Should Nutraceuticals be brought under CDSCO? Government forms panel to decide

New Delhi: The government has formed a panel to examine the possibility of bringing nutraceuticals under the ambit of the apex drug regulator CDSCO instead of the food regulator FSSAI to address regulatory challenges and promote consumer safety. Presently, the Food Safety and Standards Authority of India (FSSAI) regulates the usage of health supplements and nutraceuticals under the Food Safety and Standards (Health Supplements, Nutraceuticals, Food for Special Dietary Use, Food for Special Medical Purpose, and Prebiotic and Probiotic Food) Regulations, 2022.

This regulation covers food items that are specially processed or formulated for specific nutritional or dietary purposes, official sources said.
Nutraceuticals are products derived from food sources that are believed to provide extra health benefits besides the basic nutritional value found in foods
The sources said that the challenges in uniform implementation and enforcement, interchangeable usage of the same nutrient/ingredient at different doses for pharma and nutraceutical use and overlap in phylactic and therapeutic usage along with disease risk reduction claims were discussed with the Central Drugs Standard Control Organisation (CDSCO) officials in a recent meeting.
“Several issues were discussed following which a high-level committee under the chairmanship of Secretary, Ministry of Health has been constituted to review the regulatory challenges in nutraceutical and drugs to ensure consumer safety,” a source said.
The committee has as its members Secretary, Ministry of Ayush, Secretary, Ministry of Food Processing Industries, Secretary, Department of Pharmaceuticals, Chief Executive Officer (CEO), FSSAI, Drugs Controller General of India, Director General, Indian Council of Medical Research and Director General of Health Services (DGHS) as members.
The nutraceutical market in India is estimated to reach USD 18 billion by the end of 2025 as compared to USD 4 billion in 2020, according to industry data.
During the meeting some officials noted that many health supplements like probiotics, vitamins, minerals and botanicals also have therapeutic usage and due to unclear demarcation, many companies are shifting from CDSCO to FSSAI for approval of ingredients which are akin to drugs such as melatonin and zinc carnosine.
Some officials said several supplements are marketed with disease management/disease risk reduction claims considering that the same ingredients are permitted in both drugs and nutra regulations, the sources stated.
“Besides, there is no mandatory medical supervision for products covered under nutra regulations as a result people might consume it for longer duration and/or in higher doses which might prove harmful,” the sources said.
Officials said due to unsupervised usage of supplements, people at the same time consume supplements along with drugs which might interact with each other and may cause adverse effects on the health of the consumer.
Due to availability of health supplements over the counter there are chances of consuming multiple nutrients whose action might be antagonistic to each other like calcium from a multi-mineral supplement might affect the absorption of iron.
“The committee will identify the feasibility of regulating probiotic/prebiotic in food formats and drug formats. It will also examine if there is a need and possibility of bringing nutraceuticals and health supplements under the ambit of the CDSCO,” another official source said.
The panel will also explore the feasibility of price control for categories covered under nutraceutical regulations, besides, examining the feasibility of GMP provisions and certification for nutraceuticals and similar products in alignment with schedule M of drugs

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Jaslok Hospital doctors perform Automated Implantable Cardioverter Defibrillator implantation to treat rare heart disease

Mumbai: Jaslok Hospital and Research Centre in Mumbai achieved a remarkable breakthrough in treating an extremely rare heart disease that occurs in only 5 in 1,000,000 people in Asia. 

Mr. Raj Gorsa, a bank employee, experienced unusual symptoms such as chest pain, severe palpitations, and blackouts while working. On 10th November 2023, he was rushed to Jaslok Emergency Department. 

After a check-up and a series of tests, doctors identified that Raj had recurrent ventricular tachycardia, a potentially dangerous cardiac rhythm disorder. Despite initial attempts of treating him with medications, Raj’s condition did not improve. As a result, the Cardiac team decided to perform an Automated Implantable Cardioverter Defibrillator (AICD) implantation.

