Year: 2021

Categories : CancerTags :

Study Discovers How Melanoma Cells Hide From Immune System

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Melanomas in some patients do not respond well to immunotherapy treatments, and now researchers have discovered that a defect in STING gene expression in melanoma cells helps them escape immune cell surveillance.

Cancer cells use a variety of recently discovered mechanisms to avoid detection and destruction by immune cells, including defective detection and destruction of T cells, losses in expression of critical proteins on tumour cells and defective cell signaling in both immune and tumor cells.

The interferon signaling pathway is an important signaling pathway in interactions between tumour and immune cells. This pathway increases expression of molecules allowing tumour cells to be targeted by immune cells. One of the interferon signaling pathway’s key molecules is STING, which is activated by the protein cGAS.

Previously Moffitt researchers showed that STING activity is suppressed and altered in a subset of melanomas, rendering tumour cells invisible to the immune system.

Using a process called epigenetic modification to turn genes on or off with methylation groups, the researchers sought to improve the understanding of alterations in STING signaling in melanoma and find out how STING expression is suppressed. 

The researchers performed a series of laboratory experiments and discovered that the DNA regulatory region of the STING gene is highly modified by methylation groups resulting in loss of STING gene expression in certain melanoma cell lines. Importantly, they confirmed these findings in patient clinical samples of early and late-stage melanomas and showed similar methylation events and loss of expression of the upstream STING regulator cGAS.

The researchers demonstrated the possibility of reactivating STING and/or cGAS expression with a demethylating drug or genetic approaches. These successfully reactivated STING activity, resulting in increased interferon levels when triggered by STING agonist drugs that enabled the melanoma cells to now be recognised and targeted by immune cells.

“These studies show the critical importance of an intact STING pathway in melanomas for optimal T cell immunotherapy success, and how to overcome a notable STING defect in melanoma cases of gene hypermethylation by a combination therapy,” said senior author James J. Mulé, PhD, and Associate Center Director, Translational Science, H. Lee Moffitt Cancer Center & Research Institute.”Unless patients’ melanomas are pre-screened for intact versus defective STING, it is not at all surprising that clinical trials of STING agonists have, to date, uniformly failed.”

Source: News-Medical.Net

Journal information: Falahat, R., et al. (2021) Epigenetic reprogramming of tumor cell–intrinsic STING function sculpts antigenicity and T cell recognition of melanoma. Proceedings of the National Academy of Sciences. doi.org/10.1073/pnas.2013598118.

Categories : Diet and NutritionTags :

Low Fat Diets Reduce Testosterone

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A new study has found that low fat diets decrease men’s testosterone levels by 10-15%, with important considerations for health.

Optimal testosterone levels are a crucial part of men’s health, with higher risks of heart disease, diabetes, and Alzheimer’s disease resulting from low levels of the hormone. Healthy testosterone levels are also key for men’s athletic performance, mental health, and sexual health. Clinically low testosterone rates are referred to as hypogonadism.

Men’s testosterone levels have been falling since the 1970s but low risk dietary strategies could be a useful treatment for low testosterone.

In a systematic review and meta-analysis, the researchers analysed the results of six well-controlled studies with a total of 206 participants. Men were first put on a high fat diet (40% fat), and then switched to a low fat diet (20% fat), with testosterone levels decreasing by 10-15% on average. Particularly bad were vegetarian low fat diets causing decreases in testosterone up to 26%.

Previous studies conducted in humans and mice found that high intakes of monounsaturated fats found in olive oil, avocados, and nuts may boost testosterone production. However, omega 6 polyunsaturated fats predominantly found in vegetable oils, may in fact damage the cells’ ability to produce testosterone. This is because highly unsaturated fats such as polyunsaturated fats are more prone to oxidation, causing damage to the cells.

“Low testosterone levels are linked to a higher risk of heart disease, diabetes, and Alzheimer’s disease.”

More research needs to be done in this area, said the researchers.

“Ideally, we would like to see a few more studies to confirm our results. However, these studies may never come, normally researchers want to find new results, not replicate old ones. In the meantime, men with low testosterone would be wise to avoid low fat diets.” said lead researcher Joseph Whittaker.

