A new study from King’s College London published in Nature Medicine reveals a new relationship between lipids and diseases impacting  metabolism in children, which could serve as an early warning system for conditions like liver disease.

Using machines that test blood plasma in babies that already exist in hospitals, the researchers suggest this could help doctors spot early signs of disease in children quicker and help them access the right treatment.

The findings also contest the common idea that cholesterol is a leading cause of complications around obesity in children, identifying new lipid molecules which contribute to health risks like blood pressure but are not only correlated with a child’s weight.

Lipids have traditionally been thought to be fatty acids in the body, either good or bad types of cholesterol or triglycerides, fats found in the bloodstream that is the most common in the human body. Recent studies from the same group of scientists have suggested that the picture is more complex.

Using a technique associated with chemistry called mass spectrometry, current evidence puts the types of different lipid present in the body in the thousands, each with separate functions.

Taking a control sample of 1,300 children with obesity, the team assessed their lipids in blood. Afterwards 200 of them were put on the HOLBAEK-model for a year, a lifestyle intervention for people with obesity popular in Denmark.

Subsequent readings showed that amongst the intervention group, counts of lipids tied to diabetes risk, insulin resistance and blood pressure decreased, despite limited improvements in some children’s BMI.

Dr Cristina Legido-Quigley, a group leader in Systems Medicine at King’s College London, Head of Systems Medicine at the Steno Diabetes Centre Copenhagen (SDCC) and principal author, said: “For decades, scientists have relied on a classification system for lipids that have split them into good and bad cholesterol, but now with a simple blood test we can assess a much broader range of lipid molecules that could serve as vital early warning signs for illness. In the future, this has the potential to be an entirely new way to evaluate someone’s personal risk of disease and by studying how to change lipid molecules in the body, we could even prevent metabolic diseases like diabetes altogether.”

Obesity continues to be a risk factor for conditions like fatty liver disease, but the team hope that doctors can use these measurements to treat children when they are at risk and not just a little larger than their peers.

Dr Karolina Sulek, who was part of the study and performed analysis at the SDCC, said: “Early recognition of children at risk for these life-threatening diseases is crucial. The study provides strong evidence of the great need for obesity management and gives parents confidence to intervene in their children’s life more compassionately, helping them to lose weight.”

The next step for the researchers is to help understand how genetics affects lipids and what this means for metabolic diseases, as well as how these lipids can be changed to improve health.

Researchers reported this finding on Sept. 13, 2024 at the annual meeting of the European Association for the Study of Diabetes (EASD).

The two drugs are FDA-approved for the treatment of type 2 diabetes and for weight loss. They are also being widely used off-label to treat overweight or obesity in patients with type 1 diabetes.

“Some of the mechanisms through which semaglutide and tirzepatide lower blood sugar in type 2 diabetes are also likely to be relevant in type 1 diabetes,” said study leader Janet Snell-Bergeon, MPH, PhD, of the University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA. “In addition, an increasing number of adults with type 1 diabetes are living with overweight or obesity.  These conditions can lead to insulin resistance, which makes it more difficult for people who have type 1 diabetes to control their blood sugar. Therefore, these drugs may be particularly beneficial for these patients,” she added.

The investigators evaluated retrospectively medical charts of 100 adults diagnosed with T1D, 50 of whom had been prescribed semaglutide and 50 of whom had been prescribed tirzepatide.  The majority of the subjects (84% of those prescribed semaglutide and 100% of those prescribed tirzepatide) were also overweight or obese.

The subjects were matched with 50 controls by age, sex, diabetes duration, body mass index (BMI) and glycated haemoglobin (HbA1c). The controls had not been prescribed a weight loss drug treatment.

The investigators gathered data generated at baseline before treatment began and up to one year later.

For those who had been drug treated and for the controls, respectively, mean age was 40 vs. 41 years, sex was 71 vs. 72 % female, diabetes duration was 26 vs. 27 years, BMI was 34kg/m2 vs. 34kg/m2 and HbA1c was 7.3% vs 7.3%.

Insulin pumps were used by 75% of those receiving the study drugs and 80% of controls.  The rest of the subjects injected insulin multiple times daily.

After 12 months, there were statistically significant larger average declines in weight in both of the drug-treated groups when compared to controls, who gained a small amount of weight.