Also Read:Jaslok Hospital doctors treat 48-year-old woman with rare Ewing’s sarcoma of right breast

On further investigations to diagnose, it was discovered that Tuberculosis (TB), which is a common respiratory problem and Cardiac Sarcoidosis which is a rare inflammatory illness that affects the heart muscle, were the combined causes of Raj’s heart condition. Cardiac Sarcoidosis and Tuberculosis affecting the heart muscle can be a frequently missed diagnosis given its rarity and the high index of suspicion needed to make the diagnosis.

The Multidisciplinary Team’s combined effort of advanced Imaging specialists, Electrophysiologists, Interventional Cardiologists & Intensivists is often required to arrive at the precise diagnosis and plan optimal treatment to achieve disease control and halt the progression.

This Multidisciplinary Team at Jaslok Hospital was guided by Dr Ashwin Mehta (Director Cardiology ), and included Dr Rahul Chabbria ( Consultant Cardiology), Dr Upendra Bhalerao (Consultant Cardiovascular & Thoracic Surgery), Dr. Ameya Udayavar ( Consultant Electrophysiology) Dr Indraneel Raut (Addl. Director Critical Care Medicine) Dr Sadashiv Chaudhary (Consultant General, Bariatric & Laparoscopic Surgery) , Dr Rajashri Agaskar ( Consultant Cardiac Anaesthesia) , Dr Rushi Deshpande ( Director Nephrology- Academics ), Dr Vikarm Lele ( Director Nuclear Medicine). Dr. Nimish Shah (Consultant Chest Medicine ) and Dr Mala Kaneria ( Consultant Infectious Diseases ).

The Primary Cardiologist, Dr Rahul Chhabria mentioned “Myocardial tuberculosis is exceptionally rare forms of extra-pulmonary TB with few cases were reported world-wide. Sarcoidosis (CS) is multisystem granulomatous inflammatory disease with formation of non-caseating granulomas (lumps of proteins) of unknown aetiology. Sarcoidosis a rare heart disease that results from immune system to overreact causing lumps of tissues (granulomas) in the heart muscle.

Primary treatment for Cardiac Sarcoidosis is immunosuppression with corticosteroids with the goal of reducing inflammation and fibrosis, thereby preventing disease progression. Tuberculous Myocarditis is treated with combination of four anti TB drugs to achieve the disease control. Mr Raj was started on steroids and Anti TB drug treatment”

Mr. Raj continued to suffer from ventricular tachycardia and received multiple shocks from AICD to convert his heart rhythm to normal hence he was advised surgical options for controlling heart rate. He then underwent bilateral Thoracoscopic sympathectomy. This procedure involves cutting of the specific sympathetic nerves (the nerves that control the heart rate).

The procedure was done in this patient using Thoracoscopic Minimally Invasive Techniques. This is rare surgery which is a last resort to control heart rate that is done for life threatening ventricular arrhythmias receiving AICD shocks. The surgery was high risk as he had persistently abnormal heart rate. The Multidisciplinary team that looked after Raj’s periprocedural care ensuring an uneventful recovery was discharged hail and hearty on 27th November 2023. The team monitored his heart condition for 6 weeks to ensure that there are no heart rhythm disturbances affecting his daily life.

Dr Upendra Bhalerao, Consultant Cardiovascular and Thoracic Surgeon, the lead surgeon in Raj Gorsa’s case at Jaslok Hospital & Research Centre, Mumbai, expressed, “The successful treatment of Raj’s complex cardiac condition is a testament to the collaborative effort and dedication of our Clinical team. There was striking improvement in his heart rate and rhythm following this surgery and normalcy was restored”

Mr Jitendra Haryan, CEO at Jaslok Hospital & Research Centre, Mumbai, shared his views, saying, “With the constant efforts of our team, we are glad to provide quality treatment for the rarest cardiac conditions. We strive to improve with each passing day, and every patient that comes to Jaslok Hospital is treated with the utmost care and compassion.”

Expressing his gratitude, Raj Gorsa, the patient, stated, “I am happy to be alive and recovering now. My heart disease had turned my life upside down, and there were several touch-and-go moments when I would receive shocks to get my heart back in action. I owe a lot to the doctors and medical staff at Jaslok Hospital who persisted in their efforts to get my heart condition back to normal.”