A controversial topic in nutritional science, dietary fibre has proponents of various diets often in stark disagreement over low fat versus low carbohydrates. Low fat diets have benefits such as reduced cholesterol levels, which should be weighed up against the potential downsides, such as decreased testosterone levels.

Traditionally, dietary guidelines have focused on limiting fat intake, with the current UK and US guidelines limiting fat intake to less than 35% of total calories. However, as more research on the benefits of high fat, low carbohydrate diets is done, this traditional view is coming under increasing scrutiny. Recent research has shown that high fat diets can decrease triglycerides, decrease blood pressure, increase HDL cholesterol (aka ‘good cholesterol’), and now it was found that it can increase testosterone levels.

Source: News-Medical.Net

Journal information: Whittaker, J & Wu, K (2021) Low-fat diets and testosterone in men: Systematic review and meta-analysis of intervention studies. The Journal of Steroid Biochemistry and Molecular Biology. doi.org/10.1016/j.jsbmb.2021.105878.

Categories : Diseases, Syndromes and ConditionsTags :

Discovery Offers New Treatment for Sickle Cell Anaemia

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In a promising step towards a new treatment for sickle cell anaemia, researchers have discovered a small molecule that boosts levels of foetal hemoglobin, a healthy form that adults normally do not make.

Current treatment options are few, including bone marrow transplants and gene therapy, and only address a subset of symptoms. Opioids are used for pain management, with their hazard for addiction and abuse.
The researchers presented their results at the spring meeting of the American Chemical Society (ACS).

“Using our proprietary small molecule probe and CRISPR guide RNA libraries, we screened a disease-relevant cell model that allowed us to pinpoint a treatment target,” said Ivan V Efremov, PhD, senior director, head of medicinal chemistry of Fulcrum Therapeutics.

Sickle cell disease occurs when genes for two of haemoglobin’s four proteins contains an error, resulting in a rigid, sickle-like shape. This has consequences in reduced oxygen transport, and painful blockages of the irregularly shaped cells called vaso-occlusive crises. The red blood cells die fast, leading to anaemia. These patients are also at high risk of developing stroke, heart disease, kidney failure and other potentially deadly conditions.

While in the womb, humans make “foetal” haemoglobin that carries oxygen normally but three or four months after birth, cells switch to an adult haemoglobin version. Although the adult haemoglobin expressed by sickle cell patients is defective, stem cells in their bone marrow still have the capacity to produce foetal haemoglobin.

Some individuals have a hereditary persistence of foetal hemoglobin, and so tap this resource automatically. “They have the sickle cell mutation, but additional mutations result in continued expression of fetal hemoglobin into adulthood,” said Christopher Moxham, PhD, chief scientific officer of Fulcrum Therapeutics. With foetal hemoglobin levels of around 25-30%, he said, enough red blood cells function well enough that patients may become asymptomatic.

The team developed a drug, called FTX-6058, that mimics the effect seen in patients with the hereditary persistence of foetal hemoglobin. It attaches to a protein inside bone marrow stem cells that will mature into red blood cells and reinstates their foetal haemoglobin expression. “What is really key is FTX-6058 upregulates fetal hemoglobin across all red blood cells, a pancellular distribution,” Dr Efremov said. “If some red blood cells did not express this, they could still sickle and cause disease symptoms.” Fulcrum began a phase 1 safety trial in healthy adult volunteers last year after preclinical experiments showed an increase in fetal hemoglobin levels to around 25-30%.

“What distinguishes FTX-6058 is that we are targeting the root cause of sickle cell disease,” Dr Moxham said. “Other drugs approved in this space, particularly since 2019, are treating the disease’s symptoms, either the anemia or the vaso-occlusive crises.”

Preclinical experiments showed that FTX-6058 outperformed another foetal heamoglobin booster, hydroxyurea, approved in the 1990s.

A phase 2 clinical trial is planned for people living with sickle cell disease which should begin by the end of 2021. The researchers are also further characterising the therapeutic molecule. Fulcrum is also considering exploring the use of FTX-6058 in people living with β-thalassemia, a blood disorder in which haemoglobin production is reduced.

