Study finds that patients with type 2 diabetes treated with GLP-1RAs who reduced their BMI also lowered their cardiovascular risk.
A research team from the Cleveland Clinic has recently conducted the first study evaluating the separate real-world effects of weight loss and blood sugar control on clinical outcomes in individuals with type 2 diabetes who are being treated with antidiabetic medications, specifically GLP-1RAs, which includes drugs like Ozempic and Wegovy.
The study discovered that for every 1% decrease in BMI, there was a 4% decrease in cardiovascular risk, irrespective of changes in blood sugar levels. Additionally, effective control of blood sugar, regardless of weight change, was associated with a reduced risk of chronic kidney disease. These findings are significant from a clinical standpoint and underscore the importance of addressing both glycemic control and obesity in individuals with type 2 diabetes.
The retrospective findings, which were published in Diabetes, Obesity, and Metabolism, used de-identified electronic health record-derived data from over 1,300 patients with type 2 diabetes who were evaluated at Cleveland Clinic.
New research being presented at the annual meeting of the European Association for the Study of Diabetes (EASD) in Madrid, Spain (9-13 September) suggests that weight loss interventions could reduce the risk of severe cases of flu and other infections in people with diabetes.
The study by Rhian Hopkins and Ethan de Villiers at the University of Exeter Medical School in Exeter, UK, found evidence suggesting that a higher BMI is associated with severe infections.
In contrast, there was no evidence that mild hyperglycemia contributes to the likelihood of a severe infection.
Hopkins stated, “Up to one in three hospitalizations among people with diabetes are due to infections, and individuals with diabetes are twice as likely to be hospitalized with infections compared to the general population. They also face a high risk of readmission.”
Previous studies have found that higher BMI and poor blood sugar control are associated with severe infections. However, these studies have been observational and thus haven’t been able to prove causal links.
“If one or both of these factors can be shown to be causal, it may be possible to design interventions to lower the risk of severe infections in those at high risk, such as people with diabetes.”
The recent study utilized data from the UK Biobank, which contains medical and genetic information on approximately 500,000 individuals in the UK. The study aimed to investigate the impact of elevated BMI and inadequate blood sugar regulation on the likelihood of being hospitalized due to bacterial and viral infections.
A higher BMI was found to be associated with hospitalisation with infections. Similarly, every five-point increase in BMI was associated with a 32% increase in the likelihood a severe viral infection.
An association between mild hyperglycemia and severe infections was found. The likelihood of hospitalization due to bacterial infection increased by 32% per 10mmol/mol rise in HbA1c, a measure of blood sugar levels.
This suggested that a higher BMI is one of the causes of severe bacterial and viral infections.
However, mild hyperglycaemia did not appear to cause severe infections.
Although the study didn’t focus on individuals with diabetes, Ms Hopkins says that, given their vulnerability to infections, the results may be particularly relevant to them.
She adds: “Infections are a significant cause of death and ill health, particularly in people with diabetes. Anyone admitted to hospital with a severe infection is also at high risk of being admitted again with another. However, we currently have few practical ways to prevent this.
“This study demonstrates that higher BMI is a cause of hospital admission with infection. Clinicians could discuss weight loss options for people with a high BMI at risk of severe infections and readmission to hospital for infection.”
“While this message may be particularly relevant to people with diabetes, it applies more widely.”
Further research is needed to determine if more severe hyperglycaemia is a cause of severe infections.
“Reducing this fat may help reduce chronic pain, especially if it is present in multiple body sites.”
Reducing excess fat deposits in the abdomen may help reduce chronic musculoskeletal pain, especially if it’s experienced at multiple body sites, suggest the researchers. Previously published research has shown that obesity is associated with musculoskeletal pain. Still, it’s not known if excess fat tissue is linked to chronic musculoskeletal pain at multiple body sites, say the researchers. To find out, they drew on data from 32,409 participants in the UK Biobank study who completed questionnaires and underwent health assessments. Around half (51%) were women, and their average age was 55.
They underwent MRI scans of their abdomen to measure the amount of fat around the abdominal organs (visceral adipose tissue or VAT) and the amount of fat just under the skin that can be pinched (subcutaneous adipose tissue or SAT). When attending for their scan, participants were asked if they had experienced any pain in their neck/shoulder, back, hip, knee or ’all over the body’ for more than 3 months. The MRI scan and pain assessments were repeated around 2 years later for 638 participants. Comprehensive analyses showed a dose-response association between the number of chronic pain sites and VAT, SAT, the ratio of the two, and weight (BMI). The association was stronger in women, among whom the odds ratio of a higher number of chronic pain sites was twice as high for VAT and 60% greater for both SAT and the VAT: SAT ratio. In men, these odds ratios were 34% 39%, and 13% higher, respectively.
Higher levels of fat tissue were also associated with greater odds of reporting chronic pain, and again the association was more pronounced in women. All these associations remained even after adjusting for age, height, ethnicity, household income, educational attainment, alcohol intake, smoking status, physical activity, coexisting conditions, sleep duration, psychological problems and length of follow-up.
This is an observational study, and as such, can’t establish cause and effect, and the authors also acknowledge various limitations. These include the relatively small size of the repeat imaging sample and the absence of an assessment of severity in the pain questionnaire. They add that more follow-up visits would also have allowed more information to be gathered on patterns and fluctuations in the number of chronic pain sites. However, they conclude: “Abdominal adipose tissue was associated with chronic musculoskeletal pain, suggesting that excessive and ectopic fat depositions may be involved in the pathogenesis of multisite and widespread chronic musculoskeletal pain. Therefore, reducing abdominal adiposity may be considered a target for chronic pain management, particularly in those with pain in multiple sites and widespread pain.” They suggest that the stronger associations seen in women may be a consequence of sex differences in fat distribution and hormones.