Also Read:Mumbai: Jaslok Hospital services come to halt after nurse treating patient tests positive

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Study reveals alarming rise in the incidence of gastric outlet obstruction due to NSAIDs and opioid abuse in North West India

India: A recent study published in JAPI: Journal of the Association of Physicians of India has shed light on the alarming incidence of gastric outlet obstruction (GOO) related to nonsteroidal anti-inflammatory drugs (NSAIDs) and synthetic opioids in North West India.

Ashish Joshi, Professor, Department of Gastroenterology, Sardar Patel Medical College, Bikaner, Rajasthan, and colleagues observed an alarming rise in the incidence of GOO due to NSAIDs and opioid abuse at their centre. They stress making efforts to control the indiscriminate use of these over-the-counter drugs to prevent dreaded complications.

Gastric outlet obstruction is caused by obstruction of the pyloric channel or duodenum. It may be defined more specifically as the obstruction of the pylorus or pyloroduodenal area up to D2 (ampulla). The obstruction can be extrinsic or intrinsic to the duodenum and pylorus. The causes are mainly classified as benign or malignant.

The benign causes are corrosive ingestion, peptic ulcer disease (PUD), tuberculosis, NSAID, and opioid abuse. The most common cause of GOO in India is malignancy. PUD and corrosive ingestion are the common benign causes. NSAID intake in excessive doses or over a prolonged duration is known to cause ulceration of mucosa in the duodenum and stomach. NSAID and opioid abuse is a rare cause of GOO.

Dr. Joshi and the team conducted the study to know the incidence of nonsteroidal anti-inflammatory drugs (NSAIDs) and synthetic opioid abuse in cases of GOO.

They discussed the rising incidence of drug abuse containing synthetic opioid preparations like dextropropoxyphene or tramadol either in combination with NSAIDs like diclofenac or non-NSAID drugs like paracetamol in patients with gastric outlet obstruction.

The researchers conducted an observational study involving consecutive causes of GGO diagnosed from 2017 to 2019. A detailed history, including clinical examination and drug addiction history, was done. Investigations included routine biochemical and haematological tests, ultrasonography, upper gastrointestinal endoscopy (UGIE), rapid urease test (RUT), and histopathology of the diseased area.

Based on the study, the researchers reported the following findings:

  • Among the 102 cases diagnosed with GOO, 60.78% cases had a history of drug addiction.
  • The drug addiction history was as follows: NSAIDs and opioids in 56, opioids alone in four, and NSAIDs alone in two cases.
  • The most common site of stricture was the second part of the duodenum.
  • The features on histopathology were ulcerations of the mucosa infiltrated by eosinophils, plasma cells, and lymphocytes.

“The most common cause of GOO in our centre is NSAID and opioid addiction,” the researchers wrote.

“Due to abuse of NSAIDs along with opium, opium addicts are highly prone to duodenal ulcers. So, these patients should be evaluated for duodenal ulcers at the earliest suspicion to prevent further complications.”

“Legal efforts should be made to control the indiscriminate use of these over-the-counter drugs to prevent dreaded complications,” they concluded.

Reference:

Joshi A, Falodia S, Vyas A, et al. Alarming Incidence of Gastric Outlet Obstruction Related to NSAIDS and Synthetic Opioid in North West India. J Assoc Physicians India 2024;72(1):14–16.

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Moderate or severe traumatic brain injury tied to subsequent development of brain cancer in young veterans: JAMA

USA: A cohort study of more than 1.9 million veterans of the Afghanistan and Iraq wars showed that traumatic brain injury (TBI) is associated with the subsequent development of brain cancer. However, mild TBI was not associated with later brain cancer diagnoses. The findings were published online in JAMA Network Open on February 15, 2024.