Source: Medical Xpress

Categories : CancerTags :

High Melanoma Rates Reported in Sunny US State

On By ModernMedia

A study reports that melanoma mortality among people in Utah, a sunny, high-altitude state, outpaced that of the rest of the country over 1975 to 2013.

This runs counter to the falling melanoma death rates in recent years in both Utah and the United States, a trend likely due to improved treatments such as immunotherapy. It is still the deadliest skin cancer type, with melanoma diagnosis rate in Utah the highest in the US.

Motivation for the research was recent evidence showing that for most of the 1990s and 2000s, even as melanoma mortality in the United States remained constant, incidence increased six-fold. This increasing incidence without accompanying mortality rise indicates overdiagnosis, ie false cancer diagnoses. 

In the case of melanoma, overdiagnosis may result from increased scrutiny, where increasing numbers of biopsies may find a benign lesion that would have gone undetected.

Since Utah has the highest melanoma incidence, a team from Huntsman Cancer Institute (HCI) at the University of Utah set out to evaluate the state’s melanoma diagnosis and death rate data. Biostatistician Kim Herget analysed data from the Utah Cancer Registry, a National Cancer Institute Survival, Epidemiology, and End Results (SEER) database, and the researchers found that in contrast to the rest of the country, melanoma mortality in Utah rose 0.8% per year from 1975 to 2013. Even though Utah’s melanoma death rates have been falling in recent years, they are still higher than the rest of the country.

“Although we agree that overdiagnosis of melanoma is a growing problem, the sustained increase in melanoma mortality in Utah suggests that at least some fraction of the increasing incidence is real and cannot be attributed solely to overdiagnosis,” said Doug Grossman, MD, PhD, who co-leads the HCI melanoma and skin cancer centre at HCI and serves as professor of dermatology at the University of Utah. “Our research underscores an increased risk for Utahns, and so we must remain vigilant about melanoma. For doctors, this means regular conversations with patients about their skin health and family history. For patients, this means practicing sun-safe behaviors like diligent sunscreen use, wearing sun-protective clothing, and monitoring their skin at home on a monthly basis to reduce risk of skin cancer and optimize early detection.”

Future studies should determine whether this trend in people living in Utah results from increased ultraviolet exposure in a mostly fair-skinned population living in a sunny, high-altitude climate or if it is associated with other factors such as environment or genetics. Melanomas are also found at higher rates in immune compromised patients.

Source: Medical Xpress

Journal information: Doug Grossman et al, The Rapid Rise in Cutaneous Melanoma Diagnoses N Engl J Med 2021; 384:e54 DOI: 10.1056/NEJMc2101980

Categories : COVID General InterestTags :

Liquor Industry Questions Alcohol Ban Effectiveness

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Representatives from the liquor industry have said that the South African government must consider data from a new report that shows little alcohol ban effectiveness on trauma cases. However, other studies show negative effects of alcohol during lockdown, and a surge in violent trauma in Cape Town after alcohol bans were lifted.

In a statement on Thursday, the South African Liquor Brand owners Association (Salba) referenced a new report showing that, compared to other countries, South Africa saw similar trauma cases with its lockdown and alcohol ban to those that only had a lockdown.

The report had financial support from Distell, led by independent data expert Ian McGorian of Silver Fox Consulting, in collaboration with professor Mike Murray from the University of KwaZulu-Natal.

The report found that trauma cases in South Africa under lockdown dropped 60%. But other countries also saw the same drop with no alcohol ban, including the UK (57%), Ireland (62%), Italy (56.6%) and the USA (54%), casting doubt over the effectiveness of alcohol bans in curbing trauma. The researchers also commented that curfews may have explained more of a reduction in trauma cases than alcohol bans.

While members of the liquor industry recognised the impact of alcohol on South African society, they said that government needs to be more objective with its lockdown regulations.

Salba chairperson Sibani Mngadi said the alcohol ban over Easter Weekend, while simultaneously allowing larger gatherings, made even less sense in reducing COVID transmission. This suggests that government was not considering science in its decision making, he said.

