Researchers headed by a team at the Institute of Metabolic Science, University of Cambridge, have solved the mystery of why both stimulating and blocking a particular receptor, or switch, in the brain can help people lose weight. Their study in mice indicated that the answer lies in where the receptor, called GIPR, is located. The results showed that stimulating this switch in the brainstem suppresses appetite, while the same effect can be achieved by blocking it in the hypothalamus. The researchers say their findings could help in the development of more effectiveness therapeutic strategies.
Jo Lewis, PhD, at the Institute of Metabolic Science at the University of Cambridge, said, “Understanding which brain circuits respond to these medications—and how they do so—could help us design better drugs that produce more weight loss with fewer side effects, and which might work in combination with other obesity medicines to even greater effect.” Lewis is first author of the team’s published paper in Nature Metabolism, titled “Distinct brain regions mediate regulation of food intake in response to GIPR agonism or antagonism.”
More than a billion people worldwide are living with obesity, which increases the risk of diseases such as type 2 diabetes (T2D), cardiovascular disease (CVD) and cancer. Weight loss can help mitigate these complications, but losing weight through diet and exercise alone can prove challenging.
In the past few years, a new generation of weight loss drugs has emerged that target particular receptors in the brain, reducing appetite and leading to weight loss, as well as helping to control blood sugar levels. Several of these drugs, such as Wegovy and Ozempic, work by stimulating the glucagon-like peptide 1 receptor (GLP-1R).
Other weight loss drugs act on both this receptor and on GIPR. “The development of dual agonists for the glucagon-like peptide-1 receptor (GLP-1R) and glucose-dependent insulinotropic polypeptide receptor (GIPR) has been a landmark moment in the treatment of type 2 diabetes and obesity,” the authors wrote.
However, some drugs, such as Mounjaro and Zepbound, stimulate GIPR, while others, such as the Phase III-stage MariTide, block it. Why these opposite actions have the same result has puzzled scientists. “… for reasons that are incompletely understood, in preclinical and clinical studies, adding either a GIPR agonist or GIPR antagonist to GLP-1R agonism causes additional weight loss,” the team continued. “There is emerging evidence that GIPR agonism and antagonism exert their paradoxically similar effects on weight loss via distinct neuronal populations.”
The investigators’ newly reported preclinical research has now shown that the two different types of GIPR drugs act on distinct regions of the brain, but also that they can boost weight loss when combined with certain GLP-1-based weight-loss drugs. For their reported study the team turned to genetically engineered mice and selectively removed GIPR from different parts of the brain to see which regions were responsible for the effects of the obesity drugs.
One group of mice lacked GIPR in the brainstem—the area at the base of the brain, just above the spinal cord, involved in appetite and nausea. A second group lacked GIPR in the hypothalamus, a major center controlling hunger and body weight. A third, control group included normal, unmodified mice. The researchers treated the mice with various combinations of a GIPR agonist (which activates the receptor), a GIPR antagonist (which blocks the receptor) and a GLP-1 drug, and measured food intake, body weight, fat mass, glucose control and brain activity.
“We knock out Gipr in either the area postrema (AP) or hypothalamus of mice (GiprAP-KO and Giprhypo-KO, respectively) and compare body weight and food intake responses to GIPR agonists and antagonists, alone and in combination with the GLP-1R agonist liraglutide,” they wrote in summary.
By comparing the responses of normal mice with mice lacking GIPR in different brain areas the investigators showed that GIPR agonists act on the brainstem to suppress appetite and reduce weight. They then showed that GIPR antagonists help weight loss by acting on this receptor in the hypothalamus, where they release a “brake” that otherwise limits the brainstem’s ability to respond to signals telling us we are full. Blocking GIPR also appeared to boost the effect of emerging new drugs targeting the amylin receptor—such as cagrilintide (Cagri)—suggesting that GIPR antagonists could potentially be used to strengthen several types of anti-obesity medicines.
“Overall, our results suggest that the AP is responsible for the appetite-suppressing effects of GIPR agonism but that GIP receptors in the hypothalamus underlie the ability of GIPR antagonism to enhance the weight loss effects of GLP-1R and amylin receptor agonists,” they stated. “GIPR antagonism and Giprhypo-KO also sensitize to cagrilintide-induced weight loss.