The patients treated with tirzepatide lost more than twice as much weight as those taking semaglutide.

The subjects treated with semaglutide lost 9.1% of their body weight on average over 12 months, equating to 19.2lb (8.7kg).  Their BMI decreased by 3kg/m2, on average, over 12 months.

The subjects treated with tirzepatide lost 21.4% of their body weight, on average, over 12 months, equating to 49.4lb (22.4kg). Their BMI decreased by 7.5kg/m2, on average, after 12 months.

Reduction in HbA1c was greater in the semaglutide (-0.42%) and tirzepatide (-0.62%) treated groups than in controls (0.02%), but there was no significant comparative difference between the tirzepatide group and the semaglutide group

There was a statistically insignificant tendency toward greater change in BMI, weight, and HbA1c in the insulin pump users vs. those on multiple daily injections.

There were no reported hospitalizations from severe hypoglycemia or ketosis.

The authors concluded, “In this real-world, off-label study of use of semaglutide and tirzepatide in OW/OB [overweight/obese] adults with T1D, we observed weight loss of 21% and 9% in the tirzepatide and semaglutide users, respectively, with similar improved glucose control over up to a year of follow-up. There was a tendency towards higher changes in BMI, weight and HbA1c in the patients using an insulin pump. As off-label use of these drugs is increasing in patients with T1D, larger, prospective trials are needed to evaluate their efficacy and safety in OW/OB patients with T1D on different therapeutic regimens.”

Dr Snell-Bergeon added, “A growing number of individuals with type 1 diabetes are living with obesity, partly because the intensive insulin therapy that is required to manage blood sugar levels can cause weight gain. Semaglutide and tirzepatide can lead to significant weight loss in these patients and improve their blood sugar levels, which could reduce their risk of complications of obesity and diabetes, including heart disease and eye, nerve and kidney problems.”

“Glucagon-like peptide-1 agonist (GLP-1) drugs have transformed type 2 diabetes care, but weekly injections can be burdensome for patients. A single shot a month could make it much easier for people living with diabetes or obesity to stick to their drug regimens, improving quality of life and reducing side effects and diabetes complications,” said lead author Dr Claire Mégret from ADOCIA, Lyon, France, the biotechnology company who developed the hydrogel.

Semaglutide works by mimicking the hormone glucagon-like peptide 1 (GLP-1), and is currently authorised for the treatment of type 2 diabetes patients with insufficient glycaemic control and long-term weight management.

Clinical studies suggest that adherence to injected semaglutide is 39-67% for type 2 diabetes patients at one year [1a], and 40% for patients who take the drug for weight loss [1b]. Similarly, adherence to daily oral pill formulations is around 40% at one year [2].

Long-acting delivery formulations could increase drug efficacy and safety by maintaining steady drug levels in the body at optimal concentrations.

The new hydrogel delivery platform uses two innovative degradable polymers that are chemically bound to one another to form a gel, but allow slow, sustained release of soluble peptides over 1 to 3 months.

“A small dollop of gel, known as a ‘depot,’ of the semaglutide-laden hydrogel is injected under the skin,” explained Dr Mégret. “The challenge is to formulate the hydrogel to entrap the peptides to limit initial burst (early release) of semaglutide molecules and, at the same time, to allow smooth release and controlled dissolving of the gel over one month, without generating toxic molecules.”

Several formulations of the hydrogel were tested in vitro to investigate the drug release rate, duration of action, and semaglutide load to define the best candidate.

The researchers found that the hydrogel could be easily injected using an off-the-shelf needle. Additionally, the gel started forming within minutes of mixing, ensuring sufficient time for the injection while minimising spread at the injection site, so that the depot is small enough to be comfortable and inconspicuous.

In vitro drug release assessments for all formulations showed extended and constant release rates over 1 to 3 months. The researchers also found that the release duration could be tailored through optimisation of the hydrogel properties and loading.

The hydrogel-semaglutide formulation was also tested in six laboratory rats. In the rats, a single injection of the hydrogel-based therapy, showed limited burst (early release) and a regular release over a one-month period.

Importantly, the hydrogel was well tolerated with no inflammatory reaction over the treatment period.

