weighted median (WM) methods to reach this conclusion.1

    The research published in International Journal of Cardiology: Heart & Vasculature sought to connect 5 subtypes of thyroid dysfunction—free triiodothyronine (FT3), free thyroxine (FT4), thyrotropin (TSH), hypothyroidism, and hyperthyroidism—but found only hypothyroidism was connected to PAH. There was an approximately 49% greater risk of PAH in the presence of hypothyroidism (OR, 1.485; 95% CI, 1.051-2.100; P = .025).

    With hypothyroidism, the thyroid gland—which serves to regulate metabolism, growth, and development through hormone production—underdelivers; it is considered in an underactive state and can lead to bouts of fatigue and weight gain from a metabolism that has been greatly slowed.2 PAH is typically defined through right ventricular dysfunction, demonstrated by a mean pulmonary arterial pressure above 22 mm Hg,1 and symptom onset of dyspnea, syncope, lower extremity edema, abdominal distention, and angina.3

    This new study incorporated and evaluated summary data from the Genome-wide Association Studies (GWAS) of the European Ancestry Cohort for instrumental variables for thyroid dysfunction and PAH, and GWAS data on OAH were gleaned from the IEU OpenGWAS project. The authors evaluated single nucleotide polymorphisms (SNPs) for heterogeneity using Cochran’s Q test, ultimately selecting 30, 59, 161, 68, and 41 SNPs, respectively, for FT3, FT4, TSH, hypothyroidism, and hyperthyroidism.

    IVW produced the aforementioned 49% greater risk of PAH in the presence of hypothyroidism. MR-Egger (OR, 2.123; 95% CI, 1.011-4.459; P = .051) and the WM method (OR, 1.003; 95% CI, 0.578-1.739; P = .991) did not find similar associations, “but because the [β] values of each method were in the same direction (all greater than 0), we still consider that hypothyroidism can increase the risk of PAH,” the study authors noted. These β values were 0.753 for MR-Egger, 0.003 for the WM method, and 0.396 for IVW.

    In contrast, the β values for MR-Egger were negative for FT3, FT4, and TSH but positive for hyperthyroidism; for the WM method, negative for all; and for IVW, positive for FT3 and hyperthyroidism but negative for FT4 and TSH. Also, heterogeneity and horizontal pleiotropy were not seen among these findings (P > .05).

    PAH is typically defined through right ventricular dysfunction, demonstrated by a mean pulmonary arterial pressure above 22 mm Hg and symptom onset of dyspnea, syncope, lower extremity edema, abdominal distention, and angina. | Image Credit: Kiattisak-stock.adobe.com

    Drilling down, the following results were seen for heterogeneity using Cochran’s Q test:

    • FT3: MR-Egger, 31.553 (P = .293); IVW, 31.636 (P = .336)
    • FT4: MR-Egger, 51.351 (P = .539); IVW, 51.406 (P = .575)
    • TSH: MR-Egger, 170.939 (P = .245); IVW, 170.959 (P = .262)
    • Hypothyroidism: MR-Egger, 69.464 (P = .362); IVW, 70.662 (P = .356)
    • Hyperthyroidism: MR-Egger, 53.735 (P = .058); IVW, 53.760 (P = .072)

    These were the authors’ findings on horizontal pleiotropy:

    • FT3: 0.022 (P = .788)
    • FT4: –0.009 (P = .816)
    • TSH: –0.003 (P = .892)
    • Hypothyroidism: –0.042 (P = .297)
    • Hyperthyroidism: –0.010 (P = .07)

    They also did not find evidence of reverse causal association between PAH and thyroid dysfunction.

    “Thyroid dysfunction is often combined with various autoimmune abnormalities, which induce systemic vascular inflammation,” the study authors wrote. “In addition, hypothyroidism is strongly associated with venous thromboembolic events.”

    Strengths of their findings are that they reflect the results of previous studies—prospective and retrospective analyses—showing elevated rates of hypothyroidism in children with PAH4 and the presence of thyroid disease in patients with pulmonary hypertension, with the highest prevalence in the setting of PAH.5

    However, limitations were noted, too. Because their data were from a solely European population, the findings may not apply to other populations. Also, the data they used were summary data, so they could not account for the potential influence of medications to treat PAH that may have precipitated thyroid dysfunction.

