Five-minute test conducted during routine health appointments could prevent stroke: Study

People at risk should be tested for atrial fibrillation every time they attend a health appointment, according to results of the AFFECT-EU project, which is holding its final event today in Brussels, Belgium. Patients at high risk of the disorder, such as those with heart failure or prior stroke, should be invited for a screening test.

Scientific coordinator Professor Renate Schnabel of the University Hospital Hamburg-Eppendorf, Germany said: “Screening for atrial fibrillation can identify undiagnosed atrial fibrillation so that the condition can be managed according to guidelines, including starting anticoagulation medication to prevent strokes. AFFECT-EU has concluded that opportunistic screening, where at-risk groups are screened when they contact the healthcare system, plus targeting patients at particular risk, may be a productive and cost-effective way to implement screening across Europe.”

Atrial fibrillation is the most common heart rhythm disorder globally. The number of adults aged 55 years and older living with the condition in the European Union is expected to more than double from 8.8 million in 2010 to 17.9 million by 2060.2 People with atrial fibrillation are up to five times more likely to have a stroke than their healthy peers. The disorder often has no symptoms and remains undiagnosed until a stroke occurs.

The four-year, EU-funded AFFECT-EU project brought together healthcare professionals, patient representatives, payers, and industry in a consortium of 26 partners, including the European Society of Cardiology (ESC), to define a feasible atrial fibrillation screening strategy for healthcare systems across Europe, with the ultimate aim of preventing subsequent strokes and premature death.

The ability of atrial fibrillation screening to reduce strokes was identified by the consortium in a contemporary meta-analysis in 35,836 participants. A further study by the consortium in 11 European countries found that there were no national screening programmes, and most atrial fibrillation was detected in patients with symptoms. But in a survey conducted by the group in 18 European countries, GPs said screening for atrial fibrillation was nearly as important as screening for common cancers.

A subsequent analysis by project members demonstrated that screening result in savings of stroke-related costs regardless of the method (e.g. opportunistic or targeted). Project members then developed a budget impact analysis calculator that can be used by health regulators and payers to estimate the financial impact of implementing a screening programme over a five-year period.

Regarding who is at elevated risk of atrial fibrillation or stroke and should therefore be screened, studies by consortium members identified that the following are risk factors: increasing age, obesity, high blood pressure, and high blood levels of N-terminal pro B-type natriuretic peptide (NT-proBNP), which is commonly tested to diagnose heart failure.

Project manager Daniel Engler of the University Hospital Hamburg-Eppendorf, Germany said: “People with atrial fibrillation are more likely to be severely disabled or die from a stroke or heart failure than those without atrial fibrillation, making prevention an imperative to reduce morbidity and maintain a high quality of life. AFFECT-EU has paved the way for well-implemented atrial fibrillation screening programmes to increase the number of new diagnoses, leading to guideline-adherent care, thereby reducing stroke risk and atrial fibrillation disease burden.”

Powered by WPeMatico

FDA Approves First Gene Therapy for rare genetic disease affecting brain and nervous system in kids

The U.S. Food and Drug Administration has approved first Gene Therapy for rare genetic disease affecting brain and nervous system in kids.

Lenmeldy (atidarsagene autotemcel) is the first FDA-approved gene therapy indicated for the treatment of children with pre-symptomatic late infantile, pre-symptomatic early juvenile or early symptomatic early juvenile metachromatic leukodystrophy (MLD).

Metachromatic leukodystrophy is a debilitating, rare genetic disease affecting the brain and nervous system. It is caused by a deficiency of an enzyme called arylsulfatase A (ARSA), leading to a buildup of sulfatides (fatty substances) in the cells. This buildup causes damage to the central and peripheral nervous system, manifesting with loss of motor and cognitive function and early death. It is estimated that MLD affects one in every 40,000 individuals in the United States. There is no cure for MLD, and treatment typically focuses on supportive care and symptom management.

“This is the first FDA-approved treatment option for children who have this rare genetic disease,” said Peter Marks, M.D., Ph.D., director of the FDA’s Center for Biologics Evaluation and Research (CBER). “We remain committed to advancing scientific and regulatory principles that enable the efficient development and review of safe, effective and innovative products that have the potential to change patients’ lives.”