“Our pre-clinical results demonstrate that the regular, slow release of semaglutide over one month after administering a single dose, with limited early release, is achievable. Next we will be testing the hydrogel platform in pigs, whose skin and endocrine systems are most similar to those in humans. If that goes well, we will move forward the platform development by expecting clinical trials within the next few years,” said Dr Mégret.

Researchers from Brigham and Women’s Hospital, Harvard Medical School, and Northwestern University examined NHANES (National Health and Nutrition Examination Survey) between 2011 and 2020 to the Medicare beneficiaries who are most likely to be newly eligible for semaglutide based on SELECT trial criteria. They also describe which beneficiaries had any increased risk for future cardiac events and could be eligible pending future evidence generation and Part D coverage decisions. The researchers then estimated the maximum cost to Medicare Part D that would arise from providing coverage to these various groups of patients by multiplying the number of newly eligible Medicare beneficiaries by the annual net price of semaglutide, generated by subtracting a 41% average discount from the manufacturer list price of the medication in March 2024. The data showed that approximately 61% of Medicare-eligible adults with complete data had obesity and would potentially benefit from semaglutide for its weight loss benefits. However, when established cardiovascular disease is defined narrowly as in the SELECT trial, only 1 in 7, or 3.6 million people, would be likely to be newly eligible for semaglutide. Alternatively, if a more liberal definition of established CVD risk were used by Part D plans, then 15.2 million people would be eligible. Even in the most likely scenario where conservative definitions of CVD are used and many people do not stay on semaglutide long-term, Medicare spending could increase by $10 billion annually. The authors note that the analysis estimates maximum budgetary impacts but is not a spending projection and does not account for future payment reforms via the Inflation Reduction Act.

Global meat production has increased rapidly in recent decades and meat consumption exceeds dietary guidelines in many countries.  Earlier research indicated that higher intakes of processed meat and unprocessed red meat are associated with an elevated risk of type 2 diabetes, but the results have been variable and not conclusive.

Poultry such as chicken, turkey, or duck is often considered to be an alternative to processed meat or unprocessed red meat, but fewer studies have examined the association between poultry consumption and type 2 diabetes.

To determine the association between consumption of processed meat, unprocessed red meat and poultry and type 2 diabetes, the team led by researchers at the University of Cambridge used the global InterConnect project to analyse data from 31 study cohorts in 20 countries. Their extensive analysis took into account factors such as age, gender, health-related behaviours, energy intake and body mass index.

The researchers found that the habitual consumption of 50 grams of processed meat a day – equivalent to 2 slices of ham – is associated with a 15% higher risk of developing type 2 diabetes in the next 10 years. The consumption of 100 grams of unprocessed red meat a day – equivalent to a small steak – was associated with a 10% higher risk of type 2 diabetes.

Habitual consumption of 100 grams of poultry a day was associated with an 8% higher risk, but when further analyses were conducted to test the findings under different scenarios the association for poultry consumption became weaker, whereas the associations with type 2 diabetes for each of processed meat and unprocessed meat persisted.

Professor Nita Forouhi of the Medical Research Council (MRC) Epidemiology Unit at the University of Cambridge, and a senior author on the paper, said:

“Our research provides the most comprehensive evidence to date of an association between eating processed meat and unprocessed red meat and a higher future risk of type 2 diabetes. It supports recommendations to limit the consumption of processed meat and unprocessed red meat to reduce type 2 diabetes cases in the population.

While our findings provide more comprehensive evidence on the association between poultry consumption and type 2 diabetes than was previously available, the link remains uncertain and needs to be investigated further.”

InterConnect uses an approach that allows researchers to analyse individual participant data from diverse studies, rather than being limited to published results. This enabled the authors to include as many as 31 studies in this analysis, 18 of which had not previously published findings on the link between meat consumption and type 2 diabetes. By including this previously unpublished study data the authors considerably expanded the evidence base and reduced the potential for bias from the exclusion of existing research.

Lead author Dr Chunxiao Li, also of the MRC Epidemiology Unit, said:

“Previous meta-analysis involved pooling together of already published results from studies on the link between meat consumption and type 2 diabetes, but our analysis examined data from individual participants in each study. This meant that we could harmonise the key data collected across studies, such as the meat intake information and the development of type 2 diabetes.

