LEADER 2: baseline calcitonin in 9340 people with type 2 diabetes enrolled in the Liraglutide Effect and Action in Diabetes: Evaluation of cardiovascular outcome Results (LEADER) trial: preliminary observations

Abstract

Aims: To report preliminary data on baseline serum calcitonin concentrations and associated clinical characteristics in a global population with type 2 diabetes before liraglutide or placebo randomization.

Methods: The ongoing LEADER trial has enrolled 9340 people with type 2 diabetes and at high risk of cardiovascular disease at 410 centres worldwide. People with baseline serum calcitonin ≤ 50 ng/l were randomized to liraglutide once daily or placebo and will be followed for up to 5 years. Serum calcitonin was measured at baseline and will be measured annually thereafter. An independent committee of thyroid experts will oversee calcitonin monitoring throughout the trial and will review all calcitonin concentrations ≥ 20 ng/l.

Results: The mean age of participants was 64.3 ± 7.2 years, 64.3% were men, and mean the body mass index was 32.5 ± 6.3 kg/m(2). The median (interquartile range) baseline serum calcitonin values were 3.9 (1.0 to >7.6) ng/l in men and 1.0 (1.0 to >1) ng/l in women. Serum calcitonin was >10 ng/l in 14.6% of men and in 0.96% of women. In sex-specific multivariable linear analysis of covariance models, a reduced glomerular filtration rate (GFR) was associated with higher serum calcitonin concentrations that were statistically significant. A 20 ml/min/1.73 m(2) decrease in estimated GFR (eGFR) was associated with a 14% increase in serum calcitonin in women and an 11% increase in men.

Conclusions: In the LEADER population, the prevalence of elevated serum calcitonin concentrations at baseline was high, and there was an inverse association between eGFR and serum calcitonin concentrations.

Keywords: c-cell disease; calcitonin; diabetes; incretins.

Figure 1

Distribution of calcitonin measurements by sex. The lower limit of quantification (LLQ) for both men and women was 2.0 ng/l. The upper limit of normal was 5.0 ng/l for women and 8.4 ng/l for men.

Figure 2

Forest plots showing the results of multivariate log-linear analysis of calcitonin concentrations in (A) men and (B) women. For each explanatory variable, the relative effect (1 is the neutral value) is depicted together with the corresponding 95% confidence interval. The right panel cites the numbers together with the p value derived from the test of ‘no difference’. HbA1c, glycated haemoglobin; eGFR, estimated glomerular filtration rate; CVD, cardiovascular disease.