However, a multicentre study from Colorado, USA showed that even while trauma cases during lockdown fell by 33%, alcohol screens increased from 34% to 37%, and alcohol positive patients rose from 32% to 39%.

A study of Cape Town trauma admissions saw a dramatic drop of 53% in trauma admissions during the hard lockdown and an immediate rebound coinciding with the resumption of alcohol sales, with a 107% increase in gunshots wounds compared to pre-lockdown conditions.

The researchers noted that in South Africa the trauma demographic is much younger, with much higher rates of violence, with about half of homicide victims in SA testing positive for alcohol.

Distell chief executive Richard Rushton said the industry was merely asking that the data should be viewed objectively to improve dialogue with decision makers.

“We are all on the same side, and we want to help find solutions. We are very clear that alcohol abuse is unacceptable and causes harm. Our view is that the focus must be on finding ways to deal with high-risk drinkers, rather than using blunt instruments that penalise all South Africans.

“Any proposed new regulations need to be evidence-based, rational and target problem areas,” he said.

Business Leadership SA chief executive Busisiwe Mavuso said that lockdown could have been better managed, as 220 000 jobs had been lost along billions of rands in tax to the fiscus, while uncertainty still plagued alcohol producers.

“The decisions made to confront the health crisis should not have unintended consequences for the economy, and that is exactly what has happened with the bans on alcohol,” she said.

Mr Mavuso added that, since the start of the pandemic, business has been a willing partner to government and “needs to be part of the solution to ensure we fight this pandemic with the least possible damage to the economy”.

“The data analysis by the alcohol industry is an important intervention and must be taken seriously as we move forward.”

Source: BusinessTech

Categories : Mental HealthTags :

Ambivalent Results for ‘SlowMo’ Digital Psychosis Therapy

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A digital cognitive behavioral therapy for psychosis called SlowMo did not result in significant improvements for those suffering from paranoia, although it had other benefits.

“The therapy was engaging, and over 80% of participants completed all therapy sessions,” Philippa Garety, PhD, of King’s College London, wrote in an email to MedPage Today. “It is at least as effective as longer, more complex psychological treatments for paranoia, which are generally more challenging to deliver and frequently not available in clinical services.”

Garety herself was surprised by some of the study’s results, specifically the lack of improvements in some areas at the 24-week follow-up point. She said her team was also surprised — and pleased — to see that SlowMo was “equally effective across our wide demographic, of differing ages, gender, and ethnicities,” she wrote.

Some of the trial’s results surprised her, specifically the lack of improvements in some areas at the 24-week follow-up point. But her team was also pleased to see that it was equally effective across a wide demographic.

The study recruited 361 eligible adult participants from three UK community mental health services, and were randomised 1:1 to usual care only or to usual care plus SlowMo, which consisted of eight digitally supported face-to-face sessions and a mobile app .

The researchers saw improvements at the halfway point for both aspects of the 32-item Green et al. Paranoid Thoughts Scale (GPTS), which includes social reference (Part A) and persecution  (Part B). At the end of the trial, SlowMo did have a significant effect on Part B of the GPTS, but not on Part A.

Positive secondary outcomes were seen in observer-rated measurements, at a 12-week follow-up in Psychotic Symptom Rating Scales (PSYRATS) Delusion subscale and belief flexibility, as well as at 24 weeks. SlowMo did significantly affect the rate at which patients jumped to conclusions.

Dr Garety and co-authors noted that limitations including not controlling for time spent with therapists, as well as treatment as usual being used as the comparator.

Katherine Newman-Taylor, of University of Southampton in England, a psychologist focussing on patients with psychosis, said that the initial results are hopeful.

“This study shows that belief flexibility and worry are key therapeutic targets when working with people struggling with distressing paranoia,” Newman-Taylor told MedPage Today in an email. “As psychological therapists, we need to consider how people think, as well as what they think, when seeking to understand distressing psychosis and support individuals’ recovery.”