Using harmonised data also meant we could more easily account for different factors, such as lifestyle or health behaviours, that may affect the association between meat consumption and diabetes. “

Professor Nick Wareham, Director of the MRC Epidemiology Unit, and a senior author on the paper said:

“InterConnect enables us to study the risk factors for obesity and type 2 diabetes across populations in many different countries and continents around the world, helping to include populations that are under-represented in traditional meta-analyses.

Most research studies on meat and type 2 diabetes have been conducted in USA and Europe, with some in East Asia. This research included additional studies from the Middle East, Latin America and South Asia, and highlighted the need for investment in research in these regions and in Africa.

Using harmonised data and unified analytic methods across nearly 2 million participants allowed us to provide more concrete evidence of the link between consumption of different types of meat and type 2 diabetes than was previously possible.”

InterConnect was initially funded by the European Union’s Seventh Framework Programme for research, technological development and demonstration under grant agreement no 602068.

Reference

Li, C et al. Meat consumption and incident type 2 diabetes: a federated meta-analysis of 1·97 million adults with 100,000 incident cases from 31 cohorts in 20 countries. Lancet Diabetes Endocrinol.; 20 August 2024. DOI:10.1016/S2213-8587(24)00179-7

The researchers found an increase in diabetes among all sociodemographic groups. But non-Hispanic Black people were particularly hard hit by the disease, with just under 16% of Black study participants reporting being diagnosed with Type 2 diabetes.

More than one in five individuals aged 65 or older had the condition. The same age group was more than 10 times as likely to be diagnosed with diabetes than people in the 18-to-24-year age bracket. People between the ages of 45 and 64 were over five times as likely to receive the diagnosis.

The study also found that individuals with lower incomes had a significantly higher prevalence of diabetes than their higher income counterparts. People with high incomes were 41% less likely to be diagnosed with the disease. And individuals with a college education were 24% less likely to be given a diabetes diagnosis.

“Diabetes is increasing day by day in the U.S., and it will increase even more in the coming years,” said Sulakshan Neupane, lead author of the study and a doctoral student in UGA’s College of Agricultural and Environmental Sciences. “Diabetes costs around $412 billion, including medical costs and indirect costs like loss of productivity. That’s a huge amount, and it’s only going to increase as more people are diagnosed with the disease.”

South, Midwest particularly vulnerable to diabetes

The researchers used data from the nationally representative Behavioral Risk Factor Surveillance System, an ongoing health survey of more than 400,000 people.

They relied on the same dataset for a paper published by the American Journal of Preventive Medicine in April, which emphasized the economic burden of Type 2 diabetes and the increased prevalence of the condition over the same study period as the current paper.

In addition to other risk factors, the researchers found regional differences in diabetes prevalence as well.

The South and Midwest, in particular, experienced large jumps in the number of individuals with Type 2 diabetes, with Arkansas, Kentucky and Nebraska reporting the highest increases between 2012 and 2022.

Ten states saw increases of 25% or more over the decade-long study period: Arkansas, Kentucky, Nebraska, Texas, Alabama, Minnesota, Illinois, West Virginia, Delaware and Massachusetts.

“In these areas, people are at higher risk of developing diabetes, so policymakers and public health officials need to focus on these regions,” Neupane said.

Overweight, obese individuals more likely to have diabetes

Overweight and obese participants were also more likely to report being diagnosed with Type 2 diabetes. About one in five obese individuals reported having the disease in 2022 while one in 10 overweight participants reported having the condition.

Physical activity seemed to guard against diabetes to an extent, with physically active individuals facing a prevalence of under 10% while inactive people experienced a rate at closer to 19%.

“Identifying these risk factors and acting to mitigate them is key,” Neupane said. “Be more active. Pay more attention to your physical health. Some risk factors like age and race cannot be modified, but you can do something to lower risk of diabetes, like, healthy eating, maintaining an active lifestyle and losing weight.”

Published in Diabetes, Obesity and Metabolism, the study was co-authored by Wojciech Florkowski, of UGA’s Department of Agricultural and Applied Economics; Uttam Dhakal and Chandra Dhakal, of CDC Atlanta.

Vision loss in type 2 diabetes results from diabetic retinopathy, caused by damage to blood vessels in the retina, the light-sensitive layer of tissue in the back of your eye. The disease can appear without warning.