Primary brain cancer is a relatively rare diagnosis that occurs in 7.02 per 100,000 persons in the US, and the prognosis is poor, with a 5-year survival of 35.7%. The most common brain cancer is glioblastoma, which is responsible for 50.1% of cases. Given the low incidence of this cancer form, the evidence is limited regarding potential risk factors.
To date, epidemiologic work examining the potential association of traumatic brain injury with the subsequent risk of brain cancer is conflicting. Further data may be useful. Considering this, Ian J. Stewart, Department of Medicine, Uniformed Services University of Health Sciences, Bethesda, Maryland, and colleagues aimed to examine whether a history of TBI exposure is associated with the subsequent development of brain cancer.
For this purpose, the research team conducted a retrospective cohort study from 2004 and 2019. The median follow-up for the cohort was 7.2 years. The study included Veterans Affairs (VA) and Department of Defense (DoD) administrative data on 1,919 740 veterans from the Long-Term Impact of Military-Relevant Brain Injury Consortium–Chronic Effects of Neurotrauma Consortium.
The main exposure of interest was traumatic brain injury severity (categorized as mild, moderate or severe [moderate/severe], and penetrating). The outcome of interest was the development of brain cancer.
The study led to the following findings:
· After 611 107 exclusions (predominately for no encounter during the study period), a cohort including 1,919 740 veterans was included, most of whom were male (80.25%). The median age at index date was 31 years.
· The cohort included 449 880 individuals with TBI (mild, 385 848; moderate/severe, 46 859; and penetrating 17 173).
· Brain cancer occurred in 318 individuals without TBI (0.02%), 80 with mild TBI (0.02%), 17 with moderate/severe TBI (0.04%), and 10 or fewer with penetrating TBI (≤0.06%).
· After adjustment, moderate/severe TBI (adjusted hazard ratio [AHR], 1.90) and penetrating TBI (AHR, 3.33), but not mild TBI (AHR, 1.14), were associated with the subsequent development of brain cancer.
“In the cohort study of post-9/11 era veterans, we found that moderate/severe TBI and penetrating TBI were associated with the subsequent development of brain cancer,” the researchers wrote.
While there was a small absolute number of brain cancer diagnoses, these diagnoses are tied to profoundly poor outcomes.
“Given that traumatic brain injury is a common injury incurred in the course of military service, further research of this rare but devastating condition is needed to better identify those at risk and develop screening protocols,” the research team concluded.
Reference:
Stewart IJ, Howard JT, Poltavskiy E, et al. Traumatic Brain Injury and Subsequent Risk of Brain Cancer in US Veterans of the Iraq and Afghanistan Wars. JAMA Netw Open. 2024;7(2):e2354588. doi:10.1001/jamanetworkopen.2023.54588

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Exoscope,a highly advanced technology with excellent Outcomes in Spinal Neurosurgery cases

The exoscope presents a viable substitute for the microscope in spine surgery cases. Spine surgeries are often lengthy and physically demanding, making it crucial to ensure surgeon comfort and confidence in the operating room. The exoscope can improve the surgical experience for all parties involved, including patients. However, the current literature on its effectiveness in spine surgery is limited.

According to a study published in World Neurosurgery, the exoscope demonstrated superiority in terms of shorter operative time, reduced blood loss, shorter hospital stay, and positive clinical outcomes compared to the operative microscope. They added that neurosurgeons should consider incorporating this ergonomically advanced visual technology in spinal surgeries.
Exoscope use in spinal neurosurgery offers promising surgical options by enhancing operative field visibility and ergonomics. Despite the benefits, there needs to be more data on its application in spine surgery in the literature. To compare the intraoperative outcomes, researchers conducted a retrospective review of spinal surgeries performed using an exoscope and an equal number of operative microscope cases by two senior surgeons at a single institution between 2016 and 2023. The analysis included demographic information, clinical presentation, surgical treatment, and operative outcomes.
Key findings from the study are:
· A total of 123 exoscope spinal surgeries were performed on 116 unique patients of a mean age of 67 ± 14 years, including 52% women.
· The microscope group included 126 surgeries on 120 unique patients with a mean age of 62 ± 14 years, with 45 % being women.
· Comparing the exoscope and microscope group, mean blood loss (28 mL vs. 132 mL), operative time (83 minutes vs. 103 minutes), and length of stay (1.04 days vs. 1.73 days) were less for the exoscope.
They said that using an exoscope in neurosurgical spine procedures led to shorter operation times, reduced blood loss, shorter hospital stays, and positive clinical results compared to the control group who underwent similar procedures with a microscope. Spine surgeons should consider incorporating the exoscope into their practice to enhance the operative experience and improve patient outcomes.
Reference:
Nawabi, N. L. et al. Intraoperative Performance with the Exoscope in Spine Surgery: An Institutional Experience. World Neurosurgery. https://doi.org/10.1016/j.wneu.2023.12.004