    The authors underscore that further investigation is needed to validate their findings.

    References

    1. Pang G, Wang X, Zhao R, et al. Thyroid dysfunction and pulmonary arterial hypertension: a bidirectional mendelian randomization study. Int J Cardiol Heart Vasc. 2025:60:101747. doi:10.1016/j.ijcha.2025.101747
    2. Hypothyroidism (underactive thyroid). Cleveland Clinic. Accessed July 25, 2025. https://my.clevelandclinic.org/health/diseases/12120-hypothyroidism
    3. PAH diagnostic criteria. PAH Initiative. Accessed July 25, 2025. https://www.pahinitiative.com/hcp/pah-overview/diagnosing-pah-criteria
    4. Kwiatkowska J, Zuk M, Migdal A, et al. Children and adolescents with pulmonary arterial hypertension: baseline and follow-up data from the Polish registry of pulmonary hypertension (BNP-PL). J Clin Med. 2020;9(6):1717. doi:10.3390/jcm9061717
    5. Li JH, Safford RE, Aduen JF, Heckman MG, Crook JE, Burger CD. Pulmonary hypertension and thyroid disease. Chest. 2007;132(3):793-797. doi:10.1378/chest.07-0366

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  • AllergyAware E-Learning Training Program Boosts Anaphylaxis Preparedness in School Staff

    AllergyAware E-Learning Training Program Boosts Anaphylaxis Preparedness in School Staff

    The AllergyAware e-learning course effectively trained school personnel on anaphylaxis management, significantly improving their knowledge and confidence in using epinephrine auto-injectors, despite some technical and pacing issues reported by users. | Image Credit: Flex_Point_Security – stock.adobe.com

    The AllergyAware e-learning course had significant benefits in equipping school personnel with essential knowledge and skills for managing anaphylaxis, offering a readily available and scalable training solution, but future research is necessary to assess participants’ application of knowledge in real-world settings, according to a study published in Allergy, Asthma & Clinical Immunology.1

    Food allergies significantly increase a child’s risk of anaphylaxis, a life-threatening hypersensitive reaction causing swelling, itching, skin redness, hypotension, and airway constriction. These allergies also bring psychosocial burdens that necessitate daily management, often reducing a child’s quality of life and leading to food-related anxiety and stress, social stigma, and peer bullying. About 40% of children with food allergies experience anaphylaxis.

    The CDC created the “Voluntary Guidelines for Managing Food Allergies in Schools and Early Care and Education Programs” as the first national guidelines for school food allergy management.2 These guidelines aim to protect the physical and emotional health of students with food allergies by offering information and strategies that help schools reinforce federal laws and regulations. Similarly, Ontario, Canada, passed Sabrina’s Law, legislation that established legally required steps to keep children at risk of anaphylaxis safe at school.3

    Lawmakers have introduced various forms of legislation to involve school personnel in recognizing anaphylaxis symptoms and responding to emergencies.1 Many situations require using stock epinephrine auto-injectors (EAIs) for a quick response to a child’s allergic reaction. Certain school boards with established anaphylaxis prevention and management strategies have demonstrated the benefits of including proper training for school personnel when administering epinephrine, but additional training is needed to increase overall awareness among school staff and parents/guardians.

    AllergyAware, an online, asynchronous anaphylaxis training program, offers versions of its course in English and French, specifically for school personnel. Researchers used an evidence-based instructional design to develop, implement, and evaluate the AllergyAware e-learning course as a training resource for anaphylaxis education. The course incorporates best practices, using a combination of text, images, and videos to deliver educational content.

    For the pilot test, researchers enrolled 105 volunteers, including 74 individuals, which included elementary and secondary school teachers, administrators, educational assistants, librarians, and custodial staff. Participants showed improved anaphylaxis knowledge, with pretest scores averaging a mean (SD) 51.1% (15.8%) and posttest scores rising to 78.2% (16.2%).