The findings explain why drugs such as MariTide, which combines GIPR antagonism with GLP-1 receptor agonism, are effective, and suggests how to design even better combination therapies. And as the authors noted, “Future work is still, however, required to identify the neuronal networks underlying GIPR interactions in the AP and hypothalamus and their crosstalk with other appetite-regulating circuitry.”
Lewis said the work strengthens the idea that the brain is central to obesity treatment, commenting, “Obesity drugs are not acting simply on the gut or pancreas. Instead, they have important effects on specific, identifiable brain circuits that regulate appetite and food intake.”
Axiom Biosciences, a privately held developer of regenerative therapies and targeted biologics that rebranded last month from Cytonus Therapeutics, made headlines around the world when it announced plans to go public through an initial public offering (IPO), since companies that go public typically do so quietly, by filing registration statements with regulators and exchanges.
What made Axiom’s IPO plans even more newsworthy: the San Diego-area company (based in suburban Carlsbad, CA) said it intends to trade its first public shares on the Hong Kong Exchange (HKEX) rather than a U.S. market like Nasdaq, the leading market for biotech IPOs, or the New York Stock Exchange.
Why Hong Kong? Axiom says the special administrative region of China possesses deep biotechnology expertise, a strong appetite for clinical-stage innovation, and direct proximity to the Asian partners and capital advancing the company’s science.
“For us, Hong Kong is a very good fit for the stage of company that we’re in, and the timing is right,” Remo Moomiaie-Qajar, MD, Axiom’s founder, CEO, and chairman, told GEN. “Hong Kong has a very well-established investor base that really understands the time requirements and the capital needs for biopharma, but in particular, cell therapies. And ultimately, given the fact that we have been working in Asia with partnerships for several years, this landing spot for us in Hong Kong seemed to be the right choice in a broader strategy.”
Does that mean the United States is finished for biotech innovation?
“I would not state that at all,” he replied. “I think the United States is very much still a leader. It is also very central to our strategy, and the FDA is really core to all of our decisions moving forward into clinics. I just see that this is, and I speak only for us, part of a bigger global strategy which includes both Asia and the United States.”
“Ecosystem to thrive”
Remo Moomiaie-Qajar, MD, Axiom Biosciences founder, CEO, and chairman
However, Axiom has publicly offered other reasons for its move that convey a warmer biopharma climate in Hong Kong compared with the United States. In its announcement, the company said its Hong Kong IPO plans were “reflecting a broader shift in where the world’s most ambitious science finds the ecosystem to thrive.”
And speaking on CNBC, Moomiaie-Qajar raised a concern with the U.S. biopharma climate when it comes to financing: “Some of the most important science in the world is being built in the United States, but the way it gets funded hasn’t kept pace.”
He elaborated on that remark, telling GEN: “That speaks to a broad range of problems that we have in financing within this industry. In particular, I was referencing the private side.”
“The reality is, as you progress with your pipelines and you cross over the threshold of being a clinical stage company, and then you have clinical success, it requires a significant amount—more capital to get your assets to move forward, and hopefully, to a BLA [Biologics License Application],” Moomiaie-Qajar explained. “But the number of check writers diminishes at the same time. So, there is seemingly no shortage of capital within biopharma, but I do believe there’s a financing issue and an access issue.”
Hence Axiom’s exploration of whether this was the right time to go public—a question Axiom is answering in the affirmative: “Hong Kong, given our strategic fit, and relationships and proximity to our partners in Asia, was the right first decision in establishing our public identity as a company.”
Comeback mode
The IPO market has been in comeback mode most of this year, with 14 companies selling their first public shares on U.S. markets since January, and another five doing so overseas, in Asian markets that include the Tokyo Stock Exchange, South Korea’s tech-focused KOSDAQ, and the Hong Kong Exchange.
The biggest American biotech IPO—this year, and of all time—was an upsized offering that took place last month, when Parabilis Medicines (Nasdaq: PBLS) raised an eye-popping $770.5 million in gross proceeds by selling some 38.5 million shares at $20 per share. Parabilis’ shares have risen 56% since then, to $31.28 at Friday’s closing bell.