“Amycretin mimics the action of two peptide hormones in one single molecule.”
Amycretin functions as both an amylin and glucagon-like peptide-1 (GLP-1) receptor agonist. Both of these hormones play a key role in regulating appetite and the feeling of hunger and have been shown to contribute to weight loss.
GLP-1 based treatment options are currently administered via injections. Amylin-based treatments undergoing clinical development also use this delivery method. There are no tablet-form treatment options targeting both of these biologies.
In a single-centre, placebo-controlled, double-blinded phase 1 study, adult participants with a BMI of 25.0-39.9 kg/m2 without diabetes were randomized to receive amycretin or a placebo once a day for up to 12 weeks.
The research, conducted by Novo Nordisk A/S and a clinical research unit in the US, consisted of two parts: single- and multiple-ascending dose studies. In the single-ascending dose part, doses of amycretin were tested orally, starting at 1 mg per day and increasing to 25 mg. The 10-day multiple-ascending doses study investigated doses ranging from 3 to 12 mg, while the 12-week multiple-ascending doses study involved step-wise dose escalation, starting at 3 mg and reaching a final dose of 2×50 mg.
In the first-in-human trial, amycretin appeared to have a safe and tolerable profile consistent with the drug receptor classes. Side effects were mainly mild to moderate in severity and of gastrointestinal nature, including nausea and vomiting.
Sure, the following shows the revised text: “After the trial, it was found that participants who took amycretin experienced greater weight loss compared to those who took the placebo. Those taking 50 mg of amycretin lost an average of 10.4% of their body weight after 12 weeks of treatment, while those who took the maximum tested dose of 2x50mg experienced a 13.1% reduction in body weight. In contrast, those taking the placebo only lost an average of 1.1% of their body weight during the same period.”
Notably, at the end of the treatment period, weight loss had not reached a plateau for participants taking amycretin, indicating the potential for further weight loss with extended use.
The study’s authors conclude that daily oral amylin treatment in adults with overweight or obesity and without diabetes demonstrated a safe and tolerable profile, aligning with the drug receptor classes, and resulted in significant reductions in body weight.
“A single molecule that targets both amylin and GLP-1 biology in a tablet form could provide a more convenient approach to improving outcomes for individuals with overweight or obesity.”
“However, larger and longer studies are necessary to fully evaluate the drug’s safety profile and potential.”
The risk of being diagnosed with diabetes is influenced by factors such as age, race, income level, obesity, and physical inactivity.
Type 2 diabetes increased by nearly 20% from 2012 to 2022, as per a recent study from the University of Georgia.
The researchers discovered an increase in diabetes across all sociodemographic groups. However, non-Hispanic Black individuals were particularly affected by the disease, with just under 16% of Black study participants reporting a diagnosis of Type 2 diabetes.
“More than one in five individuals aged 65 or older had the condition. In the same age group, the likelihood of being diagnosed with diabetes was more than 10 times higher than for people in the 18-to-24-year age bracket. Those between the ages of 45 and 64 were over five times more likely to receive the diagnosis.”
The research also revealed that individuals with lower incomes had a notably higher prevalence of diabetes compared to those with higher incomes. People with higher incomes had a 41% lower likelihood of being diagnosed with the disease, while individuals with a college education were 24% less likely to receive a diabetes diagnosis.
“Diabetes is on the rise in the U.S. and is projected to continue increasing in the future,” stated Sulakshan Neupane, the lead author of the study and a doctoral student in UGA’s College of Agricultural and Environmental Sciences. “The annual cost of diabetes is approximately $412 billion, encompassing medical expenses and indirect costs such as loss of productivity. This substantial amount is expected to grow as more individuals are diagnosed with the disease.”
South, Midwest particularly vulnerable to diabetes
The researchers utilized data from the nationally representative Behavioral Risk Factor Surveillance System, an ongoing health survey of over 400,000 individuals.
They used the same dataset for a paper that was published by the American Journal of Preventive Medicine in April. The paper highlighted the economic impact of Type 2 diabetes and the increased prevalence of the condition over the same study period as the current paper.
The researchers found regional differences in diabetes prevalence, with the South and Midwest experiencing large increases in Type 2 diabetes cases. Arkansas, Kentucky, and Nebraska reported the highest increases between 2012 and 2022. Over the decade-long study period, ten states saw increases of 25% or more: Arkansas, Kentucky, Nebraska, Texas, Alabama, Minnesota, Illinois, West Virginia, Delaware, and Massachusetts. “In these areas, people are at a 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
Obese and overweight individuals had a higher likelihood of being diagnosed with Type 2 diabetes. In 2022, 1 in 5 obese individuals reported having the disease, while 1 in 10 overweight participants reported the condition.
Physically active individuals had a prevalence of under 10% for diabetes, while inactive people experienced a rate closer to 19%.
“It is crucial to identify these risk factors and take steps to mitigate them,” Neupane emphasized. “Being more physically active and paying greater attention to your physical health is essential. While certain risk factors such as age and race are beyond our control, some measures can be taken to reduce the risk of diabetes, such as adopting a healthy diet, maintaining an active lifestyle, and managing weight.”
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