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22nd April 2024
Semaglutide could be beneficial in helping to treat patients with type 2 diabetes and obesity-related heart failure, a study has shown.
In a trial of more than 600 patients with obesity-related heart failure with preserved ejection fraction and type 2 diabetes, semaglutide led to several benefits after one year.
This included larger reductions in heart failure-related symptoms and improvement in physical limitations, researchers reported in the New England Journal of Medicine (NEJM).
It follows previous research suggesting benefit of the glucagon-like peptide-1 (GLP-1) receptor agonist in obesity-related heart failure in people without type 2 diabetes, the researchers said.
But it was not clear if the same would be true of those who also had type 2 diabetes for several reasons including that they tend to present with more advanced disease and are already likely to be receiving treatment with a sodium-glucose cotransporter-2 inhibitor for their heart disease.
After 12 months, the researchers reported that a once-weekly 2.4mg dose of semaglutide not only led to a larger reduction in heart failure symptoms in this group but also increased the six-minute walk distance.
It was also associated with fewer serious adverse events than placebo, the researchers noted.
But the trial was not designed to evaluate the number of hospitalisations or urgent doctor visits for heart failure symptoms, they added.
Those taking semaglutide lost more weight compared with placebo, but the weight reduction was 40% lower than reported in people with heart failure but not diabetes in a previous study.
Writing in the NEJM, the researchers concluded that the findings suggested ‘the mechanisms of benefit with semaglutide may extend beyond weight loss’.
This could be due to the effects of the drug on the heart and blood vessels, inflammation, insulin resistance and other factors, they said.
The consistency between the findings of this and the previous trial in patients without type 2 diabetes ‘provides greater reassurance that semaglutide is an efficacious treatment option with a favourable safety profile in a broad population of patients with obesity-related heart failure,’ they said.
Commenting on the study results, Professor Naveed Sattar, professor of cardiometabolic medicine at the University of Glasgow, said: ‘This new well conducted trial suggests once again we have underestimated the impact of excess weight in the development of heart failure with preserved ejection fraction.
‘Preventing obesity remains critically important but newer treatments that help people living with obesity lose decent amounts of weight could help improve the lives of many living with heart failure, and many other conditions associated with obesity.
‘Robust randomised trials are needed to also ensure these drugs are not only beneficial but also safe and the evidence here is also mounting and reassuring.’
Earlier this month, a review by the European Medicine Agency’s Pharmacovigilance Risk Assessment Committee concluded that available evidence does not support a causal association between GLP-1 and suicidal and self-injurious thoughts and actions.
A version of this article was originally published by our sister publication Pulse.
11th August 2023
Semaglutide has been found to reduce the risk of major adverse cardiovascular events (MACE) by 20% in overweight or obese adults, its manufacturer Novo Nordisk has claimed.
According to headline results from the SELECT study, the anti-diabetic drug semaglutide was able to cut the risk of overweight or obesity experiencing a MACE by 20% compared to placebo.
This randomised, double-blind, placebo-controlled trial, the results of which are yet to be published in a peer-reviewed journal, was designed to evaluate the efficacy of semaglutide 2.4 mg versus placebo, as an adjunct to standard of care, for the prevention of MACE, in overweight or obesity with no prior history of diabetes.
The primary endpoint of the study was defined as the composite outcome of the first occurrence of MACE defined as cardiovascular death, non-fatal myocardial infarction or non-fatal stroke.
Commenting on the findings, Martin Holst Lange, executive vice president for development at Novo Nordisk, said: ‘People living with obesity have an increased risk of cardiovascular disease but, to date, there are no approved weight management medications proven to deliver effective weight management while also reducing the risk of heart attack, stroke or cardiovascular death. Therefore, we are very excited about the results from SELECT showing that semaglutide 2.4 mg reduces the risk of cardiovascular events.‘
He added: ‘SELECT is a landmark trial and has demonstrated that semaglutide 2.4 mg has the potential to change how obesity is regarded and treated.‘
SELECT enrolled 17,604 adults across 41 countries at more than 800 investigator sites and was initiated in 2018.