    Technical challenges arose with three drag-and-drop sequencing questions on the pretest. These questions, which required users to scroll through multiple steps for autoinjector use, led to low pretest scores, with only 3%, 15%, and 18% correct responses. Despite these difficulties, posttest scores significantly improved to 49%, 70%, and 80% for the same questions. It’s important to note that these technical issues may have impacted the reliability of the assessment.

    Participants also improved their confidence in using an EAI, as measured by a 3 point Likert scale and their use of Twinject EAIs, both featured in the course’s initial version. Participants who reported very high confidence in using the EpiPen and Twinject doubled and tripled, respectively, from the pretest to the posttest.

    The study identified several key areas for improvement. Over half of participants (55%) disagreed that they could complete the program in a reasonable amount of time, with many noting in open feedback that the course took too long and the narration was too slow. Additionally, many participants felt frustrated with the “drag-and-drop” assessment items’ technical aspects when sequencing auto-injector steps. Lastly, stakeholders noted that most compliance training courses exclude pretests to reduce overall duration.

    Over the past 7 years, more than a quarter of users completed the course multiple times, and close to three-quarters (72.3%) completed the course a single time. Most participants who completed the English course were from Ontario (65.3%), followed by Alberta (16.7%) and British Columbia (12.5%). Participants from New Brunswick (41%), Québec (38%), and Ontario (15%) completed the French course. On average, sessions for participants without technical issues lasted 23 minutes and 38 seconds, which aligns with server estimates.

    After participants completed the AllergyAware course, they filled out a brief survey focused on their self-reported confidence with EAIs and emergency anaphylaxis management, their opinions on the course’s applicability and usefulness, and if they would recommend it to others. Over 95% of the 170,954 participants responded with “agree” or “strongly agree” to each self-confidence item. The comments were mostly positive, with a few respondents who felt that in-person training would deliver the course content more effectively than the online format.

    Participants also completed a 10 item knowledge quiz, achieving a mean score of 9.05 (0.18), with a modal score of 10. The pass rate per quiz attempt was 95.73% (1.16). Participants consistently answered scenario-based questions about recognizing anaphylaxis or administering epinephrine correctly.

    AllergyAware and other online education models limit the study’s results because they cannot train or assess EAI administration proficiency in person. Additionally, researchers could better assess longer-term knowledge transfer by employing a pretest, an immediate posttest, and a delayed posttest, rather than only using an immediate postcourse quiz. Another key limitation is that researchers do not directly assess anaphylaxis management in real-world settings; instead, outcomes rely on self-reported proficiency rather than observed practice.

    “Future research is needed to assess participants’ application of knowledge in real-world settings, including epinephrine autoinjector administration technique, long-term retention of key concepts, and impact on schools’ management of anaphylaxis,” study authors concluded.

    References

    1. Sharma B, Ayers S, Huang J, Gerdts J, Waserman S, Levinson AJ. Online food allergy and anaphylaxis education for school personnel is effective and scalable: experience with the AllergyAware e-learning portal from 2015 to 2022. Allergy Asthma Clin Immunol. 2025;21(30):1-10. doi:10.1186/s13223-025-00977-0
    2. CDC National School Food Allergy Guidelines. Food Allergy Research & Education. October 30, 2013. Accessed July 22, 2025. https://www.foodallergy.org/resources/cdc-national-school-food-allergy-guidelines
    3. National school policies. Food Allergy Canada. Accessed July 22, 2025. https://foodallergycanada.ca/professional-resources/educators/school-k-to-12/national-school-policies/

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  • Discussing Strategies to Manage Chronic Itch Among Patients, with Adam Friedman, MD

    Discussing Strategies to Manage Chronic Itch Among Patients, with Adam Friedman, MD

    One of the most difficult struggles many patients with dermatologic diseases face over the course of their condition is chronic pruritus, also known as itch. This topic was covered in a session at the Dermatology Education Foundation (DERM) 2025 NP/PA CME Conference.