“The ability to predict which patients are most at risk could constitute a significant advance in diagnosis and management of diabetes, which has reached epidemic proportions,” said Harrison.  “Early diagnosis and detection, especially if location-specific, could aid in delaying diabetic retinopathy and over the long term, saving sight.”

Diabetes is the number one cause of vision loss in working-age Americans. Also alarming, about 44% of American adults have prediabetes and it is not currently known when and how prediabetes affects the eye. Many patients with prediabetes are unaware of their condition.

Although patients with prediabetes are known to have impaired fasting glucose, impaired glucose tolerance, and elevated hemoglobin A1c, there is still a significant gap in understanding how and when prediabetes impacts eye health.

“It is important that we close this gap as there are no treatments in the eye outside of glycemic control for early type 2 diabetes or prediabetes, and to learn which type of glucose processing changes are most related to eye disease,” said Harrison.

Harrison’s team is undertaking unique research, never done before, in that they will study both the front and the back of the eye and different types of glucose dysfunction. The team includes the laboratories of Rachel Redfern, Maria Walker and Kaitlyn Sapoznik in Optometry and Marc Hamilton in Health and Human Performance. Ted Zderic, Julia Benoit, Deborah Hamilton and Bismark Owusu-Afriyie also have key roles in the project.

To explore how glucose dysregulation affects the vascular and neural retina, cornea, and tear film, the team will investigate whether tests like fat distribution, activity levels, and oral glucose tolerance in type 2 diabetes patients are linked to or can predict ocular health.

“Our central hypothesis is that local retinal oxygenation is altered by changes in glucose tolerance. This drives the relationship between vessel changes and retinal function, in local retinal areas,” said Harrison.

After comparing the subjects, the team will follow up with them after one-and two- years to assess ocular and metabolic changes over time.

“We expect that differences in impaired glucose tolerance and phenotypes will alter ocular testing over time, especially in prediabetes,” said Harrison.

“Compared to prior studies that relied solely on epidemiological data, we integrated multiple layers of information, including epidemiological data, conventional metabolic biomarkers, and cutting-edge metabolomics,” said lead author Fenglei Wang, research associate in the Department of Nutrition. “This allowed us to achieve a more comprehensive understanding of the association between iron intake and T2D risk, as well as potential metabolic pathways underlying this association.”

The study will be published August 13 in Nature Metabolism.

The researchers assessed the link between iron and T2D using 36 years of dietary reports from 206,615 adults enrolled in the Nurses’ Health Studies I and II and the Health Professionals Follow-up Study. They examined participants’ intake of various forms of iron—total, heme, non-heme, dietary (from foods), and supplemental (from supplements)—and their T2D status, controlling for other health and lifestyle factors.

The researchers also analyzed the biological mechanisms underpinning heme iron’s relationship to T2D among smaller subsets of the participants. They looked at 37,544 participants’ plasma metabolic biomarkers, including those related to insulin levels, blood sugar, blood lipids, inflammation, and two biomarkers of iron metabolism. They then looked at 9,024 participants’ metabolomic profiles—plasma levels of small-molecule metabolites, which are substances derived from bodily processes such as breaking down food or chemicals.

The study found a significant association between higher heme iron intake and T2D risk. Participants in the highest intake group had a 26% higher risk of developing T2D than those in the lowest intake group. In addition, the researchers found that heme iron accounted for more than half of the T2D risk associated with unprocessed red meat and a moderate proportion of the risk for several T2D-related dietary patterns. In line with previous studies, the researchers found no significant associations between intakes of non-heme iron from diet or supplements and risk of T2D.

The study also found that higher heme iron intake was associated with blood metabolic biomarkers associated with T2D. A higher heme iron intake was associated with higher levels of biomarkers such as C-peptide, triglycerides, C-reactive protein, leptin, and markers of iron overload, as well as lower levels of beneficial biomarkers like HDL cholesterol and adiponectin.

The researchers also identified a dozen blood metabolites—including L-valine, L-lysine, uric acid, and several lipid metabolites—that may play a role in the link between heme iron intake and TD2 risk. These metabolites have been previously associated with risk of T2D.

On a population level, the study findings carry important implications for dietary guidelines and public health strategies to reduce rates of diabetes, according to the researchers. In particular, the findings raise concerns about the addition of heme to plant-based meat alternatives to enhance their meaty flavor and appearance. These products are gaining in popularity, but health effects warrant further investigation.