All participants had pre-existing cardiovascular disease, including a prior myocardial infarction (76.3%) or stroke (23.3%). In addition, enrolled participants were aged ≥45 years with a body mass index (BMI) ≥27 kg/m2.
In total 1,270 first MACEs accrued. The trial achieved its primary objective by demonstrating a statistically significant and superior reduction in MACE of 20% for people treated with semaglutide 2.4 mg compared to placebo. In the trial, semaglutide 2.4mg appeared to have a safe and well-tolerated profile in line with previous semaglutide 2.4mg trials.
Naveed Sattar, professor of metabolic medicine at the University of Glasgow, said: ‘More details are needed on the trials to give it proper consideration, including examination of safety aspects, but even here the top line report also sounded optimistic.
‘The one thing to caution is we do not know to what extent the weight loss effects of semaglutide as opposed to its other direct effects on blood vessels or the heart, account for the 20% reduction in cardiovascular events, and more data are needed to try to work this out.‘
For now, however, this is a good result for patients, especially as progressively more are living with obesity and cardiovascular disease.‘
Novo Nordisk expects to file for regulatory approvals of a label indication expansion for semaglutide 2.4 mg in the US and the EU later in 2023. The detailed results from SELECT will also be presented at a scientific conference later in the year.
In March, NICE recommended Wegovy for use as part of a patient’s treatment for obesity in an NHS specialist weight management service and with the support of a multi-disciplinary team.
29th June 2023
The UK Government’s latest scheme to increase access to the anti-diabetic drug semaglutide is designed to reduce levels of obesity and related complications. But past evidence suggests it is doomed to fail. Clinical writer Rod Tucker finds out more.
A two-year pilot scheme, backed by investment up to £40m, is to be launched in the UK to increase accessibility to the anti-obesity treatment semaglutide outside of hospital settings.
Obesity is a leading cause of conditions such as cardiovascular disease, diabetes and cancer, and was reported to be a factor in more than one million admissions to NHS hospitals in 2019/20. According to information released by the Department of Health and Social Care, obesity has an annual cost to the NHS of £6.5bn.
On the face of it, the rationale for widening access to the anti-diabetic treatment appears sensible. Any approach that leads to a reduction in the level of obesity should give rise to a commensurate decrease in the number of individuals developing obesity-related conditions and requiring interventions such as knee and hip replacements. If obesity levels drop, so would the waiting list for these complications. Its a win-win situation.
But there are two other relevant considerations. Firstly, does wider access to semaglutide align with current recommendations for the drug, and secondly, how likely is it that the pilot scheme will be successful?
In March 2023, NICE recommended semaglutide as an option for weight management in adults, alongside a reduced-calorie diet and increased physical activity. However, there were several caveats attached to this recommendation.
Firstly, use of the drug was restricted to a maximum of two years and it could only be prescribed at a specialist weight management service. Secondly, patients were required to have at least one weight-related comorbidity and body mass index (BMI) of at least 35.0 kg/m2, although patients could access the drug if they had a BMI of 30.0 kg/m2 to 34.9 kg/m2 and met the criteria for referral to specialist services.
By broadening access to semaglutide, the pilot scheme is therefore at variance to the NICE guidance. While NICE is sponsored by the Department of Health and Social Care, and purported to be independent of the UK Government, it has been argued that the organisation is not, and indeed cannot be, truly independent of the Government.
To date, NICE has remained silent on the Government’s latest initiative, probably because it goes against everything that was outlined in its draft guidance. The Government has argued that its latest scheme is merely a pilot project to explore if and how the anti-diabetic drug can be made safely available outside of a hospital settings. This will happen, it says, alongside NHS England’s work to implement NICE’s recommendations to make this new class of treatment available to patients through established specialist weight management services.
