Recent obesity trials demonstrate CV, diabetes benefits with weight loss
BOSTON — Results from several recent obesity trials published in 2018 demonstrate that sustained weight loss, although difficult to maintain, can substantially reduce the risk for cardiovascular events and new-onset type 2 diabetes, according to a presenter at the Cardiometabolic Health Congress.
Speaking during a presentation on late-breaking clinical obesity trials, Robert H. Eckel, MD, professor of medicine in the divisions of endocrinology, metabolism and diabetes and cardiology at the University of Colorado Denver Anschutz Medical Campus, said as the prevalence of overweight and obesity rises, the research showing an association between a reduction in body weight and living a longer, healthier life has never been clearer.
“Body weight is regulated, and it is regulated in a very substantial way so that weight loss tends to be transient and not easily maintained,” Eckel said. “What I have done is chosen four trials that I think have take-home messages that you might consider in your practice on a day-to-day basis.”
Childhood overweight , diabetes risk
In a study published online in April in The New England Journal of Medicine, Lise G. Bjerregaard, PhD, a postdoctoral research fellow in the Center for Clinical Research and Disease Prevention, Bispebjerg and Frederiksberg Hospital in Copenhagen, Denmark, and colleagues found that boys with overweight at age 7 years that persists through adolescence and early adulthood are more likely to develop type 2 diabetes as adults vs. men without childhood overweight.
Bjerregaard and colleagues analyzed data from 62,565 Danish men with height and weight measurements at age 7 and 13 years, as well as in early adulthood (aged 17-26 years), obtained from the Danish Conscription Database. Overweight was defined according to CDC criteria by age group. Follow-up began in 1977 or at age 30 years and ended on the date of a type 2 diabetes diagnosis, death or Dec. 31, 2015.
Researchers found that men with overweight at age 7 years but with remission of overweight by age 13 years that persisted through early adulthood had a risk for developing type 2 diabetes that was similar to men who had never been overweight (HR = 0.96; 95% CI, 0.75-1.21). Men with overweight only at age 13 years or with overweight only at age 7 and 13 years, but not in early adulthood, had a risk for developing type 2 diabetes in adulthood that was lower than men who had been persistently overweight, but higher than men who had never had overweight. Men with overweight at age 13 years and in early adulthood, however, had a risk for developing type 2 diabetes that was higher than men with overweight only as young adults and similar to men with overweight at all time points.
Additionally, the researchers found that obesity in early adulthood was associated with very high risk for type 2 diabetes, irrespective of BMI at age 7 years, according to the researchers.
“This is really the take-home message: If you’re overweight at 7 years, we see an associated increase in risk [for type 2 diabetes] only if the excess weight, defined by overweight, continues into adulthood,” Eckel said. “There are broader implications of this. Childhood obesity is increasing. Childhood overweight is increasing. I think we, as parents or grandparents, really need to be concerned about overweight in young children. Overall, I think this has a message that extends beyond Danish boys.”
Increased CV mortality, shorter longevity
In a study published online in February in JAMA Cardiology, researchers found that adults with obesity had an increased risk for CV morbidity and mortality and typically had shorter longevity when compared with those with normal BMI. The study, conducted by Sadiya S. Khan, MD, MSC, assistant professor of medicine and preventive medicine at Northwestern University School of Medicine, and colleagues, also found that those with overweight also had an increased risk for developing CVD at a younger age.
Researchers analyzed data from 190,672 patients (74% women; mean age for men, 46 years; mean age for women, 59 years) from 10 prospective cohort studies who were free from clinical CVD at baseline. Patients from these studies had at least one examination that included weight and height measurements, at least 10 years of follow-up and surveillance and adjudication for all subtypes of CV events and non-CV death.
The information was used to calculate lifetime and cumulative risk for CVD events and non-CVD death. Patients were categorized by sex, age and BMI. Data included 3.2 million person-years of follow-up conducted until 2015.
Both men and women who were middle-aged (aged 40-59 years) and were overweight or obese had an increased lifetime risk for incident CVD events and CVD death vs. those with normal BMI (18.5-24.9 kg/m2). Additionally, men and women who were middle-aged and had normal BMI had the shortest average years lived with CVD vs. those with higher BMI, which resulted in a relative compression of morbidity. Younger and older men and women had similar patterns.