“In this trial, we have demonstrated, for the first time in a large randomized controlled trial, that helping people to slow down their thinking reduces paranoia in everyday life, and improves quality of life and wellbeing,” Dr Garety told MedPage Today.

Source: MedPage Tooday

Journal information: Garety P, et al “Effects of SlowMo, a blended digital therapy targeting reasoning, on paranoia among people with psychosis” JAMA Psychiatry 2021; DOI: 10.1001/jamapsychiatry.2021.0326.

Categories : COVIDTags :

Smartphone Tracking in COVID Shows Movement Linked to Case Rise

On By ModernMedia

According to a new study which used mobility tracking of cell phone data, a greater movement of people is a strong predictor of increased COVID cases rates.

Until people are widely vaccinated against SARS-CoV-2, the array of nonpharmaceutical public health interventions such as physical distancing and limiting travel and social contacts will remain the most effective means of controlling COVID. Capturing the interrelationship between human behaviour and infectious diseases is one of the hardest problems in epidemiology.

“Mobility measures capturing human activity through anonymized tracking of smartphones are believed to be reasonable proxies of contact rates outside of one’s own home; these measures can provide more timely and reliable sources of information on contact rates compared with time-use surveys or contact tracing,” the authors wrote.

Researchers looked at anonymised smartphone mobility data from nearly 12 months from March 2020 to March 2021, both at a national and provincial level, while controlling for date and temperature. A 10% increase in the mobility of Canadians outside their homes was found to be associated with a 25% increase in subsequent SARS-CoV-2 weekly growth rates. They investigated at the mobility threshold (the level needed to control the virus) and the mobility gap (the difference between the threshold and actual movement).

“The mobility threshold and mobility gap can be used by public health officials and governments to estimate the level of restrictions needed to control the spread of SARS-CoV-2 and guide, in real-time, the implementation and intensity of nonpharmaceutical public health interventions to control the COVID-19 pandemic,” wrote the authors.

Source: News-Medical.Net

Journal information: Brown, K. A., et al. (2021) The mobility gap: estimating mobility thresholds required to control SARS-CoV-2 in Canada. Canadian Medical Association Journal. doi.org/10.1503/cmaj.210132.

Categories : General InterestTags :

‘Absolutely Revolutionary’ Kaftrio Drug Betters Lives of Cystic Fibrosis Patients

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In an article by the BBC, one woman with cystic fibrosis recounts how the “absolute revolutionary” Kaftrio drug has improved her life.

Jody Lewis, 31, is an avid rider and one of around 80 people in Wales to have had Kaftrio, a “revolutionary” drug treatment for cystic fibrosis, at Liverpool Heart and Chest Hospital.

Cystic fibrosis is a genetic condition resulting in faulty cystic fibrosis transmembrane conductance regulator (CFTR) proteins which regulate the transfer of chloride ions into and out of the cells. The condition causes thick, sticky mucus to build up in the lungs, gastrointentinal system and other organs.

The treatment is suitable for around 90% of CF patients aged 12 and over and has been approved for use in the UK. Kaftrio is a triple combination of elexacaftor, tezacaftor which corrects the faulty CFTR protein, and  ivacaftor, which potentiates CFTR. 

Ms Lewis, said since taking it she had “a whole future and life” ahead of her.
Her condition worsened about two and a half years ago, when she was put on continuous oxygen supply, needing four or five oxygen bottles a day, almost placed on a ventilator and considered for a lung transplant. This meant stopping riding and changing how she cared for her four dogs.

“I’d have to change my complete lifestyle just to survive. I get that I’d have a second chance at life but it wouldn’t be me, it wouldn’t be true to who I am,” she said. At her worst, she said she could barely cope with simple tasks such as making tea.

This all changed when she started taking Kaftrio last year.

“Within a week, my [oxygen saturation] was going up and up to 94, 96 and I wasn’t even on oxygen and I can’t remember the last time I saw those numbers, it was mad.

“I’m now as good as I was back when I was 25, so I’ve like regained six years of my life,” she said.

“When I was 25 I was fine, I was in work, living a normal life, so it’s given me all that back really,” she said, adding that it was “really emotional” and “fantastic” to be able to ride her horse again after two and a half years..