The evidence for semaglutide is convincing, but it is important to acknowledge that the drug only works when used as an adjunct to diet and exercise. Moreover, it is likely to require life-long use despite the two year restriction imposed by NICE. It is now clear that significant weigh re-gain occurs once patients stop taking the anti-diabetic drug, and another study shows how mean body weight increased by 6.9% after cessation of treatment.
A further barrier to the potential success of the pilot scheme is the growing recognition that obesity is a complex condition and that hypothalamic neuro-inflammatory responses play an important role. As a result, obesity management requires a multi-interventional approach.
Commenting on the pilot scheme, the UK health and social care secretary Steve Barclay said: ‘This next generation of obesity drugs have the potential to help people lose significant amounts of weight when prescribed with exercise, diet and behavioural support.’
But how effective is a primary-based weight management service likely to be? An insightful analysis of GP and nurse practitioner habits in response to a mock scenario, makes for interesting reading. Published in 2020, the study found that overall only 24% of respondents would refer patients to a weight management service. The most common response, in over 80% of cases, was to provide either diet or exercise-based advice.
Despite this, evidence from the US offers some hope that behaviour-based weight-loss interventions, either with or without weight loss medications, result in more weight loss than usual care conditions.
The potential for greater access to an effective anti-diabetic weight-loss drug is to be welcomed. Nevertheless, it can only ever serve to address the consequences and not the root causes of obesity. A huge amount of evidence also makes it abundantly clear that obesity is inextricably linked to socioeconomic and demographic factors. Overweight and obesity are far more prevalent in deprived areas, in those of black ethnicity and in the least well educated. In fact, someone living in the most deprived area is nearly twice as likely to be obese as someone in the least deprived area.
With past behaviour seen as the best predictor of future behaviour, the evidence over the last 30 years does not augur well for the current pilot scheme. A recent analysis has shown how obesity policy in England has involved 14 strategies, published from 1992 to 2020, which contain 689 wide-ranging policies. The authors suggested that the continued failure to reduce the prevalence of obesity in England for almost three decades may be due to either weaknesses in the policies’ design, or to failures of implementation and evaluation.
Obesity represents a growing problem, with 25.9% of adults in England obese and 37.9% overweight. Moreover, we live in an obesogenic environment that is influenced by the availability and affordability of foods, together with varying access to opportunities for physical activity. Consequently, it is perhaps too simplistic to label obesity as an individual’s problem: obesity is an environmental problem that requires a wholesale change with regulatory interventions directed at reducing intake of ultra-processed food and acknowledgement of the impact of socioeconomic factors. Such a change requires additional funding, and considerably more that the currently allocated £40m.
Greater access to the anti-diabetic drug semaglutide is unlikely to single-handedly solve the problem of obesity. Nonetheless, if provided through an adequately funded weight management services as part of a comprehensive package that includes behavioural support, access to exercise facilities and nutritional advice, it might have a noticeable effect on levels of obesity and its health-related consequences.
28th June 2023
Retatrutide gave rise to substantial reductions in body weight in adults with obesity, according to a recent phase 2, randomised placebo-controlled trial.
Retatrutide (formerly LY3437943) is an agonist for the glucagon-like peptide 1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP) and glucagon (GCG) receptors. In a phase 1b trial, the drug was shown to produce robust reductions in glucose and bodyweight. In addition to drugs such as semaglutide, it is being explored as a treatment for weight loss.
Continuing to explore the value of the drug, in a recent phase 2 trial published in the New England Journal of Medicine, researchers undertook a double-blind, randomised, placebo-controlled trial in adults with a body mass index (BMI) of 30 or more, or those with a BMI of 27 but with at least one weight-related condition.