Lenmeldy is a one-time, individualized single-dose infusion made from the patient’s own hematopoietic (blood) stem cells (HSCs), which have been genetically modified to include functional copies of the ARSA gene. The stem cells are collected from the patient and modified by adding a functional copy of the ARSA gene. The modified stem cells are transplanted back into the patient where they engraft (attach and multiply) within the bone marrow. The modified stem cells supply the body with myeloid (immune) cells that produce the ARSA enzyme, which helps break down the harmful build-up of sulfatides and may stop the progression of MLD. Prior to treatment, patients must undergo high-dose chemotherapy, a process that removes cells from the bone marrow so they can be replaced with the modified cells in Lenmeldy.

“MLD is a devastating disease that profoundly affects the quality of life of patients and their families. Advancements in treatment options offer hope for improved outcomes and the potential to positively influence the trajectory of disease progression,” said Nicole Verdun, M.D., director of the Office of Therapeutic Products in CBER. “This approval represents important progress in the advancement and availability of effective treatments, including gene therapies, for rare diseases.”

The safety and effectiveness of Lenmeldy was assessed based on data from 37 children who received Lenmeldy in two single-arm, open-label clinical trials and in an expanded access program. Children who received treatment with Lenmeldy were compared to untreated children (natural history). The primary efficacy endpoint was severe motor impairment-free survival, defined as the interval from birth to the first occurrence of loss of locomotion and loss of sitting without support or death. In children with MLD, treatment with Lenmeldy significantly reduced the risk of severe motor impairment or death compared with untreated children. All children with pre-symptomatic late infantile MLD who were treated with Lenmeldy were alive at 6 years of age, compared to only 58% of children in the natural history group. At 5 years of age, 71% of treated children were able to walk without assistance. Eighty five percent of the children treated had normal language and performance IQ scores, which has not been reported in untreated children. In addition, children with pre-symptomatic early juvenile and early symptomatic early juvenile MLD showed slowing of motor and/or cognitive disease.

The most common side effects of Lenmeldy are fever and low white blood cell count, mouth sores, respiratory infections, rash, medical line infections, viral infections, fever, gastrointestinal infections and enlarged liver.

After infusion with Lenmeldy, patients should be monitored for neutrophil counts and risk of delayed platelet engraftment until engraftment has been achieved. Treatment with Lenmeldy may be associated with formation of blood clots or a type of swelling of brain tissues known as encephalitis. There is a potential risk of blood cancer associated with this treatment; however, no cases have been seen in patients treated with Lenmeldy. Patients receiving this product should have lifelong monitoring for hematologic malignancies, including a complete blood count (with differential) annually and integration site analysis, as warranted, for at least 15 years after treatment.

The application received Priority Review, Orphan Drug, Rare Pediatric Disease and Regenerative Medicine Advanced Therapy (RMAT) designations.

The FDA granted approval of Lenmeldy to Orchard Therapeutics.

Powered by WPeMatico

Dupilumab treatment may improve work productivity in patients with atopic dermatitis: Study

Japan: A recent study published in Experimental Dermatology has shed light on the impact of 1-year treatment with dupilumab on work productivity in Japanese patients with atopic dermatitis (AD).

The researchers showed that Dupilumab improved work productivity in Japanese patients with atopic dermatitis. They stated that long-term remission of pruritus and improved quality of life (QoL) are important for comprehensive improvement of work productivity.

Atopic dermatitis (also called eczema) is a chronic (long-lasting) disease that causes redness, inflammation, and irritation of the skin. The condition places a burden on work productivity. Recently, dupilumab received approval for atopic dermatitis, but its impact on work productivity in Japanese patients has not been reported. Furthermore, data is limited on the effect of long-term treatment with dupilumab on work productivity.

To fill this knowledge gap, Masahiro Kamata, Department of Dermatology, Teikyo University School of Medicine, Tokyo, Japan, and colleagues investigated the activity and work productivity in Japanese patients with moderate-to-severe atopic dermatitis, utilizing the Japanese version of the Work Productivity and Activity Impairment (WPAI-AD-Japan) questionnaire. Further, they also examined the impact of dupilumab on work productivity.

The study included adult moderate-to-severe AD patients treated with dupilumab for more than 12 months from 2020 to 2022 who filled out the WPAI-AD-Japan questionnaire. Twenty-eight adult AD patients were analysed.