The latest biotech IPO, also upsized, came on Thursday when Scribe Therapeutics (Nasdaq: SCTX), a developer of in vivo CRISPR gene-edited therapies, raised $128.7 million gross by selling 8.58 million shares at the high end of its price range at $15 per share. The shares jumped 44% on Friday, finishing the day at $21.65. Scribe also raised another $7.5 million gross by selling 500,000 shares at the IPO price to Sanofi (Euronext Paris: SAN) in a concurrent private placement.
But the best-performing U.S. biotech IPO is Veradermics (NYSE: MANE), a developer of treatments for dermatology and aesthetic conditions whose shares have catapulted more than six-fold, rocketing 545% since pricing its IPO at $17 per share on February 3, closing Friday at $109.66 per share. Earlier this month, Veradermics announced positive topline results from its open-label Phase II Study 207 trial (NCT06527365) assessing VDPHL01, an extended-release oral minoxidil formulation, in women with mild-to-moderate pattern hair loss.
Hong Kong’s largest biotech IPO so far this year is Suzhou Ribo Life Science (6938.HK), a developer of oligonucleotide treatments based on RNA interference and other technologies. Ribo raised more than HKD 1.8 billion ($229.5 million) by selling 31,610,400 shares at HKD 57.97 ($7.39) on January 9. Since then, however, Ribo’s stock price has dipped 7.5%, closing Thursday at HKD 53.60 ($6.83).
Also going public via HKEX this year were medtech companies such as Hangzhou Diagens Biotechnology(2526.HK), a developer of artificial intelligence (AI)-based medical imaging tools whose customers include specialized genomics research labs and cytogenetics labs, as well as hospital pathology departments. Diagens went public March 30, raising about $101 million by selling 7,999,200 shares at HKD 99.00 ($12.62)—a price that has since more than doubled, leaping 172% after closing Friday at HKD 269.00 ($34.30).
HKEX lists 84 biotech companies, compared with more than 600 for Nasdaq, according to their respective websites.
Staying in America
Over time, Axiom plans to pursue a secondary stock listing in the United States. Moomiaie-Qajar says Axiom will remain an American company: “We are a U.S.-based, U.S.-headquartered company that is going to be something that does not change.”
Axiom says it intends to be the first U.S. biotech company planning to go public in Hong Kong. That’s the path that was successfully trod by AI-based drug developer Insilico Medicine (3696.HK) when it went public in December, raising HKD 2.277 billion (about $292.3 million at the time; now worth $290.3 million) on the Hong Kong Exchange by selling 94,690,500 shares at HKD 24.05 ($3.08, now worth $3.06) each.
Insilico’s stock has nearly doubled, soaring 96% since then, closing Friday at HKD 47.06 ($6.00) thanks to several collaborations with biopharma giants and an upbeat revenue and profit forecast for the first half of 2026.
“From my perspective, it certainly seeded a little bit of certainty in my mind that this was a good decision, because they’ve done really well post-IPO,” Moomiaie-Qajar commented.
Insilico’s parent InSilico Medicine Cayman TopCo lists a registered office in the Cayman Islands, while Insilico’s website lists additional offices in Cambridge, MA (announced in 2024 as the company’s headquarters), New York, Montreal, Abu Dhabi, Hong Kong, Shanghai, and Taipei.
“Very high listing standards”
“One of the reasons you would list in Hong Kong is to openly compete with the companies in the ‘China Gym’ and also take advantage of the increased visibility and transparency with the very high listing standards,” Alex Zhavoronkov, PhD, Insilico’s chairman, executive director, CEO, and CBO, told GEN.
“Many companies want to list there. But the barriers for listing are very high even for the biotech track.”
A company planning to go public, he explained, needs not only an asset in Phase II studies, but a clear funding history from credible investors, several years’ worth of cash to operate, and a level of corporate stability that the exchange will assess.