    Addressing chronic pruritus and managing this symptom of disease was highlighted in a new HCPLive interview with Adam Friedman, MD, who serves as Professor, Chair of Dermatology, Residency Program Director, Director of Translational Research, and Director of the Supportive Oncodermatology Program in the George Washington University School of Medicine & Health’s Department of Dermatology.

    “I think one of the greatest struggles when it comes to managing a patient with pruritus, which, you have to understand, can be a symptom or a disease unto itself,” Friedman said. “Is it an itch that rashes, meaning you are manipulating the skin by scratching and now create visible change, or is a rash that itches a primary skin disease that is pruritic? That single question will veer you off into 2 very different directions. I would argue a rash that itches is probably a little easier to manage, because there are a plethora of possible things that can be driving the itch with no obvious primary cutaneous issue. With that in mind, you want an organized approach in order to figure out what could be driving disease.”

    Friedman spoke about some of the initial focus of labwork, including checking on issues with the liver, kidneys, and thyroid. He went on to discuss pruritus as a potential presenting sign of different forms of malignancy.

    “A chest X-ray I would certainly recommend in the right setting,” Friedman explained. “That is definitely one of the key takeaways: do not forget, pruritus can be a presenting sign of many different flavors of malignancy. Probably the best known would be lymphoma, and that’s where the chest X-ray comes in. Other key things not to miss know that bullous pemphigoid can just present as pruritus. Anywhere from 10 to 15% of patients can have no skin findings. Also, you never want to be humbled by scabies.”

    Friedman later went on to describe tips regarding treatment options for patients suffering from chronic itch.

    “We do have OTC and prescription options that are available to us,” Friedman said. “Probably the hottest thing out there is going to be your topical JAK inhibitors and PDE4 inhibitors, both of which have a unique influence on sensory neurons. Systemically, the take-home is that you should take a little from Aisle A, take a little from Aisle B, meaning go after neuropathic or nerve targeting therapies like SSRIs, gabapentinoids, in combination with anti-inflammatories. If it is a mixed picture, fortunately, we have some really amazing systemic agents that are meant to address inflammation but also will hit itch. I mentioned JAK inhibitors before, but we have a litany of biologics that target key cytokines or receptors that drive both inflammation and sensitization of those neurons. So be creative. Ask lots of questions.”

    For any additional information on the topics covered by Friedman in his session, view the full video segment posted above this summary. For more, view our latest conference coverage.

    The quotes used in this interview description were edited for clarity.

    Friedman has previously reported serving as a consultant to Dermira, Eli Lilly and Company, Encore Dermatology Inc, Exeltis, Galderma, IntraDerm, Johnson and Johnson, Oculus Innovative Sciences, Pfizer Inc, and Sanovaworks.

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  • Hedge Funds Trim Bullish Oil Position as Tariff Deadline Nears

    Hedge Funds Trim Bullish Oil Position as Tariff Deadline Nears

    Hedge funds cut their bullish position on US crude to the lowest since early April as President Donald Trump’s Aug. 1 deadline for trade deals stoked concerns the trade war will sap energy demand.

    Money managers decreased their net long position on West Texas Intermediate by 10,018 lots to 86,088 lots in the week ending July 22, weekly Commodity Futures Trading Commission data on futures and options show. That’s the lowest since April 8.

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  • Rogue black hole found terrorizing unfortunate star in distant galaxy

    Rogue black hole found terrorizing unfortunate star in distant galaxy

    A rogue, middle-mass black hole has been spotted disrupting an orbiting star in the halo of a distant galaxy, and it’s all thanks to the observing powers of the Hubble Space Telescope and Chandra X-ray Observatory. However, exactly what the black hole is doing to the star remains in question as there are conflicting X-ray measurements.

    Black holes come in different size classes. At the smaller end of the scale are the stellar-mass black holes born in the ashes of supernova explosions. At the top end of the scale are the supermassive black holes, which can grow to have many millions or billions of times the mass of our sun, lurking in the hearts of galaxies. In between those categories are intermediate-mass black holes (IMBH), which have mass ranging from hundreds up to 100,000 solar masses, or thereabouts.