The study led to the following findings:

  • Absenteeism was low (mean: 5.3%), but presenteeism, work productivity loss and activity impairment were high (36.8%, 39.7%, and 48.9%, respectively).
  • Significant positive correlations were observed between work productivity loss and visual analogue scale (VAS) score of pruritus and between activity impairment and dermatology life quality index (DLQI).
  • Dupilumab treatment significantly reduced presenteeism, work productivity loss and activity impairment at 6 and 12 months.
  • The extent of their amelioration was numerically higher at 12 months than at six months.
  • The reduction rates in presenteeism, activity impairment, and work productivity loss were positively correlated with the reduction rates in DLQI and VAS score of pruritus at 12 months.

The findings showed that in Japanese AD patients, dupilumab improved work productivity.

“Long-term remission of pruritus and improved quality of life are important for comprehensive improvement of work productivity,” the researchers wrote.

Reference:

Sakurai, E., Kamata, M., Uchida, H., Okada, Y., Suzuki, S., Takeshima, R., Ito, M., Watanabe, A., Mizukawa, I., Egawa, S., Chijiwa, C., Hiura, A., Fukaya, S., Hayashi, K., Fukuyasu, A., Tanaka, T., Ishikawa, T., & Tada, Y. (2024). Impact of 1-year treatment with dupilumab on work productivity in Japanese patients with atopic dermatitis. Experimental Dermatology, 33(2), e15022. https://doi.org/10.1111/exd.15022

Powered by WPeMatico

COVID-19 Vaccines Effectively Protect Individuals with Psychiatric Disorders: Study

A recent study published in the Influenza Other Respiratory Viruses journal examined the effectiveness of COVID-19 vaccines across various psychiatric disorders yielded promising outcomes. This study by Matthew Levy  and team from the VISION Network in four US determined if mental health conditions influence the efficacy of mRNA COVID-19 vaccines.

The study encompassed data from a total of 2,436,999 adults from December 2021 to August 2022 and revealed that 22.1% of participants had at least one psychiatric disorder. Also, the individuals with psychiatric disorders expressed a higher incidence of COVID-19-related hospitalization compared to those without such conditions. Mood disorders, anxiety disorders and psychotic disorders were identified as significant independent predictors of hospitalization. Despite these increased risks, the mRNA vaccines demonstrated consistent effectiveness across all psychiatric disorder statuses.

Among the patients with any psychiatric disorder, recent mRNA vaccination significantly reduced the risk of hospitalization. The analysis showed adjusted hazard ratios of 0.35, 0.08 and 0.33 after the second, third and fourth doses, respectively when compared to the unvaccinated individuals. The corresponding vaccine effectiveness estimates were particularly robust that ranged from 65% to 92%, depending on the number of doses received. These figures closely mirrored the protection observed in patients without psychiatric disorders by highlighting the universal benefit of vaccination.

The study underscores the importance of vaccination in managing COVID-19 among the vulnerable populations with psychiatric disorders. Despite the elevated risk of hospitalization associated with mental health conditions, these findings reassure that mRNA vaccines offer reliable protection across diverse patient demographics. Overall, these findings suggest that despite psychiatric disorders increasing the risk of COVID-19-associated hospitalization, the vaccination remains as a powerful option in reducing this risk across all patient groups.

Reference:

Levy, M.E., Yang, D.-H., Dunne, M.M., Miley, K., Irving, S.A., Grannis, S.J., Weber, Z.A., Griggs, E.P., Spark, T.L., Bassett, E., Embi, P.J., Gaglani, M., Natarajan, K., Valvi, N.R., Ong, T.C., Arndorfer, J., Najdowski, M., Murthy, K., Ray, C., Tenforde, M.W. and Ball, S.W. (2024), Risk of COVID-19 Hospitalization and Protection Associated With mRNA Vaccination Among US Adults With Psychiatric Disorders. Influenza Other Respiratory Viruses, 18: e13269. https://doi.org/10.1111/irv.13269 

Powered by WPeMatico

Allogeneic stem cell therapy safe but fails to improve outcomes in acute ischemic stroke: JAMA

Japan: Findings from phase 2/3 TREASURE randomized clinical trial (RCT) that bone marrow-derived allogeneic stem cell therapy shortly after ischemic stroke was safe but failed to improve short-term outcomes. The findings were published online in JAMA Neurology on January 16, 2024.