“I’ve got a whole future and life in front of me that I’ve never had to think about.”

Consultant Martin Ledson, clinical lead for respiratory medicine at Liverpool Heart and Chest Hospital, described the drug treatment as “absolutely revolutionary”, saying that it had changed the lives of 222 of the hospital’s patients.

He said that when his patients were born, they could expect to live to their 30s, so they have “lived all their lives with the knowledge that their life expectation could be 30 or even less”.

“What this drug does is extend that life expectancy who knows how long?

“Not only that, the patients immediately – within 24 hours – feel amazingly better. Their breathing tests improve, they get less chest infections, their digestion improves, they put on weight and in many cases need to take less treatment,” he said.

Source: BBC News

Categories : CancerTags :

Most Glucose Consumption in Non-cancer Cells, Upending Century-old View

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A study has found that cancer cells are not the main consumers of glucose in tumours, challenging an observation held for over a century.

“The field of cancer metabolism has really exploded over the last 20 years, but it has been based on this observation that Otto Warburg published in 1922—that cancer cells can consume glucose at a very high rate,” said Jeffrey Rathmell, PhD, Cornelius Vanderbilt Professor of Immunobiology and director of the Vanderbilt Center for Immunobiology. “We now know that tumors include many types of cells, and it’s surprising that non-cancer cells are actually the major glucose consumers in the tumor.”

One application of the Warburg effect is where cancer cells are picked out based on their glucose metabolism in positron emission tomography (PET), a radioactive tracer of glucose (FDG). However, this doesn’t always yield the results expected by clinicians.

“I had been curious about why PET scans are ‘hot’ or ‘not hot’ for many years because the kidney cancer type that I study, from what we understand about the biology, should light up hot on PET and often doesn’t,” said W. Kimryn Rathmell, MD, PhD, Hugh J Morgan Professor and Chair of the Department of Medicine. “Jeff and I have had many conversations about which cells are using the glucose: is it the cancer cells; is it the immune cells; how does it all fit together? You can just imagine our dinner table.”

A pair of MD-PhD students from their labs, Bradley Reinfeld and Matthew Madden, decided to resolve this conundrum. They administered two different PET tracers (one for glucose, one for glutamine) to mice with tumours, isolated the tumors and separated them into various cell types and then measure the radioactivity in the cells. Six different tumour models were used, including colorectal, kidney and breast cancer. The results showed that, in each case, myeloid immune cells (primarily macrophages) had the highest uptake of glucose, followed by T cells and cancer cells. Cancer cells, in contrast, had the highest glutamine uptake.

“We think this is a general phenomenon that extends across cancer types,” Madden said.

The researchers showed that, instead of limiting nutrients, certain cellular signaling pathways drove the differences in glucose and glutamine uptake. The prevailing view is rather of metabolic competition taking place in the tumour microenvironment, where the cancer cells “win” to deplete nutrients and suppress immune cells.

“The idea has been that the cancer cells are gobbling up all of the glucose, and consequently, immune cells can’t get enough glucose and can’t do their job,” Madden said. “Our data suggest that nutrients aren’t limiting. Instead, cells are programmed to consume certain nutrients, and there is partitioning of nutrients between cells: cancer cells pick up glutamine and fatty acids; immune cells pick up glucose.”

Knowing that cells in the tumour microenvironment use different nutrients “may allow for specifically targeting particular cell types—for new therapies or for imaging people’s tumors,” Reinfeld said.

Kimryn Rathmell added, “We’re in a good place now to be able to have more sophisticated PET radiotracers. It’s time to think about testing fluoridated glutamine or other nutrient probes in patients.”

The study’s findings also have implications for interpreting FDG-PET imaging results, she said. “We order FDG-PET scans all the time, and we need to have a good sense of what that information is providing us. We use it to judge tumor response, but it may be telling us about inflammatory response and not tumor response.”