The trial randomised participants to subcutaneous retatrutide at doses of 1 mg, 4 mg, 8 mg and 12 mg or placebo, administered once weekly for a total of 48 weeks. The primary endpoint was the percentage change in body weight from baseline to week 24, and researchers also assessed the safety of the drug.
In addition to treatment, all the participants received a lifestyle intervention, including regular counselling sessions delivered by a dietitian or qualified healthcare professional.
A total of 338 participants with a mean age of 48.2 years (48% female) were enrolled and randomised to the different doses or placebo.
After 24 weeks of treatment, weight loss ranged from -7.2% in the 1 mg group through to -17.5% in the 12 mg group, compared to -1.6% in the placebo group. However, at week 48, weight loss increased to -24.2% in the 12 mg group compared to -2.1% in the placebo arm. In addition, at week 48, among those receiving 12 mg of retatrutide, 26% of participants had a body-weight reduction of 30% or more.
Treatment with retatrutide also improved cardiometabolic measures including systolic and diastolic blood pressure, glycated haemoglobin, fasting glucose, insulin and lipids – except for high-density lipoprotein. Furthermore, improvements in blood pressure within the 48-week treatment period resulted in discontinuation of at least one antihypertensive medication in 30% of the participants in the 12 mg group.
Adverse events were reported in 70% of the placebo participants and in 73-94% of retatrutide patients. They were highest in the 8 and 12 mg groups. Serious adverse events occurred in 4% of the retatrutide placebo groups.
27th June 2023
A higher dose of adalimumab is likely to be more effective for obese patients with hidradenitis suppurativa, according to the findings of a small trial.
Adalimumab (ADA) is one of only two biologic therapies, together with secukinumab, approved by the EMA for the management of hidradenitis suppurativa (HS). However, adalimumab dosing is not weight-based and in two phase 3 trials, just over half of the patients assigned to adalimumab 40 mg/week (ADA40) achieved a clinical response.
Given that patients with HS are four times more likely to be obese compared to the general population, there might be an advantage of using a higher ADA dose in HS patients who are either overweight or obese.
In the current study, published in the Journal of Drugs in Dermatology, a team of US researchers evaluated the effectiveness of adalimumab 80 mg/week (ADA80) versus 40 mg, in overweight and obese patients with moderate to severe HS. The team included patients with a body mass index greater than 25 and who were refractory to treatment with ADA40. A dose of 80 mg was administered for at least three months and improvements were assessed using the HS-Physician Global Assessment.
A total of eight patients with a mean age of 37 years (six females) and with a median body mass index of 36.6 were included in the study and were followed for a median of 13.2 months on ADA80.
Patients experienced a greater improvement in the HS-Physician Global Assessment with ADA80 compared to ADA40 (p = 0.01). In addition, all five patients who had their lesion counts documented achieved a HS clinical response, and all eight patients reported improvements in pain, drainage, lesions and the frequency of disease flares.
While acknowledging the limitations from a small sample size, the researchers suggested that their data indicates a benefit increasing the dose of adalimumab in overweight and obese patients with HS.
Earlier this year, a phase 3 trial found bimekizumab to be an effective treatment for patients with hidradenitis suppurativa.
5th June 2023
Anti-diabetic drug lead to weight loss, providing a much needed impetus in the fight against the rising global obesity epidemic, but are these drugs the ultimate solution? Rod Tucker investigates.
According to recent data released by Boehringer Ingelheim and Zealand Pharma, their novel glucagon/GLP-1 receptor dual agonist, BI 456906, designed as an anti-diabetic medicine, gave rise to a 14.9% weight loss in those either obese or overweight compared with placebo.
Though not yet commercially available, BI 45609 is likely to join a long list of anti-diabetic treatments being used in the fight against obesity. Such innovations are urgently needed given the inexorable rise in global levels.
For example, a recent report from the World Obesity Federation described how in 2020, an estimated 2.6 billion people globally had a body mass index (BMI) greater than 25 and therefore classed as overweight. This figure is projected to rise to four billion by 2035.