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  • Echelon kills smart home gym equipment offline capabilities with update

    Echelon kills smart home gym equipment offline capabilities with update

    Some might never have purchased Echelon equipment if they knew the machines might one day fail to work without a web connection or Echelon account.

    Third-party app connections severed

    For some owners of Echelon equipment, QZ, which is currently rated as the No. 9 sports app on Apple’s App Store, has been central to their workouts. QZ connects the equipment to platforms like Zwift, which shows people virtual, scenic worlds while they’re exercising. It has also enabled new features for some machines, like automatic resistance adjustments. Because of this, Viola argued in his blog that QZ has “helped companies grow.”

    “A large reason I got the [E]chelon was because of your app and I have put thousands of miles on the bike since 2021,” a Reddit user told the developer on the social media platform on Wednesday.

    However, Echelon’s firmware update likely seeks to regain some of the revenue opportunities that overlap with the capabilities that apps like QZ enable. Echelon’s subscription-based app, which starts at $40 per month, also offers “guided scenic rides,” for example. QZ can allow people to watch Peloton classes from their Echelon device, but Echelon sells its own fitness classes. The Tennessee-headquartered company has been investing in ways to get customers more engaged with its personalized workout platform, too, which requires the machines to be online.

    There’s also value in customer data. Getting more customers to exercise with its app means Echelon may gather more data for things like feature development and marketing.

    Echelon is a private company, and we don’t know how much money it is making, but it’s likely that its financial goals hinge on subscription sales, which can generate more revenue than expensive equipment purchases. Meanwhile, Echelon is competing with other tech-centric companies offering gym equipment and classes, like the Peloton.

    Viola runs QZ, which costs $7 to $8 to download, alone, offering users a lot of support via online communities. He told Ars that revenue from app purchases covers his costs “more or less.”

    “It was never my intention to damage anyone’s business. This is just competition. The best product should prevail,” Viola said. “I never created QZ to get rich; I just wanted users to have a great hour of fitness when they choose, without connection issues, subscriptions, or [other limitations].”

    In terms of QZ, the user community is “working on a fully open-source Echelon controller to unlock bikes that have already received this update,” per Viola. It’s in the very early stages, he said.

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  • Stenshorne satisfied with top five in Spa Qualifying to continue Hitech TGR momentum

    Stenshorne satisfied with top five in Spa Qualifying to continue Hitech TGR momentum

    Martinius Stenshorne says he got the maximum out of himself and his Hitech TGR car in Spa-Francorchamps Qualifying to earn fifth place on the grid.

    The Norwegian driver says the session was a difficult one to handle with traffic and the preference of a slipstream made getting a clean run in far less straightforward than usual.

    Speaking afterwards in the paddock, Stenshorne says the team did a good job in managing things during what was a hectic session around the longest lap on the calendar.

    “It was typical Spa last push lap, everyone wants the draft. It was a good Qualifying overall. I think we were already competitive from Practice, we were P2, so it was good.

    “After the first lap as well in Qualifying, the cooldown lap after was quite chaotic but in the end, we managed to get a good position there as well, but the tyre just wasn’t there anymore.

    “It was a bit of a combination of both track position – which is important here. You can gain quite a bit of time in sector one and three, especially from the tow and not being too close to lose time when we get into sector two. But then you also need to do the job if you have a tow or not.”

    Reflecting further upon his result, the McLaren Development Driver says that he was able to extract the maximum from his session, but that the team would still have to keep on top of conditions come rain or shine tomorrow.

    “I’m quite happy with the result. I didn’t have too much more to be honest. But there are some things to fine tune. Tomorrow is the first race, so completely different scenario for the car perspective. But happy overall with P5 in this session.

    “Tomorrow looks okay but then Sunday I think there might be a bit more rain. So, we will have to see, it’ll be the same for everyone, you just have to be on the right tyres.

    Looking at his season overall, Stenshorne says that recent races have brought a step forward in terms of consistency after Hitech were able to find a detail that has improved their performance in the races.

    READ MORE: QUALIFYING: Benavides and AIX Racing earn first F3 pole in dramatic Spa session

    He will be hoping their pace from Spielberg in particular carries over into the races at Spa after a charge through the pack that ultimately led to his second race victory of 2025.