In the RCT with 206 participants, intravenous (IV) administration of intravenous allogeneic multipotent adult progenitor cell (MultiStem) therapy within 18 to 36 hours of ischemic stroke onset was safe but did not improve short-term outcomes at 90 days compared with placebo. No grade 3 or 4 allergic reactions were observed, including in older patients.

“There was no significant difference in the rate of excellent outcomes — a composite of a modified Rankin Scale (mRS) score of 1 or below, a NIHSS score of 1 or less, and a Barthel index score (BI) of 95 or greater — between treatment and placebo groups (11.5% vs 9.8%; adjusted risk difference 0.5%),” the researchers reported.

However, exploratory subgroup analyses in patients with mRS scores of 0-2 at day 90 who were treated with the investigational MultiStem seemed to show better outcomes, particularly for patients with ischemic core volumes of 50 mL or more and those aged 64 or younger.

Cell therapy is touted as a promising treatment approach for stroke and other disease. However, there is no information on whether MultiStem (HLCM051), a bone marrow–derived, allogeneic, multipotent adult progenitor cell product, holds the potential for ischemic stroke treatment. Kiyohiro Houkin, Hokkaido University, Sapporo, Japan, and colleagues aimed to assess the safety and efficacy of MultiStem when administered within 18 to 36 hours of ischemic stroke onset.

For this purpose, 206 adults from academic and clinical centres in Japan who had an acute ischemic stroke (baseline NIHSS score of 8-20), an mRS score of 0 or 1 before stroke onset, and confirmed acute infarction involving the cerebral cortex and measuring more than 2 cm on the major axis, were included.

Patients with lacunar or brainstem infarction, those who received combined reperfusion therapy, and those with a change in NIHSS score of 4 or greater during a minimum period of 6 hours between screening and randomization were excluded.

The mean age of the participants was 76.5 years, and 54.4% were male. They received a single IV dose of allogeneic stem cell therapy or placebo for 30-60 minutes between 18 and 36 hours after stroke onset. Patient visits were scheduled at 7, 30, 90, and 365 days following randomization, with phone calls at day 60 and every 2 months after day 90.

The primary endpoints of the study were excellent and safety outcomes at day 90, measured as a composite of a mRS score of 1 or less, a NIHSS score of 1 or less, and a Barthel index score of 95 or greater. The secondary endpoints were excellent outcomes at day 365, mRS scores of 0 to 1 and 0 to 2 at day 90, and mRS score distribution at days 90 and 365.

The researchers reported the following findings:

  • The study included 206 patients (104 received MultiStem and 102 received placebo). Their mean age was 76.5 years, and more than half of patients were men (54.4%).
  • There were no between-group differences in primary and secondary endpoints.
  • The proportion of excellent outcomes at day 90 did not differ significantly between the MultiStem and placebo groups (11.5% versus 9.8%; adjusted risk difference, 0.5%).
  • The frequency of adverse events was similar between treatment groups.

“In this randomized clinical trial, IV administration of allogeneic cell therapy within 18 to 36 hours of ischemic stroke onset was safe but did not improve outcomes at 90 days,” the researchers wrote. However, efficacy was indicated in patients with large infarcts and possibly in younger patients based on exploratory subgroup analyses with no correction for multiple comparisons.

“To confirm the safety and efficacy of MultiStem therapy, the combined analysis of the TREASURE and ongoing MASTERS-2 trials will be conducted,” they concluded.

Reference:

Houkin K, Osanai T, Uchiyama S, et al. Allogeneic Stem Cell Therapy for Acute Ischemic Stroke: The Phase 2/3 TREASURE Randomized Clinical Trial. JAMA Neurol. Published online January 16, 2024. doi:10.1001/jamaneurol.2023.5200

Powered by WPeMatico

Guidewire during TAVR procedures appears to be efficacious and safe: Study

In a recent study, the SavvyWire, a 0.035-inch pre-shaped guidewire with unique pacing properties and a distal pressure sensor, has demonstrated remarkable efficacy and safety during transcatheter aortic valve replacement (TAVR) procedures. The study, conducted across eight European centers, aimed to assess the device’s performance and safety in patients with severe aortic stenosis undergoing TAVR. This study was published in the journal JACC: Cardiovascular Interventions by Ander R. and colleagues.