Obesity therefore represents a major public health concern, especially given how it is associated with as many as 18 co-morbidities including cardio-metabolic disorders and several types of cancer.
The pharmacological management of obesity has always been challenging, with the currently available anti-obesity medications often delivering insufficient efficacy. Part of the problem has been unravelling the complex hormonal milieu that exists in obese individuals and which hormones to target with drugs.
Despite this, an incidental finding in the late 1980’s, paved the way for the current paradigm in obesity management, yet it was to take many more years before researchers fully appreciated the implications of what they discovered.
In 1998, it was already known that glucagon-like peptide 1 (GLP-1), a hormone that caused the release of insulin from the pancreas and suppressed glucagon release, also produced an anti-diabetic effect through lowering blood sugar. But when researchers gave an intravenous infusion of GLP-1 to healthy young men, it not only lowered blood glucose but enhanced satiety and fullness, reducing energy intake by up to 12% compared to saline.
At the time, researchers failed to understand the importance of these results and it took more than 20 years to understand the weight-lowering effect of GLP-1 agonists. The importance of this effect came to prominence in a 2017 study of the GLP-1 agonist, semaglutide, in those with type 2 diabetes. The drug led to weight losses of up to five kilograms, prompting a further study – this time in overweight and obese patients without diabetes.
The results showed that a weekly injection of semaglutide to people with a BMI greater than 30 led to a mean reduction in body weight of -14.9% compared to only -2.4% with placebo. As an added bonus, the drug also improved cardiometabolic risk factors.
But GLP-1 was not the only hormonal target in obesity. Glucose-dependent insulinotropic polypeptide (GIP) is a gut hormone responsible for increasing insulin secretion after the intake of oral glucose. The drug tirzepatide, for example, which is a dual GLP-1-GIP agonist, is able to reduce body weight by more than 20 per cent.
Another somewhat counter-intuitive target is the glucagon receptor. Under normal circumstances, stimulation of this receptor increases the release of glucose, but work in 2009 demonstrated how a glucagon-GLP-1 co-agonist, reduced body weight among diet-induced obese mice. Scientists are now taking this innovation a step further with triple receptor agonist drugs, most recently, LY3437943, which has been shown to decrease body weight.
With anti-diabetic drugs now incorporated into obesity management guidelines, have we at last found the silver bullet to stem the rising tide of obesity? Probably not.
It’s widely acknowledged that these new anti-obesity drugs are only one part of a comprehensive approach to obesity management, alongside diet and exercise. Indeed, NICE recommended use of semaglutide alongside a reduced-calorie diet and increased physical activity as a therapeutic option for weight loss in March 2023. Furthermore, once stopped, any weight lost with these drugs is quickly regained, largely because the decline in energy expenditure favouring weight regain persists long after the period of weight loss.
Ultimately, perhaps weight loss per se should not be seen as the most relevant metric. Patients who lose weight with anti-diabetic drugs also need to adopt a healthy diet and accept increased physical activity as a life-long norm.
Although some degree of weight regain is inevitable once treatment has stopped, it is recognised that the adoption of healthy lifestyle habits reduce mortality, irrespective of body mass index.
15th March 2023
The presence of hypertension irrespective or whether or not it is controlled, in patients with obesity, increases the risk of all-cause mortality according to a large, population study by Singaporean and Australian researchers.
Hypertension is the leading cause of global cardiovascular disease and premature death with the World Health Organisation estimating that 1.28 billion adults aged between 30 and 79 have hypertension, two-thirds of whom, live in low and middle-income countries. It has also become clear that as body mass index increases, so too does the risk of hypertension. Although the prevalence of hypertension among those with obesity has been found to be above 70%, much less is known about the impact on mortality of having hypertension and whether the level of control exerts a mitigating effect.
