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Adiposity and High CV Risk in Type 2 Diabetes

The LEADER trial of GLP-1 RA liraglutide examined anthropometric measures of adiposity and cardiovascular risk in type 2 diabetes patients.

Baseline data collected from the LEADER trial of the glucagon-like peptide (GLP)-1 receptor agonist liraglutide indicated that overweight and obesity are highly prevalent among patients with type 2 diabetes classified as being at high risk for cardiovascular disease. In addition, the study found that these patients required much higher treatment intensity compared with lower weight counterparts.

According to the study published in Cardiovascular Diabetology, there is little trial data examining the association between anthropometric measures of adiposity and cardiovascular risk in patients with diabetes and high cardiovascular risk.

In this analysis, LEADER 5, Lluis Masmiquel, of the University Institute of Health Science Research (IUNICS-IdISPa), Universitat de les Illes Balears, Palma, Majorca, Spain, and colleagues evaluated baseline data taken from the LEADER trial, which was designed to evaluate cardiovascular safety of liraglutide in patients with type 2 diabetes aged 50 years or older.

The analysis was designed to evaluate the prevalence of obesity in this patient group, any interactions between cardiovascular risk and body weight measured by waist circumference and body mass index (BMI), and how cardiovascular risk factors were treated in relation to body weight.

The analysis included data from 9340 patients with a mean BMI of 32.5 kg/m2. At baseline, only 9.1% of the patients had a BMI of less than 25. Women had a higher BMI than men (33.6 vs. 31.9), but a lower waist circumference (107.6 cm vs. 111.2 cm).

Overall the researchers found that obesity was associated with younger age, being female, and a previous smoking history. There was a significant decrease in the duration of diabetes with increasing BMI (P=0.0001) and waist circumference categories (P=0.0044).

“Recently, an inverse correlation between BMI strata, diabetes duration, and age has also been reported in a pooled analysis of cross-sectional data from Spanish patients with a mean age of 63.2 years,” the researchers wrote. “This inverse relationship could suggest less advanced disease and/or the absence of comorbidities in patients with a higher BMI, which could be related to a higher survival probability in overweight patients with type 2 diabetes or previous cardiovascular disease in prospective studies.”

Caucasian patients were most often overweight or obese, whereas Asian patients had the highest rate of healthy waist circumference. Similarly, patients from Asia had the lowest prevalence of overweight or obesity and patients from the United States had the highest rates.

In addition, the researchers found that overweight and obesity were associated with uncontrolled blood pressure, antihypertensive agents, insulin plus antihyperglycemic treatment, higher levels of triglycerides, and lower levels of high-density lipoprotein cholesterol.

“This association was observed both across the trial population and after adjustment for potential confounding factors that are also related to obesity,” the researchers wrote. “These results are generally consistent with data from observational studies both in the general population and in high cardiovascular risk patients with type 2 diabetes.”

According to Masmiqueal and colleagues, the LEADER trial will explore the long-term effect of liraglutide added to standard care on cardiovascular risk factors and weight for up to 5 years of treatment.

Funding for the LEADER trial was provided by Novo Nordisk.

Reference: Masmiquel L, et al. LEADER 5: prevalence and cardiometabolic impact of obesity in cardiovascular high-risk patients with type 2 diabetes mellitus: baseline global data from the LEADER trial. Cardiovasc Diabetol. Epub 2016 Feb 10.