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Evidence of genetic correlation suggests causal relationship between hypothyroidism and rheumatoid arthritis

A recent study explored the intricate relationship between hypothyroidism and rheumatoid arthritis (RA). This research filled a crucial gap in understanding the shared genetic architecture between these debilitating conditions amidst the ongoing controversy surrounding their connection. The key findings of the study were published in the recent edition of Frontiers in Immunology journal.

This study was conducted by Zhifang Peng and team which involved a variety of advanced methodologies to dissect the genetic underpinnings of hypothyroidism and rheumatoid arthritis. This research utilized data from public genome-wide association studies and employed cutting-edge techniques like the linkage disequilibrium score regression, Mendelian randomization and transcriptome-wide association study.

The results from the analysis revealed a significant positive genetic association between hypothyroidism and RA within localized genomic regions. Also, the Mendelian randomization analysis pointed at a potential causal relationship that indicates at hypothyroidism which may contribute to the development of rheumatoid arthritis.

The research looked deeper by integrating gene expression data and identifying various tissues, including the spleen, lung and small intestine, where the genetic associations between the two conditions were strong. This comprehensive approach led to the identification of the major shared risk genes, including TYK2, IL2RA, and IRF5 that offers valuable insights into the biological mechanisms underlying both hypothyroidism and RA.

The investigation unveils a previously unrecognized genetic relationship between hypothyroidism and rheumatoid arthritis. This discovery enhanced our understanding of these complex diseases but also lays the groundwork for more targeted and effective interventions. The findings of this study holds promise for the future of precision medicine, giving way for tailored treatments that could address the shared genetic vulnerabilities of hypothyroidism and rheumatoid arthritis.

Reference:

Peng, Z., Huang, W., Tang, M., Chen, B., Yang, R., Liu, Q., Liu, C., & Long, P. (2024). Investigating the shared genetic architecture between hypothyroidism and rheumatoid arthritis. In Frontiers in Immunology (Vol. 14). Frontiers Media SA. https://doi.org/10.3389/fimmu.2023.1286491

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Bleach baths reduces atopic dermatitis symptoms and improves sleep quality

A recent study published in the Archives of Dermatological Research found strong evidence that bleach baths could efficiently help in the management of atopic dermatitis (AD). This controlled trial involved adults with atopic dermatitis to assess the impact of bleach baths on various aspects of the condition, including itch relief, skin barrier function and microbial composition. 

The participants in the trial were given instructions to take two bleach baths per week for a duration of 12 weeks, along with their regular treatments. The results showed that after the intervention period, over half of the AD subjects underwent a significant reduction in AD severity that was measured by the Eczema Area and Severity Index (EASI).

This study revealed marked improvements in itch severity and quality of life among the AD patients, with 87% reporting enhanced sleep quality which is often compromised by the relentless itching associated with the condition. Also, the bleach baths also demonstrated benefits for skin barrier function. The participants saw improvements in transepidermal water loss (TEWL) and stratum corneum (SC) integrity which indicates enhanced skin barrier function that is crucial in managing AD symptoms.

While the bleach baths showed promise in reducing AD symptoms and improving skin barrier function, this study observed no significant effects on the microbial composition of the skin, particularly regarding Staphylococcus aureus (S. aureus). These findings underscore the comprehensive nature of AD treatment and highlight the potential of bleach baths as an adjunct therapy for managing the condition.