In the current study, researchers collected data on obese patients, which was defined as adults with a body mass index (BMI) of ≥ 30.0 kg/m2. Furthermore, individuals were then stratified by their hypertensive status as either having controlled hypertension (CH) (< 140/90 mmHg) with antihypertensive use, uncontrolled hypertension (UCH) ( ≥ 140/90 mmHg) with and without antihypertensive use or normotensive. The main outcome measure was all-cause mortality.
Controlled and uncontrolled hypertension and all-cause mortality
A total of 16,386 individuals with obesity were included and of whom, just over half (53.1%) were normotensive, a quarter (24.7%) had CH with the remainder having uncontrolled disease. These individuals were then followed-up for a median of 7.3 years.
The presence of hypertension per se increased the risk of all-cause mortality (Hazard Ratio, HR = 1.28, 95% CI 1.14 – 1.44, p < 0.001). After adjustment for potential confounders, the researchers found that among obese patients with UCH, there was an increased all-cause mortality risk (HR = 1.34, 95% CI 1.13 – 1.59, p = 0.001), compared to normotensive individuals. However, there was also a significantly increased mortality risk for those with CH (HR = 1.21, 95% CI 1.10 – 1.34, p < 0.001). In fact, further adjustment of the regression model for chronic kidney disease, still gave rise to a significant risk of all-cause mortality in those with CH (HR = 1.17, p = 0.007).
The authors concluded that the excess mortality risk among obese patients, irrespective of whether their hypertension was controlled, should urge health care providers to optimise disease control and advocate weight loss to achieve better outcomes in obesity.
Citation
Kong G et al. A two-decade population-based study on the effect of hypertension in the general population with obesity in the United States. Obesity (Silver Spring) 2023
28th September 2022
Semaglutide 2.4 mg given as a weekly subcutaneous injection to patients with obesity but without type 2 diabetes in combination with diet and exercise, led to a significant reduction in their 10-year risk of developing type 2 diabetes compared to placebo according to the findings of a study by US researchers presented at the 58th European Association for the Study of Diabetes (EASD) 2022.
Obesity is a major public health challenge and several lines of evidence from both observational and clinical studies over the past 30 years have clearly demonstrated a strong link between visceral and ectopic fat and the development of a clinical syndrome characterised by atherogenic dyslipidaemia, hyper-insulinaemia/glucose intolerance, hypertension, atherosclerosis and adverse cardiac remodelling and heart failure.
Although diet and exercise are recommended as a first step to reduce obesity, some evidence shows that among obese individuals who have lost weight, multiple compensatory mechanisms encouraging weight gain, can persist for at least 12 months after weight loss.
Semaglutide is a glucagon-like peptide-1 (GLP-1) analogue that is approved as an adjunct to diet and exercise in adults with insufficiently controlled type 2 diabetes mellitus. However, the STEP 1 trial showed that semaglutide at a dose of 2.4 mg weekly in combination with a lifestyle intervention could also result in sustained, clinically relevant reductions in body weight among patients with a body mass index (BMI) > 30.
Moreover, in a further trial (STEP 4), researchers examined the effect of continuing vs withdrawing treatment with semaglutide on weight loss maintenance and showed that after a 20-week run-in period, maintaining treatment with semaglutide 2.4 mg once weekly, compared with switching to placebo resulted in continued weight loss over the following 48 weeks.
With clear evidence that semaglutide could lead to weight loss, whether this also reduced an individual’s risk of developing type 2 diabetes was unclear and was the objective of the study presented at the EASD meeting. Researchers used data from both STEP 1 and 4, to assess an individual’s 10-year risk of developing type 2 diabetes.
The team used the cardiometabolic disease staging tool which uses three unmodifiable factors (age, sex, and race) and five modifiable factors (BMI, blood pressure, glucose level, high-density lipoprotein (HDL) cholesterol, and triglycerides) to predict an individual’s percentage risk of developing the disease over the next 10 years.