“This study underscores the importance of healthy dietary choices in diabetes prevention,” said corresponding author Frank Hu, Fredrick J. Stare Professor of Nutrition and Epidemiology. “Reducing heme iron intake, particularly from red meat, and adopting a more plant-based diet can be effective strategies in lowering diabetes risk.”

The researchers noted that the study had several limitations, including the potential for incomplete accounting for confounders and measurement errors in the epidemiological data. In addition, the findings—based on a study population that was mostly white—need to be replicated in other racial and ethnic groups.

Other Harvard Chan authors included Andrea Glenn, Anne-Julie Tessier, Danielle Haslam, Marta Guasch-Ferré, Deirdre Tobias, Heather Eliassen, JoAnn Manson, Kyu Ha Lee, Eric Rimm, Dong Wang, Qi Sun, Liming Liang, and Walter Willett.

“Integration of epidemiological and blood biomarker analysis links heme iron intake to increased type 2 diabetes risk,” Fenglei Wang, Andrea J. Glenn, Anne-Julie Tessier, Zhendong Mei, Danielle E. Haslam, Marta Guasch-Ferré, Deirdre K. Tobias, A. Heather Eliassen, JoAnn E. Manson, Clary Clish, Kyu Ha Lee, Eric B. Rimm, Dong D. Wang, Qi Sun, Liming Liang, Walter C. Willett, Frank B. Hu, Nature Metabolism, August 13, 2024, doi: 10.1038/s42255-024-01109-5

Visit the Harvard Chan School website for the latest news, press releases, and multimedia offerings.

Malnutrition during early pregnancy is known to elevate diabetes risk later in life. With 187,000 children born in Ukraine in 2023, Klimek and Thurner suggest that the current diabetes prevalence rate of 7.1% could result in an additional 13,000 to 19,000 cases of diabetes in this birth cohort alone.

Global impact

Globally, the disruption of crucial food exports due to the conflict has pushed an estimated 23 million people into hunger. Considering other supply chain interruptions and weather-related shocks, projections suggest that up to 122 million more people could suffer from hunger compared to 2019. “This could potentially lead to up to 180,000 additional Type 2 diabetes cases worldwide,” the researchers say.

They caution that while these estimates are not intended to be quantitative predictions, they do underscore the profound and often overlooked—especially indirect—effects of geopolitical events on public health.

Ukraine – a key producer

Prior to the war, Ukraine was a major global agricultural producer, ranking as the largest exporter of sunflower oil, the fourth-largest exporter of corn, and the fifth-largest exporter of wheat. The modeled impacts of Ukraine’s agricultural production loss suggest that countries like Moldova, Libya, Lebanon, and Tunisia could face significant wheat shortages, with extensive repercussions for food products that rely on wheat as an ingredient.

Why this matters

Klimek and Thurner emphasize the importance of addressing these indirect consequences of conflicts and supply chain disruptions: “Our estimates are meant to illustrate the scale of the impact on public health, so that health authorities can become aware of these emerging high-risk groups and potentially adjust screening and early prevention measures for the coming decades,” the researchers stated. They also stress the urgent need to diversify global food supply chains and reduce dependencies.

Famine and diabetes

The link between hunger and diabetes is well-documented, with studies from historical famines in the Netherlands, China, and Austria, for example, showing that malnutrition during early pregnancy can significantly increase type 2 diabetes risk later in life. Recent research into the Ukrainian famine of 1932-33 by Lumey et al. has provided new insights into this relationship at a more granular level. By analyzing monthly birth cohorts and regional variations in famine severity, they found that severe malnutrition during early pregnancy can increase diabetes risk by 1.5 to 2 times.

This heightened risk is believed to stem from metabolic changes triggered by fetal exposure to poor nutrition, which prepares the body for a nutrient-scarce environment. When this environment changes, the mismatch can result in a higher likelihood of developing diabetes.

About CSH

The Complexity Science Hub (CSH) is Europe’s research center for the study of complex systems. We derive meaning from data from a range of disciplines – economics, medicine, ecology, and the social sciences – as a basis for actionable solutions for a better world. Established in 2015, we have grown to over 70 researchers, driven by the increasing demand to gain a genuine understanding of the networks that underlie society, from healthcare to supply chains. Through our complexity science approaches linking physics, mathematics, and computational modeling with data and network science, we develop the capacity to address today’s and tomorrow’s challenges.