“For very early biotech companies it may be much easier to list in the United States,” Zhavoronkov said. “In general, it is a positive trend because biotech must become more international and collaborate and compete internationally. Competing for capital is the advanced form of competition because finance usually runs biotech—you cannot discover and develop drugs without it. Companies and ideas in biotech should become more fluid internationally. Public listings make companies and ideas more competitive and transparent.”
Together with Seoul-based, privately held Medinno, Axiom has co-developed its lead regenerative therapy based on umbilical cord-derived, conditioned mesenchymal stem cells (MSCs) sourced from Wharton’s Jelly. The therapy is under study in two pipeline programs that aim to treat newborns with severe brain injury: AX-007 for intraventricular hemorrhage (IVH); and AX-008 for hypoxic-ischemic encephalopathy (HIE).
Positive Phase I results
Earlier this month, Axiom announced positive results from a Phase I dose-escalation study assessing the safety, tolerability, and preliminary efficacy of the regenerative therapy across a range of doses in nine newborns—five diagnosed with severe IVH, four with HIE—following direct administration into the central nervous system.
Across all doses studied, the MSC therapy achieved a 0% mortality rate at 12 months compared to the historical natural 46% mortality rate within the first year of life for infants with severe IVH. The therapy also showed a favorable safety profile, with no treatment-related serious adverse events seen.
“We’re now in discussions with the FDA to move those programs into the next stages, which would be a Phase IIb study,” Moomiaie-Qajar said. The FDA has granted AX-007 and AX-008 its Rare Pediatric Disease and Orphan Disease designations.
Axiom is also evaluating an expansion of its therapy development into adult ischemic stroke, which affects approximately 700,000 adults annually in the United States, and additional neurological indications.
“We feel very confident that given our clinical trial success in Phase I, the expansion of our valuable asset into three, four indications is going to be a good basis for us to launch our IPO, but then after the IPO really go further and deeper into our pipeline that we’ve been developing for eight years,” Moomiaie-Qajar said. “We have a lot now that we need to translate into clinics.”
Leaders and laggards
Immix Biopharma (Nasdaq: IMMX) shares tumbled 14% from $10.25 to $8.80 on July 20 following the arrest of Ronald L. Fischer, 70, who was one of Rhode Island’s Most Wanted fugitives—and who, under the alias of Richard Graydon, MD, PhD, served as the company’s CMO. Fischer was arrested by federal and Rhode Island authorities off the coast of New Jersey on a U.S. Marshals Service Unlawful Flight to Avoid Prosecution warrant, having been a fugitive since fleeing Rhode Island during a criminal trial in 2005, the U.S. Justice Department stated. Fischer was convicted in absentia of First-Degree Sexual Assault after failing to appear for trial and remained wanted for Failure to Appear, First Degree Sexual Assault, and Flight to Avoid Prosecution. Authorities also said Fischer was living on a 56-foot sailing vessel called The Silver Lining, which was registered under the Graydon name. As “Graydon,” Fischer was appointed Immix’s CMO in March, the company announced March 30 in a press release no longer posted on its website. “As of July 17, 2026, Richard Graydon has been terminated and is no longer with the company for reasons unrelated to his activities at the company,” Immix disclosed in a July 20 regulatory filing, adding: “Given his short tenure, management believes there is no material effect on the business.”
Novocure (NVCR) shares jumped 28% from $15.57 to $19.99 Thursday after the Swiss-based oncology drug/device developer developer of the Tumor Treating Fields (TTFields) cancer therapy reported second quarter adjusted earnings before interest, taxes, depreciation, and amortization (EBITDA) of $10.757 million, vs. an adjusted loss of $9.934 million a year earlier, on net revenue that rose nearly 16% year-over-year, to $183.584 million from $158.805 million. Novocure still finished Q2 in the red with a net loss of $15.658 million, improved from the $40.139 million net loss of the second quarter of 2025. Novocure credited its 18% global active patient growth across indications for the positive numbers; as of June 30, more than 280 active patients were on Optune Pax®, a wearable device designed to deliver its TTFields therapy for adults with locally advanced pancreatic cancer concomitant with gemcitabine and nab-paclitaxel. “The main takeaway is that the early U.S. adoption of Optune Pax is off to an encouraging start,” J.P. Morgan analyst Jessica Fye wrote in a research note. Novocure shares reached a 52-week high of $21.35 at the start of the trading day before sliding 12% to $17.65 on apparent profit-taking.