Semaglutide and 10-year diabetes risk
For the STEP 1 trial, the 10-year risk scores of developing T2D after 68 weeks of treatment decreased from 18.2% to 7.1% with semaglutide 2.4 mg, and 17.8% to 15.6% with placebo (p < 0.01). In STEP 4, most of the risk score reduction with semaglutide 2.4 mg occurred during weeks 0-20, from 20.6% to 11.4% but the risk score decreased further to 7.7% with continued semaglutide 2.4 mg during weeks 20-68 but increased to 15.4% after a switch to placebo (p < 0.01).
In addition, data from STEP 4 showed that weight loss was 11% for weeks 0 – 20 and a further 9% with continued semaglutide 2.4 mg vs a 6%
regain with switch to placebo for weeks 20 – 68.
The authors concluded that treatment with semaglutide 2.4 mg reduces the 10-year risk of T2D by
~60% adding that sustained treatment was required to maintain this benefit but suggested that semaglutide 2.4 mg could help prevent type 2 diabetes in people with obesity.
Citation
Garvey TW et al. Semaglutide 2.4 mg reduces the 10-year type 2 diabetes risk in people with overweight or obesity Abstract 562. EASD 2022
11th August 2022
Early time-restricted eating (eTRE) in combination with a reduction of energy intake is more effective for weight loss in comparison to a similar reduced intake of energy but where feeding occurs over a period of 12 hours or more according to the findings of a randomised trial by US researchers.
Caloric restriction whilst maintaining adequate nutritional intake, can extend both lifespan and delay the onset of age-related disorders in monkeys, indicating that this approach would be of value to human health. Moreover, in a randomised trial in humans, a 6-month period of calorie restriction (roughly 12% over 2 years) concluded that 2 biomarkers of longevity (fasting insulin level and body temperature) are decreased by prolonged calorie restriction in humans.
An alternative strategy to calorie restriction is intermittent fasting (IF) and has become popular in recent years as a means of weight loss although the benefits of IF compared to calorie restriction are still uncertain. Evidence from a 50-week randomised trial, suggested that there was no appreciable difference in outcomes between IF and continuous calorie restriction.
But what if individuals practised a form of IF and simultaneously reduced their calorie intake? Might this approach be easier to implement and increase weight loss among obese individuals?
This was the objective of the current study in which researchers examined the value of ‘early time-restricted eating’ (between 7 am and 3 pm) in combination with a reduced energy diet. This approach was compared to one in which there was a similar reduced energy intake but where food intake was spread over a 12-hour or longer period.
Participants were equally randomised to either eTRE or the control group and which the researchers said was designed to mimic typical US median meal timing habits. In both groups, participants reduced their energy intake by 500 kcal/day below their measured resting energy expenditure, measured by indirect calorimetry. In addition, all participants received counselling from a registered dietitian and were asked to exercise for 75 to 150 minutes per week.
The co-primary outcomes were weight and fat loss, whereas secondary outcomes were fasting cardiometabolic risk factors e.g., blood pressure, fasting glucose, insulin levels.
Early time-restricted eating and weight loss
A total of 90 participants with a mean age of 43 years (80% female) and mean body mass index (BMI) or 39.6, were recruited and equally randomised to eTRE or control arms.
The eTRE group lost a mean of 6.3 kg compared to a mean of 4 kg for the control group and this mean difference of 2.3 kg was statistically significant (p = 0.002). In contrast, there was no significant difference in fat loss (mean difference = -1.4, p = 0.09). Furthermore, there were no differences in trunk or visceral fat or waist circumferences.
While eTRE did not significantly reduce systolic blood pressure, the difference in mean diastolic pressure was significant (mean difference = – 4 mmHg, p = 0.04).
The authors concluded that eTRE was more effective as a weight loss strategy in conjunction with energy restriction compared to eating over a 12-hour window.