Source: Medical Xpress

Journal information: Cell-programmed nutrient partitioning in the tumour microenvironment, Nature (2021). DOI: 10.1038/s41586-021-03442-1

Categories : Cardiovascular DiseaseTags :

New Clinical Practice Review for Diabetes Drugs

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A new clinical practice review article in The New England Journal of Medicine (NEJM) collates the latest trial results and guidelines into a systematic approach for the treatment of patients with diabetes and a risk of cardiovascular disease. It is the journal’s first such review by the journal in nearly a decade.

Clinical practice reviews differ from research studies in that they present a common clinical problem along with the evidence supporting various treatment strategies and review the guidelines. Finally, the author offers clinical recommendations for optimising patient care.

Compared to those without the disease, people with type 2 diabetes have over double the risk of developing atherosclerotic cardiovascular disease and heart failure. In South Africa, 10.1% of the population over 15 is believed to have type 2 diabetes, and is expected to cost the health sector R35.1 billion by 2030. 

The NEJM article by Johns Hopkins Medicine endocrinologist and associate professor Rita Rastogi Kalyani, MD, presents an up-to-date approach for health care providers when choosing among glucose-lowering therapies for their patients with diabetes, particularly to reduce the risk of cardiovascular disease. Dr Kalyani reviews the cardiovascular benefits and risks of the most common diabetes drugs currently available on the US market.

“We’ve seen a major shift in diabetes care over the past few years,” said Dr Kalyani. “We now have tools to better understand how to reduce both microvascular and macrovascular complications in people with type 2 diabetes.”

Dr Kalyani highlighted specific agents in two newer drug classes, which she showed are beneficial for patients with diabetes who already show signs of heart or blood vessel disease.

The glucagon-like peptide 1 (GLP-1) receptor agonists liraglutide, injectable semaglutide and dulaglutide increase insulin production from the body, particularly after meals.

Sodium glucose cotransporter 2 (SGLT2) inhibitors empagliflozin and canagliflozin reduce the amount of glucose the body re-absorbs through urine. 

All of these are effective in risk reduction for major cardiovascular events, such as heart attack or stroke. The SGLT2 inhibitor dapagliflozin is effective in reducing the risk of hospitalisation for heart failure.

“After metformin, which is widely considered the initial drug treatment for type 2 diabetes, specific drugs in the GLP-1 receptor agonist and SGLT2 inhibitor classes with demonstrated cardiovascular benefit should be considered as additional medications for patients who already have cardiovascular disease. This should be done irrespective of whether their A1C level is at target to reduce the risk of future cardiovascular events,” advised Kalyani.

The A1C test measures the average percentage of glucose in a person’s haemoglobin over the span of several months. Healthy A1C levels are below 5.7%, and typically, A1C levels over 6.5% indicate diabetes.

Newer drugs tend to be costlier, and long-term effects are unknown. Also, prior to 2008, the US Food and Drug Administration did not require large outcome trials for drugs after they were released onto the market, meaning that older drugs have less certain cardiovascular outcomes, said Dr Kalyani.
The NEJM article details specific drugs that offer additional benefits for patients with diabetes who have conditions such as multiple cardiovascular disease risk factors, heart failure and chronic kidney disease.

“Some agents such as dulaglutide and dapagliflozin also have demonstrated cardiovascular benefit in patients with multiple cardiovascular risk factors,” said Dr Kalyani.

Further, specific SGLT2 inhibitors can be beneficial for patients who have heart failure with reduced ejection fraction, as well for patients with chronic kidney disease.

Comprehensive drug tables in the article take into account factors for consideration in clinical practice when choosing a glucose-lowering drug for patients with type 2 diabetes, including A1C-lowering efficacy, route and frequency of administration, cost, impacts weight, hypoglycaemia risk, side effects and clinical benefits.

“Health care providers in primary care, endocrinology, cardiology and nephrology are now prescribing these newer glucose-lowering drugs for their patients,” Dr Kalyani said. “Diabetes care will need to be increasingly collaborative in the future and, at its core, remain patient-centered.”

Source: Medical Xpress

Journal information: Rita R. Kalyani et al. Glucose-Lowering Drugs to Reduce Cardiovascular Risk in Type 2 Diabetes, New England Journal of Medicine (2021). DOI: 10.1056/NEJMcp2000280