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Liraglutide-induced Body Composition Changes and Plasma Cardiac Natriuretic Peptides

Weight loss accompanying liraglutide therapy may be related to increased levels of natriuretic peptides…. 

Treatment with liraglutide has been shown to improve glycemic control with the added benefit of weight loss. Many believe liraglutide-induced weight loss may be associated with increased plasma natriuretic peptide concentrations. In animal models, natriuretic peptides have been associated with lipolysis, weight loss and adipocyte browning.

In a recent, prospective, 12-week observational study, researchers hypothesized that liraglutide-induced weight loss was associated with increased plasma natriuretic peptide concentrations. Patients included in this study were obese, type 2 diabetics having a glycosylated hemoglobin A1c (HbA1c) ranging from 7 to 10, and being stable on a maximal dose of metformin, or combined with either insulin, or any other oral anti-diabetes drugs – except for thiazolidinediones– for at least 3 months. Individuals with cardiac conditions, renal impairment, liver damage and recent use of any drugs which could affect weight, were excluded from the study. The average age, HbA1c and BMI were 48.5 years, 8.2% and 31.7, respectively. All patients were treated with the maximal tolerated dose of metformin before recruitment and they remained on the same mean dose throughout the study. A total of 31 of these patients received a subcutaneous injection of liraglutide for 12 weeks.

Using dual-energy X-ray absorptiometry and computerized tomography, researchers evaluated body composition, abdominal visceral adipose tissue areas and subcutaneous adipose tissue areas, pre- and post-treatment. Concentrations of plasma atrial natriuretic peptides (ANP) and B-type ventricular natriuretic peptides (BNP) were quantitatively assessed.

In all study participants, body weight, waist circumference and BMI were significantly decreased from baseline following treatment with liraglutide – with the mean reduction in body weight, waist circumference and BMI being 5.03 kg, 3.00 cm and 1.74, respectively. 61.3% of study participants lost more than 5% of their body weight. The relative total body fat mass was reduced by 2.3% from baseline while the relative total body lean mass was increased by 2.3%. Triglycerides and total cholesterol levels were significantly decreased and HDL-C level was increased. The mean changes in triglycerides levels was -1.22 mmol/L (t = -3.926, P = 0.001), total cholesterol was -0.75 mmol/L (t = -2.983, P = 0.007) and HDL-C was 0.10 mmol/L (t = 3.075, P = 0.006). No significant changes in LDL-C were observed (t = -0.668, P= 0.511). Furthermore, significant reductions in both the systolic and diastolic blood pressure were observed, with the average change of -5.3 mmHg (t = -4.008, P<0.001) and -2.5 mmHg (t = -3.053, P = 0.005), respectively.

In all study participants, plasma ANP and BNP levels significantly increased following the 12-week liraglutide treatment. ANP levels increased from a baseline 11.16 to 16.91 ng/mL and BNP from a baseline of 25.64 to 33.29 ng/mL. Researchers then stratified study participants into subgroups based on their amount of weight loss. ANP levels were significantly increased in study participants who lost more than 5% of their body weight compared to those who lost less than 5% (7.50 ng/mL  vs. 2.96 ng/mL; P<0.001).

The average increment of BNP in those who lost more than 5% of their body weight was also significantly greater than those who lost less than 5% of their body weight (10.09ng/mL vs. 2.61ng/mL, p<0.001).

Weaknesses of this study include a relatively small sample size and an observational design without controls.

Practice Pearls:
  • In addition to lowering blood glucose levels, liraglutide has multiple, favorable benefits on lipids, visceral fat and subcutaneous adipose tissue
  • Significant associations were found between increases in both plasma ANP and BNP levels and changes in body weight, indicating increases in plasma NPs may play a role in explaining how liraglutide induces sustained weight loss
  • Larger controlled studies are required to confirm findings of this study

Li CJ, Yu Q, Yu P, et al. Changes in liraglutide-induced body composition are related to modifications in plasma cardiac natriuretic peptides levels in obese type 2 diabetic patients. Cardiovasc Diabetol. 2014;13(1):36.