Continuous hemodynamic pressure monitoring is crucial during TAVR procedures, and the SavvyWire takes innovation to the next level by combining this feature with dedicated pacing properties. This prospective multicenter study delves into the device’s ability to achieve effective left ventricular rapid pacing runs and maintain safety throughout the procedure.

This prospective, multicenter clinical study enrolled 121 patients with severe aortic stenosis undergoing transcatheter aortic valve replacement (TAVR) across eight European centers. The participants, with a mean age of 82.2 ± 5.9 years and 50% women, were included in the study, with 119 ultimately treated with the SavvyWire. The primary efficacy endpoint focused on the device’s ability to induce effective left ventricular rapid pacing runs resulting in a significant systemic pressure drop below 60 mm Hg.

Key Findings:

  • High Efficacy: The primary efficacy endpoint was achieved in 98.3% of patients, showcasing the SavvyWire’s effectiveness in left ventricular rapid pacing runs.

  • Mean aortic systolic arterial pressure during rapid pacing: 46.6 ± 11.3 mm Hg.

  • Hemodynamic assessment with OptoMonitor 3 achieved in 99.2% of patients.

  • Safety First: The safety endpoint was achieved in 99.2% of patients, with no reported procedural mortality, stroke, or ventricular perforation.

  • Procedural Insights: The SavvyWire’s use could minimize interventions during TAVR procedures, offering significant systemic pressure drops and aiding in clinical decision-making post-transcatheter heart valve deployment.

The SavvyWire has emerged as a reliable and safe tool for TAVR procedures, demonstrating high efficacy in achieving effective left ventricular rapid pacing runs. This pioneering device not only enhances patient safety but also optimizes procedural outcomes, positioning itself as a valuable asset in the realm of transcatheter aortic valve replacement.

Reference:

Regueiro, A., Alperi, A., Vilalta, V., Asmarats, L., Baz, J. A., Nombela-Franco, L., Calabuig, A., Muñoz-García, A., Sabaté, M., Moris, C., Picard-Deland, M., Pelletier-Beaumont, E., & Rodés-Cabau, J. Safety and efficacy of TAVR with a pressure sensor and pacing guidewire. JACC. Cardiovascular Interventions,2023;16(24):3016–3023. https://doi.org/10.1016/j.jcin.2023.10.035

Powered by WPeMatico

New potassium channel blocker nasal spray may reduce severity of Sleep apnea, finds new research

Australian researchers have discovered that a new potassium channel blocker nasal spray at bedtime has the potential to reduce the severity of sleep apnea in people and lower their blood pressure.

The new research published in The Journal of Heart and Circulatory Physiology offers hope to millions of people around the world affected by sleep apnoea, a common and debilitating chronic respiratory condition.

“Obstructive sleep apnea (OSA) is a sleep disorder where the muscles in the back of the throat relax and the upper airway narrows or collapses, restricting oxygen intake and causing people to wake repeatedly throughout the night,” says Professor Danny Eckert, College of Medicine and Public Health.

“It has been linked to a variety of medical conditions including cardiovascular disease, stroke, obesity, diabetes, anxiety and depression.

“Treatment options are limited and while continuous positive airway pressure (CPAP) machines are a proven treatment for OSA, around 50 per cent of people struggle to tolerate them,” he says.

The aim of the study was to determine the effects of a new potassium channel blocker nasal spray on OSA severity and to investigate the potential influence of different breathing approaches such as restricted ‘nasal only’ breathing and the physiological characteristics of those who had a favourable response.

“Potassium channel blockers are a class of drugs that block the potassium channel in the central nervous system.

When used in a nasal spray, the blockers have the potential to increase the activity of the muscles that keep the upper airway open and reduce the likelihood of the throat collapsing during sleep,” says lead author Dr Amal Osman.

Using a randomised, blind trial, 10 people with OSA were given either the potassium blocker nasal spray, a placebo nasal spray or the potassium nasal spray in combination with restricted ‘nasal only’ breathing.

Seven out of the 10 people responded to the potassium channel blocker nasal spray showing a reduction in the frequency of upper airway collapsing episodes during sleep and lower blood pressure the next morning. The use of the spray with restricted ‘nasal only’ breathing did not improve quality of sleep in this trial.