Prescription fills for the drug best known as Ozempic or Wegovy — semaglutide — increased by more than 400% between January 2021 and December 2023, according to research out today in  JAMA Health Forum.

Approved first for type 2 diabetes, then for weight loss, studies show that semaglutide also improves blood pressure and reduces cardiovascular disease — problems that plague millions of Americans. Yet the lion’s share of prescriptions went to people with private insurance.

“Given the proven cardiovascular benefits of Ozempic and Wegovy when used for diabetes or obesity, and the disproportionate burden of diabetes and obesity in Black/Latinx Medicaid and Part D populations, these findings suggest that their lower use in Medicaid and Part D may worsen disparities in diabetes and obesity outcomes,” said senior author Dima Qato, an associate professor at the USC Mann School of Pharmacy & Pharmaceutical Sciences and senior scholar at the USC Leonard D. Schaeffer Center for Health Policy & Economics.

“I think all the current attention in the media on semaglutide’s anti-obesity effect obscures the fact that the drug is also hugely important for treating diabetes. It’s the reason why I’ve been able to get some of my patients off insulin,” said first author Christopher Scannell, a physician and postdoctoral researcher at the Schaeffer Center. “If only certain patient populations get access to these medications — those primarily with private insurance, more generous health plans — then there’s a huge percentage of the U.S. population that isn’t getting access to these medications. And that brings up a very significant equity issue.”

Ozempic and Wegovy are once-weekly injections. Another form of semaglutide, Rybelsus, is a daily pill. Ozempic was approved in 2017, followed by Rybelsus in 2019, to treat type 2 diabetes. Wegovy, approved 2021, is a higher-dose version that’s specifically approved for weight loss. Ozempic’s sticker price is about $1,000 per month, while Wegovy is listed around $1,350.

For the study, researchers used data from IQVIA’s National Prescription Audit PayerTrak, which captures 92% of prescriptions filled and dispensed to individuals at retail pharmacies in the United States.

Then, they calculated monthly fills for semaglutide by drug brand (Ozempic, Wegovy, and Rybelsus) and by payment method (commercial insurance, Medicaid, Medicare Part D, and cash) between January 2021 and December 2023.

Prescription fills reached 2.6 million by December 2023. Ozempic persistently accounted for most of the prescriptions, but prescription fills for Wegovy, approved for weight loss in June 2021, soared by more than 1,361% between July 2021 and December 2023.  Awareness of the drugs’ weight-loss benefits shot up in late 2022 and likely contributed to shortages of Ozempic and Wegovy, first reported by the FDA in March 2022.

• Medicaid accounted for less than 10% of semaglutide fills for all three drug brands in 2023. Access via Medicaid is a state-level decision, Scannell said. Depending on the budget — and politics — of where you live, the drugs may or may not be covered. (Medicaid provides assistance to low-income people, the elderly and some people with disabilities.)
• Medicare Part D accounted for 28.5% and 32.9% of Ozempic and Rybelsus fills, respectively, in 2023; it only accounted for 1.2% of Wegovy fills. Medicare Part D doesn’t cover the drugs for obesity unless a patient also has a co-morbidity such as cardiovascular disease as well  — the very problem Wegovy or Ozempic can prevent.
• Approximately 1% or less of all semaglutide fills went to people paying cash in 2023.

In the context of treating obesity, Scannell said, “if Medicare is only covering these drugs for patients who have obesity and a co-morbidity, it may be forcing patients who only have obesity to develop these additional chronic conditions before they can get access to the medications. It’s like saying ‘You have to be sick enough, then we’ll cover that medication for you.’”

The researchers said future studies should examine how changes in Medicare Part D and Medicaid coverage restrictions influence disparities in access to these essential medications. In addition, further research could examine individual-level variables such as age, race, and ethnicity and whether the drugs were prescribed for obesity or diabetes.

In addition to Scannell and Qato, other authors include John Romley, Rebecca Myerson and Dana Goldman, all of USC.

Those who experienced loneliness were among the most impacted.

“During the pandemic, loneliness almost tripled the risk of depression in older adults with diabetes,” says clinical pharmacist and first author ZhiDi Deng. “This not only highlights the impact of quarantines and lock-downs on individuals’ mental health. It also shows us that there is room for improvement on how we can better deliver services to older adults with diabetes in future public health crises.”