    “I’m happy because at the beginning of the season we were struggling with qualifying and race pace. In Barcelona we were quite poor in the races, to be honest, but from Red Bull Ring, we found some stuff which has worked quite well.

    “So we got a very good picture there and were good in the dry at Silverstone as well. I hope I can continue this momentum here as well.

    “It’s going to be interesting. It’s a long run to Turn 5, so it’s going to be about getting the right slipstream which is not always so easy. Anything can happen here, and starting from P7, let’s see what happens.”

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  • Clinical Trial Data on Incretin Therapies

    Clinical Trial Data on Incretin Therapies

    This transcript has been edited for clarity. 

    At the ADA meetings this year, incretin therapies were a big topic. There were many, many different studies presented on all sorts of new drugs and older drugs, and a large amount of interest in this. What I’m going to try to do is make it simple, and you’re going to have to forgive me because many of these drugs have names that are almost impossible to pronounce. 

    As far as I can tell, there were three main areas that involved incretins. One was newer agents that were different combinations of different kinds of drugs. I’m going to touch on those main areas where there were differences. The second is in terms of the forms for delivery, specifically a new oral form of incretin therapy that might be easier for patients to take. Third, longer duration of activity of these agents that might make it even easier for our patients to adhere to. 

    First, I’m going to go to different combinations. The first is CagriSema, which is semaglutide plus cagrilintide, which is a long-acting human amylin analog. We all were familiar with amylin from a long while ago, as we had pramlintide. This takes that amylin analog and mixes it with a dose of 2.4 mg of semaglutide. 

    The studies that they did are called REDEFINE, and they presented the full results of the phase 3 REDEFINE trials. In most of the studies on these newer agents, they basically study them in people who are overweight or obese without type 2 diabetes, as well as in people who are overweight or obese with type 2 diabetes. 

    REDEFINE 1 looked at 3417 people who were overweight or obese and who didn’t have type 2 diabetes. They saw 20% weight loss with this new agent compared to 15% with semaglutide 2.4 mg, or 12% weight loss with cagrilintide alone. 

    In REDEFINE 2, there were 1206 people with obesity and type 2 diabetes compared to placebo. CagriSema conferred a 13.7% weight loss vs 3.4% with placebo. 

    That’s fairly standard for many of these drugs. You get weight loss and A1c reduction, and it’s always a bit more in people without diabetes than those who have diabetes. 

    Moving on to the next combination. There was the DREAMS-1 trial, looking at a once-weekly GLP-1 receptor agonist combined with a glucagon receptor agonist, which is called mazdutide. It was studied in people in China with type 2 diabetes. This showed a nice A1c reduction and significant weight loss at 24 weeks. 

    This was a study in 319 individuals who were living in China. They had a number of different arms to this study, so they had a 4-mg dose, a 6-mg dose, and placebo. The study lasted for 24 weeks, and they saw A1c reductions of 1.4%-2%. There was weight loss that varied depending on the dose, at 5.6% or 7.8% in the two different arms. 

    There were similar side effects. I think one of the truths of all of these trials is that the GI side effects occur with nearly all of these agents, some to a greater degree than others, but those were the major side effects in terms of this agent. 

    They’re now studying it in other individuals with type 2 diabetes. They compared it to dulaglutide and found a greater A1c reduction than with dulaglutide in one trial. They’re also looking at it for weight loss in people without diabetes. There are a number of trials that are ongoing that will give us more data in terms of what this combination does in people with obesity and type 2 diabetes. 

    The next trial is one that I find oddly fascinating, which is called the BELIEVE trial. Believe it or not, this is a trial in which they took semaglutide and mixed it with a monoclonal antibody that blocks activin type II receptors, with the hopes that that will improve muscle mass, maintain lean body mass, and decrease fat mass as people lose weight with this combination. 

    They studied it in people who were living with obesity or overweight without type 2 diabetes, and they basically had a number of different comparisons. The monoclonal antibody is called bimagrumab. It’s something that I’m not familiar with, but it was really interesting in terms of its effect. 