“What we have discovered is that the nasal spray application of the potassium channel blocker that we tested is safe, well tolerated. Those who had a physiological improvement in their airway function during sleep also had between 25-45% reductions in markers of their OSA severity including improved oxygen levels as well as a reduction in their blood pressure the next day,” says Dr Osman.

“These insights provide a potential pathway for development of new therapeutic solutions for those people with OSA who are unable to tolerate CPAP machines and/or upper airway surgery, and those with a desire for alternatives to existing therapies,” says Professor Eckert.

“Right now, there are no approved drugs for treating OSA, but through these findings and future research we are getting closer to developing new and effective drugs that are safe and easy to use,” says Professor Eckert.

Reference:

Amal M. Osman,Barbara Toson,Ganesh R. Naik,Sutapa Mukherjee,Martina Delbeck, A novel TASK channel antagonist nasal spray reduces sleep apnea severity in physiological responders: a randomized, blinded, trial, The Journal of Heart and Circulatory Physiology, https://doi.org/10.1152/ajpheart.00541.2023.

Powered by WPeMatico

Rezafunginand caspofungin effective treatment option for invasive candidiasis

Rezafungin and caspofungin effective treatment options for invasive candidiasis suggest a new study published in the Lancet Infectious Diseases.

Rezafungin, a new US Food and Drug Administration-approved, long-acting echinocandin to treat candidaemia and invasive candidiasis, was efficacious with a similar safety profile to caspofungin in clinical trials. We conducted pooled analyses of the phase 2 STRIVE and phase 3 ReSTORE rezafungin trials.ReSTORE was a multicentre, double-blind, double-dummy, randomised phase 3 trial conducted at 66 tertiary care centres in 15 countries. STRIVE was a multicentre, double-blind, double-dummy, randomised phase 2 trial conducted at 44 centres in 10 countries. Adults (≥18 years) with candidaemia or invasive candidiasis were treated with once-a-week intravenous rezafungin (400 mg and 200 mg) or once-a-day intravenous caspofungin (70 mg and 50 mg). Efficacy was evaluated in a pooled modified intent-to-treat (mITT) population. Primary efficacy endpoint was day 30 all-cause mortality (tested for non-inferiority with a pre-specified margin of 20%). Secondary efficacy endpoint was mycological response. Safety was also evaluated. The STRIVE and ReSTORE trials are registered with ClinicalTrials.gov, NCT02734862 and NCT03667690, and both studies are complete.Findings: ReSTORE was conducted from Oct 12, 2018, to Oct 11, 2021, and STRIVE from July 26, 2016, to April 18, 2019. The mITT population, pooling the data from the two trials, comprised 139 patients for rezafungin and 155 patients for caspofungin. Day 30 all-cause mortality rates were comparable between groups (19% [26 of 139] for the rezafungin group and 19% [30 of 155] for the caspofungin group) and the upper bound of the 95% CI for the weighted treatment difference was below 10% (−1·5% [95% CI −10·7 to 7·7]). Mycological eradication occurred by day 5 in 102 (73%) of 139 rezafungin patients and 100 (65%) of 155 caspofungin patients (weighted treatment difference 10·0% [95% CI −0·3 to 20·4]). Safety profiles were similar across groups.Rezafungin was non-inferior to caspofungin for all-cause mortality, with a potential early treatment benefit, possibly reflecting rezafungin’s front-loaded dosing regimen. These findings are of clinical importance in fighting active and aggressive infections and reducing the morbidity and mortality caused by candidaemia and invasive candidiasis.

Reference:

Thompson GR 3rd, Soriano A, Honore PM, et al. Efficacy and safety of rezafungin and caspofungin in candidaemia and invasive candidiasis: pooled data from two prospective randomised controlled trials. Lancet Infect Dis. Published online November 23, 2023. doi:10.1016/S1473-3099(23)00551-0

Keywords:

Rezafunginand caspofungin, invasive candidiasis, treatment candidiasis, Thompson GR 3rd, Soriano A, Honore PM

Powered by WPeMatico

Novel GCGR/GLP-1R dual agonist survodutide effectively reduces HbA1c and body weight in type 2 diabetes: Phase 2 trial

Germany: A recent study published in Diabetologia has shed light on survodutide dose-response effects on body weight and HbA1c reduction, compared with placebo and open-label semaglutide in patients with type 2 diabetes (T2D).