Although not as severely impacted as those with a history of depression, one in eight older adults with diabetes who had no history of depression prior to the pandemic were depressed in the autumn of 2020. “The pandemic has taken a significant toll on the mental health of everyone, particularly older adults with chronic conditions such as diabetes,” says co-author Grace Li, a research assistant at the University of Toronto’s Institute for Life Course and Aging (ILCA). “It’s important for primary health providers to be vigilant for signs of depression among their older patients, even those who were doing well in the past.”

The researchers identified several other factors that were associated with a higher risk of depression among those with diabetes, such as being female, having functional limitations or chronic pain, and experiencing family conflict.

They also reported some unexpected findings. The researchers found that those who were separated, divorced, or widowed had lower odds of recurrent depression during the pandemic than those who were married or in common-law relationships. “This is different from research conducted before the pandemic that indicated married individuals usually are less depressed,” said co-author Dorina Cadar, Senior Lecturer in Neuroepidemiology and Dementia at the Centre for Dementia Studies at Brighton and Sussex Medical School and the director of the Cognitive Epidemiology, Dementia, and Ageing Research lab. “We hypothesized that participants who were married during the pandemic experienced worse mental health because the need to stay for extended periods of time in close living proximity during the lockdowns or quarantine could possibly exacerbate any relationship conflicts. Our findings indicate that those who were experiencing family conflict during the pandemic had more than triple the risk of depression during the pandemic.”

The second unexpected finding was that those with higher income prior to the pandemic had a greater risk of depression during the pandemic than those who were poorer.  In pre-pandemic research, higher income is associated with a lower prevalence of depression.

“We hypothesized that this finding may have been influenced by the generous response of the Canadian government with the Canadian Emergency Response Benefit (CERB), which may have had a protective impact on the mental health of low-income Canadians. CERB provided Canadians who lost employment during the pandemic with a $2000 monthly income. For some low-income individuals and households, this would actually increase their monthly income, thereby reducing financial-related stress among this population,” said co-author Maria Rowsell, a research assistant at the University of Toronto’s ILCA.

The study was conducted using data from the Canadian Longitudinal Study on Aging (CLSA) surveys. The CLSA is a large national longitudinal study involving older Canadians with diabetes. This study identified 2,730 individuals with diabetes in the CLSA sample. In this group, 1,757 individuals had no pre-pandemic history of depression, and 973 had a pre-pandemic history of depression. The study was published online this month in the journal Archives of Gerontology and Geriatrics Plus.

“The long-term implications of the pandemic extend far beyond physical health,” said senior author Professor Esme Fuller-Thomson of the University of Toronto’s Factor-Inwentash Faculty of Social Work and Director of the ILCA. “It is important to improve access to mental health services for people with diabetes, particularly during periods of increased stress. Interventions that have shown promising results to support the mental health of individuals with comorbid depression and diabetes include cognitive behavioural therapy and psychoeducation.  We need to improve access to these important services.”

Researchers from the Perelman School of Medicine at the University of Pennsylvania and Cedars-Sinai studied data from TriNetX, a federated health research network with records for 45 million individuals in the United States, to delineate the annual trend in new prescriptions of GLP-1RAs between 2011 and 2023, categorized by the presence of diabetes and comorbid conditions related to diabetes or obesity. New prescriptions were defined as users who received GLP-1RAs for the first time in their records in the TrinetX database. The data showed that of the 1 million new GLP-1RA users identified during the study timeframe, users were disproportionately female, non-Hispanic White, and had a BMI of 30 kg/m2 or greater. During the same period, there was a 2-fold increase in the proportions of users without type 2 diabetes but with a BMI of 30 kg/m2 or greater, or in those with a BMI of 27 to 30 kg/m2 and an obesity-related comorbid condition. Additionally, the proportion of users without FDA-approved indications increased from 0.21% in 2019 to 0.37% in 2023. In 2019, semaglutide and liraglutide constituted 31.4% and 35.3% of all new GLP-1RA prescriptions, respectively. In 2023, these proportions increased to 88.1% for semaglutide, and decreased to 10.3% for liraglutide.

Abstract: https://www.acpjournals.org/doi/10.7326/M24-0019