Reference:

Stolarczyk, A., Perez-Nazario, N., Knowlden, S. A., Chinchilli, E., Grier, A., Paller, A., Gill, S. R., De Benedetto, A., Yoshida, T., & Beck, L. A. (2023). Bleach baths enhance skin barrier, reduce itch but do not normalize skin dysbiosis in atopic dermatitis. In Archives of Dermatological Research (Vol. 315, Issue 10, pp. 2883–2892). Springer Science and Business Media LLC. https://doi.org/10.1007/s00403-023-02723-1

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Can Psychological care delivered over phone effectively combat loneliness and depression?

The study, led by a team based at the University of York and Hull York Medical School and at Tees, Esk and Wear Valleys NHS Foundation Trust, found levels of depression reduced significantly and the benefits were greater than those seen for antidepressants.

Participants in the study reported their levels of emotional loneliness fell by 21% over a three-month period and the benefits remained after the phone calls had ceased, suggesting an enduring impact.

The Behavioural Activation in Social Isolation trial (BASIL+ trial) started within months of the 2020 pandemic and was the largest trial ever undertaken to target and measure loneliness in this way. The study, published in the journal The Lancet (Healthy Longevity), represents a rapid advance in evidence to understand what works in preventing loneliness.

People invited to take part in the BASIL+ study were aged over 65 with multiple long-term conditions. They had been asked to shield during COVID and were at a high risk of loneliness and depression.

The trial was supported by a £2.6M award from the National Institute for Health and Care Research (NIHR) and was the only mental health trial prioritised by the NHS as part of its Urgent Public Health programme – a cornerstone of its fight against COVID. Hundreds of older people were recruited to the trial from 26 sites across the UK during the COVID pandemic of 2020-21.

Politicians and policy makers have become increasingly aware of the importance of loneliness, but have struggled to know “what works” in its prevention. The World Health Organization has just declared loneliness to be a ‘Global Health concern’ and has launched an international commission on the problem. It is anticipated that the results of the BASIL+ trial will feed into this process, since BASIL+ is the largest trial ever undertaken to combat loneliness. The Jo Cox Commission, established in memory of the murdered politician, estimates that 9 million people are affected by loneliness in the UK and there is a cross governmental strategy to tackle loneliness, with a Ministerial appointment.

The research was jointly led by Professor Simon Gilbody from the University of York and Hull York Medical School and Professor David Ekers from Tees, Esk and Wear Valleys NHS Foundation Trust. Professor Gilbody said: “We now know that loneliness is as bad for your health as smoking 15 cigarettes a day and depression is a silent killer. All of us working on the BASIL+ trial had older parents and relatives who became socially isolated during lockdown.”

“Based on our previous research, we had a good idea what might work”, Professor Ekers added. “With the support of the NHS and the NIHR we were able to test this in a large rigorous trial. The results are now available and this is very exciting. The UK led the world with the vaccine discovery trials. Similarly in mental health we have advanced the science of ‘what works’ in the area of loneliness, and we have learned much from the dark days of the pandemic.’”

Professor Ekers, Honorary Professor at the Mental Health and Addictions Research Group at the University of York and Professor Dean McMillan, Professor of Clinical Psychology at Hull York Medical School and University of York designed and led the telephone support programme. Professor McMillan said “an ounce of prevention is worth a pound of cure, and this trial shows how we can prevent both depression and loneliness”.

Professor Lucy Chappell, CEO of the National Institute for Health and Care Research, which funded the study, said: “These results are an important step forward in understanding what works in tackling and preventing loneliness and depression. The research is also a great example of how public money allows researchers, healthcare professionals and the public to work together across institutions and organisations to deliver results that will really make a difference to people’s health and wellbeing.”

Dr Liz Littlewood, the BASIL+ trial manager from the Department of Health Sciences, University of York, added: “This is what the UK does well and it shows how the NHS, Universities and third sector organisations were able to work in partnership during the pandemic to tackle the big health challenges.”