Citation
Jamshed H et al. Effectiveness of Early Time-Restricted Eating for Weight Loss, Fat Loss, and Cardiometabolic Health in Adults With Obesity: A Randomized Clinical Trial JAMA Intern Med 2022
12th July 2022
Both overweight and obese patients who have been vaccinated against COVID-19 have a similar degree of protection against severe disease and death as those of a healthy weight according to a large, population-based cohort study by researchers from the UK and Spain.
Since the start of the COVID-19 pandemic, considerable evidence has emerged indicating how obesity is a risk factor for more severe disease. For example, in a 2020 systematic review of 24 retrospective cohort studies, the odds ratio for intensive care unit admission for obese patients was 1.21 and higher still, for invasive mechanical ventilation (OR = 2.05).
With the widespread introduction of COVID-19 vaccines, it is necessary to understand how overweight and obese patients respond to vaccination. This is especially important in light of evidence showing that despite generating a robust serological response, vaccinated obese adults are twice as likely to develop influenza and influenza-like illness compared with healthy weight adults.
Furthermore, another study found that CD4(+) and CD8(+) T cells from overweight and obese individuals expressed lower levels of CD69, CD28, CD40 ligand, and interleukin-12 receptor, compared with healthy weight and which may contribute to the increased morbidity and mortality from H1N1 influenza A virus.
Despite the concern that overweight and obese patients may not produce a satisfactory immune response to vaccination, there are limited data on the association between body mass index (BMI) and COVID-19 vaccine effectiveness and the risk of severe COVID-19 outcomes after vaccination.
Using the QResearch database, in the present study, researchers used an anonymised patient data set derived from over 1,700 general practices in England and collated demographic and clinical data. They linked this information with the NHS Digital database of positive COVID-19 tests, hospital episode statistics and death certificates.
Included patients were adults and who had a BMI measurement recorded in their medical records and which were then categorised as underweight (BMI < 18.5), healthy weight (BMI 18.5 – 24.9), overweight (BMI 25 – 29.9) and obese (BMI > 30). They examined vaccine effectiveness across the different weight categories and set the main outcomes of interest as hospitalisation and death.
Overweight and obese patients and severe COVID-19 outcomes
A total of 9,171,524 individuals with a mean age of 52 years (47% male) were included in the analysis. During the period of study there were 566,461 positive tests for COVID-19, 32,808 COVID-19-related hospital admissions and 14,389 COVID-related deaths.
Across the whole cohort, 19.2% were unvaccinated, 3.1% had at least one dose, 52.6% two doses and 25% three doses. Uptake of two or three vaccine doses was more than 80% among those deemed overweight or obese.
At least 14 days after the second vaccine dose, the likelihood (based on the odds ratio, OR) of a COVID-19-related hospitalisation (compared to those who were unvaccinated) was lowest for those who were either overweight (OR = 0.32, 95% CI 0.30 – 0.34) or obese (OR = 0.32, 95% CI 0.30 – 0.34) which was similar to those with a healthy weight (OR = 0.34).
Among those who were underweight, there was a slightly higher risk of hospitalisation (OR = 0.51, 95% CI 0.41 – 0.63). However, the odds of hospitalisation after a third vaccine dose were significantly less and similar for each of the different BMI categories.
In relation to mortality, there was a similar pattern 14 days after the second dose, e.g., underweight individuals (OR = 0.60), healthy weight (OR = 0.30) with overweight and obese individuals having the same odds ratio (OR = 0.26). Mortality was also significantly lower after the third dose though there was more uncertainty given the lower number of cases.
The authors concluded that both overweight and obese patients appear to be equally well protected against severe COVID-19 outcomes as those of a healthy weight although vaccine effectiveness appeared to be less in those classed as underweight.
Citation
Piernas C et al. Associations of BMI with COVID-19 vaccine uptake, vaccine effectiveness, and risk of severe COVID-19 outcomes after vaccination in England: a population-based cohort study Lancet Diabetes Endocrinol 2022
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