Effect of exenatide, insulin and pioglitazone on bone metabolism in patients with newly diagnosed type 2 diabetes

Preclinical studies suggested that insulin, incretin and thiazolidinediones had effect on regulation of bone metabolism. But clinical evidence is limited. We assessed the effects of these antihyperglycemic agents on bone metabolism in patients with newly diagnosed type 2 diabetes. The present study was a two-center, randomized, parallel-group clinical trial. Sixty-two newly diagnosed and drug-na < ve patients with type 2 diabetes were randomized to exenatide (EXE, n = 20), mixed protamine zinc recombinant human insulin lispro injection (25R; INS, n = 21) or pioglitazone (PIO, n = 21) group for a 24-week treatment. Glycosylated hemoglobin A1c (HbA1c), body weight, body mineral density (BMD) and fasting serum concentration of bone turnover markers including osteocalcin (OC), C-telopeptide of type I collagen (CTX) and tartrate-resistant alkaline phosphatase 5b (TRAcP5b) were assessed at baseline and week 24. Baseline characteristics were similar among groups. At week 24, HbA1c improved in all patients (EXE:-2.4 +/- A 0.3 %, INS:-2.4 +/- A 0.3 %, PIO:-2.0 +/- A 0.2 %; p > 0.05 among groups). Patients treated with exenatide lost body weight remarkably (-4.7 +/- A 0.8 kg). In spite of the amelioration of glucose control, no significant improvement of OC, CTX or TRAcP5b was observed at week 24 (EXE: OC -0.619 +/- A 0.728 ng/ml, CTX 0.147 +/- A 0.046 ng/ml, TRAcP5b 0.302 +/- A 0.149 U/L;INS: OC 0.637 +/- A 0.787 ng/ml, CTX -0.012 +/- A 0.074 ng/ml, TRAcP5b 0.124 +/- A 0.395 U/L; PIO: OC -0.150 +/- A 0.691 ng/ml, CTX 0.073 +/- A 0.094 ng/ml, TRAcP5b 0.586 +/- A 0.183 U/L; p > 0.05), as well as BMD measurement, regardless of the treatments. Twenty-four-week treatment with exenatide, insulin and pioglitazone improved glucose control in patients with newly diagnosed type 2 diabetes, but had no impact on bone turnover markers or BMD.