    They had a number of different groups: a placebo group, a low-dose bimagrumab group, a high-dose bimagrumab group, a low-dose semaglutide group, and a high-dose semaglutide group, and then they had four different combination groups with low-dose or high-dose bimagrumab. They looked at all of these different permutations in a study sample size that was 507 individuals.

    They were hoping to see less loss of lean body mass, and they basically showed this. There was a 7.9% reduction in lean body mass with semaglutide alone, but if you gave them the monoclonal antibody, there was a 2.3% gain in lean body mass. When you combined the monoclonal antibody with semaglutide, you got a lesser reduction in lean body mass, a 2.6% reduction, which was compared to the 7.9% reduction with semaglutide alone.

    This is hopeful in the sense that this specific combination helps people lose less lean body mass. There were a whole bunch of other analyses they did to see about people being stronger and feeling better. It really does matter to not lose so much lean body mass. 

    I’m still old fashioned and I really want to encourage people to exercise and eat well in order to help preserve lean body mass. We’ll see what happens with this. I think it’s a fascinating concept, but I also don’t want to forget about lifestyle. 

    The next trial was called ACHIEVE-1, and this was looking at an oral form of a GLP-1 receptor agonist known as orforglipron. They studied this in people with type 2 diabetes.

    What’s different about this is that this is a small molecule. It’s not a peptide GLP-1, so it’s really easy to give. It’s like any old pill that people take, so it doesn’t have restrictions around how much water and when it’s taken, etc. 

    They did see benefit in terms of A1c reduction, some weight loss, about 8%, and it seemed like it worked, but it did have GI side effects and it didn’t cause the same sort of A1c reduction or weight loss we see with some of the other injectable compounds. Still, it might be an interesting first step for people as they get used to GLP-1 receptor agonist therapy, and it may be easier for patients to take. 

    The final compound I’m going to discuss is MariTide. This is a compound that is a GLP-1 receptor agonist and a GIP antagonist. This is a once-a-month agent. This was a 52-week trial in individuals who were obese or overweight without type 2 diabetes. They basically had three different doses they were studying and they did a bunch of different dosing frequencies. 

    It seemed to me to be effective in terms of weight loss, as most of these drugs are, but it did have an incredibly high rate of GI side effects. When you look at that study in individuals without type 2 diabetes, the rates of nausea and vomiting were really high. 

    At baseline, 25% of placebo patients reported nausea. In the treatment group, nausea was reported in 77%-87% of participants and vomiting was reported in 68%-92%. It usually occurred after the very first dose of the drug, with an incidence decreasing over time. I’ve never used a drug that had such a high rate of vomiting — nausea, potentially, but not vomiting. GI side effects were the main reason for people stopping it, and 14%-29% of individuals discontinued the drug due to adverse events. 

    They also did a study in people with type 2 diabetes. It’s interesting because they used a different survey to assess GI side effects, but they still had a very high rate of GI side effects, at 94% in the MariTide group vs 81% in the placebo group. Again, the most common GI side effects were nausea, vomiting, constipation, and diarrhea. Nausea rates ranged from 41% to 59% of people taking the MariTide, with vomiting in 45%-75% of participants. 

    These GI side effects are really clear here, and I don’t know that this is going to be something people are going to want to take. Once a month is nice, but it’s not fun to vomit. I think it depends on how quickly people habituate to this and how one goes up on the dose. 

    These GI side effects are an issue for all of us and our patients as we prescribe these drugs. I tend to start as low as I possibly can. I’m a fan of microdosing as much as possible to get people to tolerate these drugs because I think that the incretin class of drugs is so beneficial, not only in terms of glucose and weight loss, but also in its nonglycemic effects. 

    I also don’t want people to lose weight too fast because I think that it isn’t healthy. I know that there are studies that are coming out that show that there are people who respond by very rapid weight loss, more commonly in women than in men. I think we need to be mindful of how we use these drugs, how quickly people lose weight, and how we encourage people in terms of leading a healthier lifestyle to avoid some of the side effects that can be associated with that sort of rapid weight loss. 

    This has been Dr Anne Peters for Medscape.

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