Researchers from University College London in England have created the most comprehensive molecular map to date of severe preeclampsia, uncovering distinct fetal and maternal drivers of the disease that could lead to more targeted therapies and earlier intervention.
The study, published in Science Advances, combined single-cell RNA sequencing with spatial transcriptomics across the entire fetal-maternal interface and found that severe preeclampsia is not solely a placental disorder. Instead, the disease involves coordinated dysfunction across multiple maternal and fetal tissues, with different molecular programs emerging in early- versus late-onset disease.
Preeclampsia affects 2% to 4% of pregnancies worldwide and remains a leading cause of maternal and fetal illness and death. Although it is traditionally viewed as a placental disease, the mechanisms responsible for widespread maternal inflammation and endothelial dysfunction have remained unclear.
To better define those mechanisms, investigators analyzed tissues from 20 pregnancies, including 10 women with severe preeclampsia and 10 gestational age-matched controls between 25 and 37 weeks of gestation. By matching pregnancies by gestational age rather than comparing preterm cases with healthy term pregnancies, the researchers were able to distinguish disease-related molecular changes from normal developmental differences.
The analysis revealed extensive placental abnormalities, including molecular signatures of hypoxia, angiogenic imbalance, fibrosis, and altered metabolism. The team also confirmed impaired invasion of fetal extravillous trophoblasts into the maternal uterus, a hallmark of preeclampsia that contributes to defective remodeling of maternal blood vessels.
Beyond the placenta, however, the study identified previously unrecognized maternal immune abnormalities extending into the myometrium and chorioamniotic membranes. These included widespread mitochondrial dysfunction, activation of type I interferon signaling, and altered macrophage responses, providing a potential explanation for the systemic inflammation and endothelial injury that characterize severe disease.
The findings point to several potential therapeutic targets. Leptin (LEP), which was strongly upregulated in placental cells throughout both early and late disease, may contribute to oxidative stress and vascular dysfunction. The researchers suggest that leptin antagonists, already under investigation for autoimmune diseases, warrant exploration as placental-targeted therapies.
The study also highlights type I interferon signaling as a promising target. Elevated interferon activity, detected in maternal immune cells and peripheral blood, could potentially serve as both a biomarker and a therapeutic target for anti-interferon or antioxidant treatments.
“IFN-I in peripheral blood promises better screening of patients that might benefit from anti-IFN or antioxidant therapeutics,” the authors concluded.
Perhaps most importantly, the molecular abnormalities were substantially more pronounced in early-onset disease, suggesting that intervention before clinical deterioration may offer the greatest benefit.
“Given the severity of molecular dysfunctions in early disease, compared to its late presentation, timely intervention during gestation is likely beneficial and could change the extremely poor prognosis of severe PE,” the authors wrote.
Conditions: Anorexia in Adolescence; Anorexia Nervosa; Anorexia Nervosa, Atypical; Anorexia Nervosa, Binge Eating/Purging Type; Anorexia Nervosa Restricting Type; Anorexia Nervosa With Significantly Low Body Weight; Body Composition Changes; Growth & Development; Malnutrition Severe; Malnutrition, Calorie
Sponsors: University of California, San Francisco; Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); Denver Health and Hospital Authority; University of Hawaii
Those living with type 1 diabetes not only face the challenges of living with a chronic illness, but they also contend with the potential of developing secondary conditions, including kidney disease. Nearly a third of patients with type 1 diabetes develop kidney disease, resulting in diabetes as the leading cause of kidney disease worldwide. With such a broad impact, and few approved therapies, research into therapeutic strategies to help patients prevent or recover from diabetes-induced chronic kidney disease is much needed.
Research on type 2 diabetes suggests that inhibitors against the SGLT2 protein improve function and reduce damage to kidneys. Thought the mechanism behind this protective effect remains unclear, an SGLT2 inhibitor, dapagliflozin, has shown success in clinical trials led by Petter Bjornstad, MD, physician-scientist and executive director of the University of Washington Medicine Diabetes Institute.
