Table 1.
Effect of exenatide and placebo on biomarkers related to bone metabolism and on bone mineral density.
| Blood marker | Exenatide (n = 20) Mean ± SD [Range] | Placebo (n = 20) Mean ± SD [Range] | Time p-value | Group p-value | Time x Group p-value (No covariance) | Time x Group p-value (Prolactin covariance) |
|---|---|---|---|---|---|---|
| C-terminal cross-linking telopeptide of type I collagen (ng/L) $ | ||||||
| Baseline | 409.0 ± 229.6 [170–1160] | 475.5 ± 265.7 [30-950] | 0.93 | 0.19 | 0.15 | 0.25 |
| End of trial | 357.0 ± 171.9 [80–780] | 514.5 ± 292.5 [60–1420] | ||||
| Procollagen type I N-terminal propeptide (μg/L) | ||||||
| Baseline | 49.3 ± 23.0 [18.5–128.4] | 52.4 ± 24.9 [2.0-97.7] | 0.52 | 0.27 | 0.05 | 0.39 |
| End of trial | 46.1 ± 20.5 [17.2–104.3] | 58.7 ± 24.4 [29.2–111.9] | ||||
| Bone-specific alkaline phosphatase (μg/L) | ||||||
| Baseline | 20.9 ± 8.3 [11.3–47.1] | 22.2 ± 10.3 [8.2–50.8] | 0.65 | 0.55 | 0.61 | 0.26 |
| End of trial | 20.8 ± 7.3 [11.3–37.5] | 22.8 ± 9.7 [8.7–48.6] | ||||
| Osteocalcin (μg/L) § Baseline End of trial | 14.3 ± 7.6 [2.0–37.7] 15.4 ± 5.9 [8.0–33.5] | 16.1 ± 8.0 [6.2–39.0] 17.8 ± 8.5 [8.7–42.4] | 0.05 | 0.28 | 0.71 | 0.40 |
| Osteocalcin/CTX ratio § Baseline End of trial | 40.3 ± 21.1 [4.3–96.5] 54.1 ± 39.2 [18.7–176.7] | 51.5 ± 52.4 [19.2–256.7] 47.0 ± 40.7 [14.6–188.3] | 0.28 | 0.86 | 0.11 | 0.24 |
| Parathyroid hormone (pmol/L) $ Baseline End of trial | 4.30 ± 3.30 [1.0–14.7] 3.71 ± 1.88 [1.1–9.6]# | 4.15 ± 1.90 [1.1–10.8]# 4.08 ± 1.81 [1.5–9.3]# | 0.32 | 0.75 | 0.30 | 0.31 |
| Prolactin (mIU/L) § Baseline End of trial | 369.6 ± 397.3 [24.1–1484.0] 357.7 ± 404.0 [20.9–1416.0] | 435.3 ± 434.9 [34.2–1614.0] 372.8 ± 393.7 [30.4–1502.0] | 0.11 | 0.74 | 0.42 | – |
| Vitamin D (nmol/L) Baseline End of trial | 62.9 ± 33.8 [8.0–126.0] 69.0 ± 37.7 [16.2–135.0] | 70.4 ± 33.6 [14.2–130.0] 72.8 ± 31.3 [17.0–136.0] | 0.14 | 0.59 | 0.51 | 0.67 |
| Dual-energy X-ray absorptiometry—Bone mineral density (g/cm2) | Exenatide (n = 20) Mean ± SD [Range] | Placebo (n = 19) Mean ± SD [Range] | Time p-value | Group p-value | Time x Group p-value (No covariance) | Time x Group p-value (Prolactin covariance) |
| L2–L4 Baseline End of trial | 1.23 ± 0.19 [0.90–1.68] 1.24 ± 0.19 [0.93–1.67] | 1.13 ± 0.16 [0.92–1.49] 1.12 ± 0.16 [0.88–1.48] | 0.576 | 0.055 | 0.016* | 0.057 |
| Femoral neck Baseline End of trial | 1.05 ± 0.13 [0.82–1.28] 1.04 ± 0.13 [0.76–1.26] | 1.00 ± 0.10 [0.80–1.21] 1.00 ± 0.10 [0.82–1.16] | 0.125 | 0.223 | 0.576 | 0.720 |
| Total femur Baseline End of trial | 1.12 ± 0.12 [0.90–1.38] 1.13 ± 0.11 [0.89–1.40] | 1.08 ± 0.11 [0.90–1.35] 1.08 ± 0.11 [0.90–1.35] | 0.976 | 0.212 | 0.419 | 0.070 |
Bone mineral density was measured with dual-energy X-ray absorptiometry scanning. All outcomes were initially analyzed without covariates by two-way repeated measures ANOVA, where the between-subject factor, i.e. exenatide vs placebo, was denoted “Group,” and the within-subject factor between time points was denoted “Time.” A significant “Time × Group interaction” would indicate a difference in response between the two treatment groups. Results from ANOVA/ANCOVA are corrected for age and sex. P-values are rounded to two decimals and significant p-values are shown with an asterisk (*). The table is based on data from patients, who completed the trial.
# One observation missing. $ Square root-transformed to obtain normal distribution. § Natural logarithm-transformed to obtain normal distribution. Alkaline phosphatase and parathyroid hormone (PTH) were measured on the Vitros 5.1FS or the Vitros 5600 chemistry analyzer (Ortho Clinical Diagnostics, Raritan, NJ, USA) and total 25-hydroxycholecalciferol (vitamin D) was measured on the Cobas e411 analyzer (Roche Diagnostics, Rotkreuz, Switzerland). All three assays are electro-chemiluminescence binding assays. Prolactin was measured using an immunofluorimetric assay on the BRAHMS Kryptor Compact Plus analyzer (Thermo Scientific, Hennigsdorf, Germany). Plasma PINP, plasma CTX, plasma osteocalcin, and serum bone-specific alkaline phosphatase were measured with chemiluminescence immunoassays using the automated analyzer, iSYS (Immunodiagnostic Systems plc, Tyne and Wear, UK) according to the manufacturer's instructions.