Reference:

Prof Simon Gilbody, Elizabeth Littlewood, Dean McMillan, Lucy Atha, Della Bailey, Kalpita Baird, Behavioural activation to mitigate the psychological impacts of COVID-19 restrictions on older people in England and Wales (BASIL+): a pragmatic randomised controlled trial, The Lancet Healthy Longevity, https://doi.org/10.1016/S2666-7568(23)00238-6,

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Lobeglitazone could be promising insulin sensitizer for management of type 2 diabetes in India: SENSITIZE INDIA

India: Findings from a randomized, double-blind, phase III SENSITIZE INDIA trial have revealed the safety and efficacy of lobeglitazone 0.5 mg once daily for treating type 2 diabetes mellitus (T2DM) in the Indian population.

The study, published in JAPI: Journal of the Association of Physicians of India, showed that lobeglitazone significantly improved glycemic parameters and was noninferior to pioglitazone; hence, considered a promising insulin sensitizer in type 2 diabetes management in India.

“The mean change from baseline in HbA1c percentage in the lobeglitazone 0.5 mg group was noninferior to that in the pioglitazone 15 mg group,” the researchers reported. There were no major safety concerns. Lobeglitazone was well-tolerated and safe.

The study confirmed the safety and efficacy of lobeglitazone 0.5 mg in the Indian population.

Glycemic control is the primary goal of T2D treatment. Several orally administered glucose-lowering agents have been developed for diabetes treatment. Metformin, with its good glucose-lowering efficacy and acceptable safety profile, remains the first-line low-cost treatment option for the majority of patients. However, a large number of patients with type 2 diabetes have inadequately controlled diabetes despite treatment with metformin and require an additional glucose-lowering agent.

The primary pathophysiological flaw in type 2 diabetes is insulin resistance, and the only class of antidiabetic medications that address insulin resistance exclusively is thiazolidinediones (TZD).

The efficacy and safety of lobeglitazone sulfate, a thiazolidinedione that works by activating PPAR-α/γ dual agonist, has been reported only in the Korean population, and no study has been conducted in India. Considering this, Shashank Joshi, Lilavati Hospital and Research Centre, Mumbai, Maharashtra, India, and colleagues aimed to evaluate the efficacy and safety of lobeglitazone sulfate 0.5 mg once daily in comparison with pioglitazone 15 mg once daily in subjects with type 2 diabetes with inadequate glycemic control on metformin (≥1500 mg/ day). For this purpose, they performed a 16-week randomized, double-blind, and multicenter study.

It included 328 subjects with type 2 diabetes with ≥7.5% glycated haemoglobin (HbA1c) ≤10.5% and on stable metformin dose. They were assigned to both the treatment arms. The study’s primary outcome was a mean change in HbA1c.

Safety assessments included home-based glucose monitoring, adverse events (AE), vital parameters, electrocardiogram (ECG), and laboratory assessments.

The study led to the following findings:

  • There was a statistically significant reduction in HbA1c at week 16 in the lobeglitazone group with the least square (LS) mean change of 1.01.
  • The LS mean difference between the two groups was 0.05, which was statistically significant.
  • There were statistically significant reductions in fasting and postprandial glucose.
  • Treatment-emergent adverse events (TEAE) were comparable between both groups.

“This trial, the first on lobeglitazone in Indian patients, revealed that lobeglitazone was just as effective as pioglitazone (15 mg) in treating metformin-uncontrolled T2D in Indian patients without posing a significant risk to safety,” the research team wrote.

“Lobeglitazone was found to be noninferior to pioglitazone concerning change in fasting insulin, HOMA-β, and HOMA-IR; hence, it may be a promising insulin sensitizer for diabetes management in India,” they concluded.

Reference:

Joshi S, Tandon M, Kodgule R, et al. Randomized, Double-blind, Phase III Trial of Lobeglitazone Add-on to Metformin in Type 2 Diabetes (SENSITIZE INDIA). J Assoc Physicians India 2024;72(1): 32–42

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Systolic BP Variability powerful determinant of CV outcome; amlodipine may render long-term benefit: confirms ASCOT trial

UK: Systolic blood pressure variability (SBPV) is a strong predictor of cardiovascular (CV) outcomes, even in those with controlled systolic blood pressure (SBP), according to the ASCOT trial.