Bjornstad & colleagues have developed their clinical trial to assess the effects of dapagliflozin in adolescents. Their new paper published in Science Translational Medicine shows the results of a section of their phase III data from the Adolescent Type 1 Diabetes Treatment With SGLT2i for hyperglycEMia & hyPerfilTration (ATTEMPT) trial.
The authors described this analysis of the broader trial as “a multimodal view of how the kidney of a person with T1D responds to SGLT2 inhibition.”
Data from 98 children aged 12 to 21, was analyzed to detail the effects of dapagliflozin in combination with insulin therapy on kidney function and physiology. Participants in both a placebo-control group and the treatment group were treated for 16 weeks, then underwent “sequential kidney biopsies, multiparametric kidney MRI, and plasma/urine proteomics,” though biopsies were only carried out in patients over 18 years of age.
Molecular profiles of the serialized biopsies showed a reversal of molecular hallmarks including transcriptional shifts using single-cell RNA seq, downregulation of glycolysis, gluconeogenesis, and oxidative stress markers, and reduced inflammatory gene expression.
“These molecular changes paralleled clinical improvements, including attenuation of hyperfiltration, improved glycemic control, and normalization of medullary oxygenation,” the authors wrote.
Analysis of proteomics in urine samples showed similar results. The tissue changes included decreased injury markers and increased numbers of protective proteins, suggesting that dapagliflozin has a reversing effect on diabetes-induced kidney damage.
“Cross-cohort comparison against healthy controls showed that over 55% of dapagliflozin-responsive genes shifted toward healthy control expression patterns,” indicated the authors.
Not only were kidney markers improved in treated patients, but these patients also showed overall improvement including improved blood sugar control and more normal kidney function.
“Because adjunctive SGLT2 inhibition is considered for people with T1D in the future, our results offer mechanistic reassurance that the drug engages kidney-protective pathways similar to those in type 2 diabetes,” they wrote.
In addition to determining the mechanistic impacts of dapagliflozin in kidney disease using a subset of data from a clinical trial, the authors point out that this work has a broader impact for other clinical trials with multiple data streams.
“Our study showcases the power of deep phenotyping in clinical trials to elucidate drug mechanisms in vivo,” they point out.
“Ultimately, combining rigorous clinical trials with translational science approaches will accelerate the development of therapies to reduce the burden of DKD in T1D,” concluded the authors.
People with diabetes who use a popular long-acting insulin pen made by Sanofi have had to become pharmacy scouts in recent weeks as they encounter supply issues.
The Lantus Solostar pen containing 3 milliliters of insulin glargine has been running low for several weeks because of increased demand “driven by broader market dynamics,” a Sanofi spokesperson told STAT. The issue is not technically considered a shortage by the Food and Drug Administration, but patients are nonetheless having trouble finding the medication.
“Our priority is ensuring patients have access to their medications,” the spokesperson said. “This is a temporary situation that we anticipate will improve over the coming weeks.”
Samsung Biologics made an all-cash public tender offer of approximately $1.8 billion to acquire Switzerland-based PolyPeptide Group, a CDMO specializing in peptide-based active pharmaceutical ingredients (APIs).
Samsung views the deal as expanding its capabilities beyond antibodies and ADCs to include peptide therapeutics, particularly in obesity and diabetes, including GLP-1 therapies, while advancing innovation across high-growth areas such as oncology and other emerging indications. The transaction brings together Samsung Biologics’ global manufacturing scale with PolyPeptide’s specialized peptide expertise to create a differentiated, end-to-end multi-modality CDMO platform, notes a Samsung spokesperson.
PolyPeptide operates an integrated development-to-commercial model with growth focused on a modular, automation approach which, the company points out, gives it the flexibility to adapt quickly to changing market demand.
The planned acquisition extends beyond adding capacity in that it also lays the foundation for Samsung Biologics’ next phase of growth, supported by a strong pipeline of active peptide projects that includes a deep late-stage portfolio, notes a Samsung official. PolyPeptide operates global sites across Sweden, Belgium, France, the U.S., India, together with a corporate office in Switzerland and a separate Innovation Center in Strasbourg, France, with capabilities in R&D, development, and commercial manufacturing.