Findings from the phase II randomized clinical trial showed a greater reduction in body weight and HbA1c levels after 16 weeks of treatment with survodutide, a dual glucagon/GLP-1 receptor agonist, compared with semaglutide and placebo in participants with type 2 diabetes. The study suggested that dose-related gastrointestinal adverse events (AEs) could be reduced with slower dose escalations.

“High-dose survodutide (≥1.2 mg twice weekly) reduced body weight ≥ 5% in >50% of participants and by ≥10% in >25% of participants,” Matthias Blüher, University of Leipzig and University Hospital Leipzig, Leipzig, Germany, and colleagues reported.

Glucagon-like peptide-1 receptor (GLP-1R) agonists are approved for treating type 2 diabetes and obesity. Glucagon receptor (GCGR) agonism can increase energy expenditure and lipolysis. GCGR/GLP-1R dual agonists can decrease body weight by reducing food intake and increasing energy expenditure and may be more effective than GLP-1R mono-agonists.

Against the above background, the research team aimed to assess the dose–response effects of the subcutaneous glucagon receptor/glucagon-like peptide-1 receptor dual agonist survodutide on HbA1c levels and bodyweight reduction. For this purpose, they conducted a Phase II, multicentre, randomised, double-blind, parallel-group, placebo-controlled study in clinical research centres.

The study assessed survodutide in participants aged 18–75 years, with T2D, an HbA1c level of 53–86 mmol/mol and a BMI of 25–50 kg/m2 on a background of metformin therapy.

Participants were randomized to receive survodutide (up to 0.3, 0.9, 1.8 or 2.7 mg once weekly [qw; dose group (DG) 1–4, respectively] or 1.2 or 1.8 mg twice weekly [DG 5 and 6, respectively]), placebo or semaglutide (up to 1.0 mg qw). Participants and all those involved in the trial conduct/analysis were blinded; the semaglutide arm was open-label.

Four hundred and thirteen participants were randomised (DG1, n=50; DG2, n=50; DG3, n=52; DG4, n=50; DG5, n=51; DG6, n=50; semaglutide, n=50; placebo, n=60). The full analysis set consisted of 411 treated participants (DG6, n=49; placebo, n=59).

The primary endpoint was an absolute change in HbA1c after 16 weeks of treatment from baseline. The key secondary endpoint was a relative change from baseline in body weight after 16 weeks of treatment.

The main findings of the study are as follows:

  • Adjusted mean HbA1c decreased from baseline (mean ± SD 64.7±9.2 mmol/mol [8.07±0.84%] after 16 weeks’ treatment: DG1 (n=41), −9.92 mmol/mol; DG2 (n=46), −15.95 mmol/mol; DG3 (n=36), −18.72 mmol/mol; DG4 (n=33), −17.01 mmol/mol; DG5 (n=44), −17.84 mmol/mol; DG6 (n=36), −18.38 mmol/mol.
  • The mean reduction in HbA1c was similar to low-dose survodutide (DG2: −15.95 mmol/mol; n=46) and semaglutide (−16.07 mmol/mol; n=45).
  • Mean bodyweight decreased dose-dependently up to −8.7% (DG6, n=37); survodutide ≥1.8 mg qw produced greater bodyweight reductions than semaglutide (−5.3%; n=45).
  • Adverse events were reported for 77.8% of survodutide-treated participants (mainly gastrointestinal), 52.5% receiving placebo and 52.0% receiving semaglutide.

“Despite the rapid dose escalation, no unexpected tolerability or safety concerns were raised, and importantly survodutide treatment produced greater HbA1c and bodyweight reductions than semaglutide 1.0 mg qw after 16 weeks of treatment,” the researchers wrote.

“The trial findings highlight the potential of the novel GCGR/GLP-1R dual agonist survodutide for non-alcoholic steatohepatitis (NASH), type 2 diabetes and obesity,” they concluded.