“Despite similar longevity when compared with normal BMI [adults], overweight and obesity were associated with increased risk of developing CVD at an earlier age, resulting in a greater proportion of life lived with CVD morbidity and in women, a reduced life span,” Eckel said. “There is no obesity paradox here.”
CV safety with lorcaserin
In August, researchers presented findings from the CAMELLIA-TIMI 61 study at the European Society of Cardiology Congress that demonstrated the weight-loss drug lorcaserin (Belviq, Eisai) facilitated sustained weight loss in patients with overweight or obesity without a higher rate of major adverse cardiac events vs. similar patients assigned to placebo.
“But ultimately, a paper in The Lancet just a couple of weeks ago showed the benefit of lorcaserin in preventing or slower type 2 diabetes in patients who were overweight or obese,” Eckel said. “This shows that lorcaserin ... ultimately causes a benefit with respect to new-onset type 2 diabetes.”
IN CAMELLIA-TIMI 61, a randomized, double-blind, placebo-controlled trial, Erin Bohula, MD, DPhil, associate physician at Brigham and Women’s Hospital and instructor at Harvard Medical School, and colleagues analyzed data from more than 12,000 patients in eight countries with atherosclerotic CVD or multiple CV risk factors. At the median follow-up of 3.3 years, the primary safety outcome of major adverse CV events — a composite of CV death, myocardial infarction or stroke — occurred in 6.1% of the lorcaserin group vs. 6.2% of the placebo group (HR = 0.99; 95% CI, 0.85-1.14; P for noninferiority < .001). The annualized rate of major adverse CV events was 2% for the lorcaserin group vs. 2.1% for the placebo group, according to data presented here.
The annualized rate of extended major CV events was 4.1% for the lorcaserin group vs. 4.2% for the placebo group. Researchers also found no increased risk for new or worsening valvulopathy in patients assigned lorcaserin compared with placebo, which has been a concern with other weight-loss drugs.
“If you lost this same amount of weight with lifestyle intervention or with another agent, would this benefit still be there?” Eckel said. “There is nothing magical here about lorcaserin. It is the weight reduction that relates to improved glucose tolerance.”
Bariatric surgery, macrovascular risk
Adults with obesity and type 2 diabetes who underwent bariatric surgery were half as likely to experience macrovascular complications over 4 years, including acute MI or stroke, compared with similar patients receiving usual care, according to a retrospective analysis of more than 20,000 patients recently published in JAMA.
“Keep in mind upfront that these are observational data; this is not randomized data,” Eckel said. Still, he noted, although not a randomized clinical trial, the results “mandate our attention” to shared decision-making about bariatric surgery as an option for these patients.
In the study, David P. Fisher, MD, of the Permanente Medical Group in Northern California, and colleagues analyzed data from 5,301 adults with severe obesity (BMI 35 kg/m²) who underwent bariatric surgery between 2005 and 2011. Researchers matched those adults by age (mean, 50 years), sex, BMI, HbA1c, insulin use, observed diabetes duration and prior health care utilization with 14,934 controls receiving usual care. Researchers followed the cohort through September 2015.
The researchers found that bariatric surgery was associated with a lower composite incidence of macrovascular events at 5 years (2.1% vs. 4.3%), for an HR of 0.6 (95% CI, 0.42-0.86). Additionally, bariatric surgery was associated with lower incidence of coronary artery disease (HR = 0.64; 95% CI, 0.42-0.99). The between-group difference in cerebrovascular events, however, did not rise to significance (0.7% vs. 1.7%), according to the researchers.
Eckel called the data “impressive.”
“We are going to get outcomes that are increasingly favoring major weight reduction and an impact on cardiometabolic health, as the title of this paper represents,” he said. – by Regina Schaffer
Eckel R. Late-breaking clinical trials. Presented at: Cardiometabolic Health Congress; Oct. 24-27, 2018; Boston.
Bohula EA, et al. N Engl J Med. 2018;doi:10.1056/NEJMoa1808721.
Disclosure: Eckel is a co-chair of CMHC 2018.