Upon completion of the transaction, Samsung will bring together PolyPeptide’s experienced team and specialized peptide expertise with Samsung’s scientific and manufacturing strengths and global operations, says John Rim, chairman of the board of directors and CEO of Samsung Biologics.
“This acquisition reinforces our long-term growth strategy by not only broadening our service portfolio with modality expansion into peptides including GLP-1, but by also boosting our geographic reach and proximity further within the U.S., Europe, and India,” continues Rim.
“After a comprehensive review of strategic options, the Board is convinced that Samsung Biologics’ offer is compelling for our shareholders, delivering an attractive cash price and immediate, certain value today,” adds Peter Wilden, chairman of the board of directors of PolyPeptide. “At the same time, it represents a transformational opportunity to accelerate our strategic ambitions at a scale we could not reach alone.”
Eli Lilly reported more results Thursday showing that its next-generation obesity drug is highly efficacious at weight loss, but the data from the study, focused on people with heart disease, aren’t enough to answer a critical question about the therapy — whether it reduces cardiovascular risk.
The Phase 3 study enrolled nearly 2,000 people with severe obesity and heart disease, with or without diabetes. Those on the highest dose of the drug, called retatrutide, lost 22.6% of their weight after 80 weeks, while those on placebo lost 3.2%, when analyzing only the participants who stayed on treatment.
However, on additional analyses that looked at the occurrence of major cardiovascular events such as death, heart attack, or stroke, those taking retatrutide did not have a statistically significant lower risk of major events than those on placebo. Lilly said the trial was not powered to study cardiovascular outcomes and there were fewer heart events than anticipated.
Scientists in Switzerland have developed a portable breath detector that can accurately measure acetone released into the breath when the body burns fat. The smartphone-assisted device allows patients to monitor their metabolism at home and could help doctors personalize treatment for metabolic diseases such as obesity and diabetes.
Acetone levels in the breath have long been recognized as an indicator of metabolic activity, since its concentration rises when the body shifts from using carbohydrates to fats as the primary energy source. However, accurate measurements have traditionally required bulky and expensive laboratory equipment, while consumer devices have lacked the sensitivity needed to reliably measure acetone, especially at lower concentrations.
“If we want to make that information available to patients, we need to shrink those technologies into compact, user-friendly devices,” said Andreas Güntner, PhD, assistant professor at ETH Zurich and senior author of the study published today in the Device journal.
To make a compact breath analyzer, Güntner’s team used a chemoresistive sensor that changes its electrical properties in the presence of acetone. These types of sensors are known for their high sensitivity, rapid response, low power consumption, and small size. During each measurement, the accompanying smartphone app coaches users to exhale with the right force and duration, while quality controls can reject improper breaths or contaminated air. This design makes the sensor easy to use while ensuring accurate measurements.
The breath detector was used to analyze 312 breath samples from 12 healthy adults, with measurements closely matching those obtained using gold-standard mass spectrometry. “These findings show that we have the high performance needed for applications such as clinical studies, where you really want to distinguish these slight differences in fat metabolism,” said Simone Hersberger, graduate student at ETH Zurich and first author of the study.
The researchers then used the sensor to monitor breath acetone under four metabolic scenarios: light exercise followed by a high-carbohydrate meal, intense exercise followed by a high-carbohydrate meal, a high-fat ketogenic meal, and fasting. Breath acetone levels remained low during light exercise but increased with intense exercise, dropping after a high-carbohydrate meal. Acetone levels rose after a ketogenic meal and increased further during fasting.
Through Alivion, a spin-off from ETH Zurich, the technology is already available to individuals interested in tracking breath acetone to monitor weight loss and athletic performance. The device is currently being used to monitor individual progress in clinical studies of epilepsy, where a ketogenic diet is a standard medical treatment.
“Now it’s really time to spread it out into clinical trials and answer questions such as the effectiveness of different fasting therapies by providing personalized guidance,” said Güntner. “We’re really moving toward healthcare solutions that, in the future, you won’t need to go to the hospital for anymore. You’ll be able to do them at home.”