Reference:

Blüher, M., Rosenstock, J., Hoefler, J. et al. Dose–response effects on HbA1c and bodyweight reduction of survodutide, a dual glucagon/GLP-1 receptor agonist, compared with placebo and open-label semaglutide in people with type 2 diabetes: a randomised clinical trial. Diabetologia 67, 470–482 (2024). https://doi.org/10.1007/s00125-023-06053-9

Powered by WPeMatico

Very low calorie diets effective in adolescents with moderate to severe obesity, Australian study finds

Short-term very low calorie diets are safe for teenagers living with moderate to severe obesity when closely monitored by an experienced dietitian, new research to be presented at the European Congress on Obesity (ECO 2024), has found.

In addition, many of the adolescents who took part in the Australian study found a very low calorie diet to be an acceptable way to lose weight, despite experiencing side-effects.

Very low energy diets (VLED) typically involve taking in ≤ 800 calories per day and include meal replacements (bars and shakes) to ensure all essential nutrient requirements are met. VLEDs provide an alternative to weight loss treatment for young people who do not respond to conventional diet and exercise programmes and may be used instead of bariatric surgery as a means of transitioning to a healthy, balanced diet.

Although studies have shown that VLEDs can lead to rapid weight loss in young people, there is very little data on general side-effects (e.g. headache, fatigue, muscle cramps, constipation) and the acceptability of VLEDs in young people. There is also limited data on the impact of VLEDs on the growth, heart health and psychological wellbeing of young people and, as a result, some physicians have been reluctant to use them in this age group.

To learn more, Dr Megan Gow, of Children’s Hospital Westmead Clinical School, The University of Sydney, Westmead, Australia, and colleagues carried out a sub-analysis of data from Fast Track to Health, a 52-week study into the acceptability of different eating plans to adolescents with obesity.

Data from the first four weeks of Fast Track to Health, during which participants followed a nutritionally balanced VLED to kick-start their weight loss, was included in the sub-analysis.

141 (70 female) participants aged 13-17 years with obesity and at least one obesity-related complication, such as high blood pressure, insulin resistance or dyslipidaemia, consumed 800 calories a day from either 4 Optifast® formulated meal replacement products per day (shakes, soups, bars and/or desserts), with low carbohydrate vegetables (for example, broccoli, celery, capsicum, mushrooms and tomatoes) and 1 teaspoon of vegetable oil, or three Optifast® formulated meal replacements and one meal consisting of 100−150g lean, cooked meat, low carbohydrate vegetables and 1 teaspoon vegetable oil.

A dietician provided support at least weekly. Weight was recorded at baseline and week 4 and side-effects were recorded at day 3/4 and after 1, 2, 3 and 4 weeks. The adolescents also filled in a survey about how acceptable they found the VLED, including what they liked most and least.

Almost all the adolescents (134/141) completed the VLED (average age of 14.9 years, 50% male), despite side-effects being very common. Average weight loss was 5.5kg (12lb).

Nearly all (95%) experienced at least one side-effect during the VLED and most (70%) experienced at least three side-effects. Hunger, fatigue, headache, irritability, loose stools, constipation, nausea and lack of concentration were most common. Seven participants experienced viral infections.

Side-effects were most common at the end of week 1 and experiencing more side-effects at day 3-4 was associated with greater weight loss at the end of the 4 weeks, possibly indicating increased adherence to the VLED.

The adolescents rated the intervention 61/100 for “easy to follow” (easy = 100, difficult = 0) and 53/100 for “enjoyable to follow” (enjoyable = 100, not enjoyable = 0 points).

Losing weight (34% of participants) and the prescriptive structure (28% of participants) were the most-liked aspects of the VLED intervention. The restrictive nature (45% of participants) and taste of meal replacement products (20% of participants) were liked least.

The researchers conclude that a health professional-monitored VLED can be implemented safely in the short-term and, despite side-effects, is acceptable for many adolescents with moderate to severe obesity.

Dr Gow says: “More research is required to determine who would be most suited to a VLED. However, given the associated rapid weight loss, their use should be emphasised in clinical practice guidelines for the treatment of severe obesity and obesity-related complications in adolescents, especially before pharmacological or surgical intervention.

“Adolescents who are seeking treatment for their obesity should see their family doctor to discuss treatment options.”

Reference:

Very low calorie diets are safe and acceptable for teenagers with moderate to severe obesity when used short-term and supported by a dietitian, Australian study finds, European Association for the Study of Obesity, Meeting: European Congress on Obesity (ECO2024).

Powered by WPeMatico