The findings, published in the European Heart Journal, highlight the importance of SBPV as an additional marker of CV risk and affirm the superiority of amlodipine versus atenolol on BP measurements and clinical outcomes. During the trial period, the long-term benefits of amlodipine-based treatment compared with atenolol-based treatment in reducing cardiovascular events appear to be primarily mediated by an effect on systolic BPV.

Based on the findings, the researchers suggest considering visit-to-visit systolic BPV as a new paradigm for risk assessment in hypertensive patients.

Previous studies have shown visit-to-visit BPV to be an important predictor of CV outcomes. However, there is no clarity on the long-term effect of a period of blood pressure control with differential BPV.

Ajay Gupta, William Harvey Research Institute, Queen Mary University of London, UK, and colleagues extended the Morbidity and mortality follow-up of UK participants in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure-Lowering Arm for up to 21 years to determine the CV impact of mean SBP control and BPV during the trial, and amongst those allocated to atenolol- and amlodipine-based treatment.

The study included eight thousand five hundred and eighty hypertensive participants. 4305 were assigned to amlodipine ± perindopril-based and 4275 to atenolol ± diuretic-based treatment during the in-trial period of a median of 5.5 years and were followed for up to 21 years, using linked hospital and mortality records.

A subgroup of participants comprising 2156 patients was followed up to six years after the trial closure with a self-administered questionnaire and a clinic visit. In-trial mean systolic blood pressure and standard deviation of visit-to-visit SBP as a measure of BPV were measured using >100 000 BP measurements.

The risk hazard ratios (HRs)], associated with (i) mean with SBP and BPV during the in-trial period, for the CV endpoints occurring after the end of the trial and (ii) randomly assigned treatment to events following randomization, for the first occurrence of pre-specified CV outcomes were determined using Cox proportional hazard models.

The study led to the following findings:

  • Using BP data from the in-trial period, in the post-trial period, although mean SBP was a predictor of CV outcomes (HR per 10 mmHg, 1.14), systolic BPV independent of mean SBP was a strong predictor of CV events (HR per 5 mmHg 1.22) and predicted events even in participants with well-controlled BP.
  • During a 21-year follow-up, those on amlodipine-based compared with atenolol-based in-trial treatment had significantly reduced risk of total CV events [HR 0.93], stroke [HR 0.82], atrial fibrillation [HR 0.91], and total coronary events [HR 0.92], with weaker evidence of a difference in CV mortality [HR 0.91].
  • There was no significant difference in the incidence of nonfatal myocardial infarction and heart failure, fatal coronary heart disease, and all-cause mortality.

Based on current guidelines, contemporary clinical practice, dictates that treatment decisions in hypertensive patients are determined by SBP and DBP levels. “Our studies, however, provide robust evidence that visit-to-visit BPV is a far more powerful determinant of CV outcome and that at least half of all CV events in our cohort occurred in those with controlled BP but high BPV,” the researchers wrote.

The study also confirms the long-term benefits of amlodipine-based treatment in lowering the risk of coronary events, stroke, and all CV events.

“Future studies will determine whether visit-to-visit systolic BPV should be a new target for therapeutic interventions,” the research team concluded.

Reference:

Gupta, A., Whiteley, W. N., Godec, T., Rostamian, S., Ariti, C., Mackay, J., Whitehouse, A., Janani, L., Poulter, N. R., Sever, P. S., Aldegather, J., Collier, D., Delles, C., Dyker, A., Eaton, M., Heller, S., Kristinsson, A., Lip, G., MacGregor, G., . . . Webster, J. Legacy benefits of blood pressure treatment on cardiovascular events are primarily mediated by improved blood pressure variability: The ASCOT trial. European Heart Journal. https://doi.org/10.1093/eurheartj/ehad814

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