TY - JOUR
T1 - Effect of Metformin vs. Placebo in Combination with Insulin Analogues on Bone Markers P1NP and CTX in Patients with Type 2 Diabetes Mellitus
AU - Nordklint, Azra Karahasanovic
AU - Almdal, Thomas Peter
AU - Vestergaard, Peter
AU - Lundby-Christensen, Louise
AU - Jørgensen, Niklas Rye
AU - Boesgaard, Trine W
AU - Breum, Leif
AU - Gade-Rasmussen, Birthe
AU - Sneppen, Simone B
AU - Gluud, Christian
AU - Hemmingsen, Bianca
AU - Krarup, Thure
AU - Madsbad, Sten
AU - Mathiesen, Elisabeth R
AU - Perrild, Hans
AU - Tarnow, Lise
AU - Thorsteinsson, Birger
AU - Vestergaard, Henrik
AU - Lund, Søren S
AU - Eiken, Pia
PY - 2020/8
Y1 - 2020/8
N2 - Preclinical studies have shown a potential osteoanabolic effect of metformin but human studies of how metformin affects bone turnover are few. A post hoc sub-study analysis of an 18-month multicenter, placebo-controlled, double-blinded trial in type 2 diabetes mellitus (T2DM), randomizing participants to metformin versus placebo both in combination with different insulin analogue regimens (Metformin + Insulin vs. Placebo + Insulin). Patients were not treatment naive at baseline, 83% had received metformin, 69% had received insulin, 57.5% had received the combination of metformin and insulin before entering the study. Bone formation and resorption were assessed by measuring, N-terminal propeptide of type I procollagen (P1NP) and C-terminal telopeptide of type I collagen (CTX) at baseline and end of study. The influence of gender, age, smoking, body mass index (BMI), T2DM duration, glycosylated hemoglobin A1c (HbA1c), c-reactive protein (CRP) and insulin dosage was also included in the analyses. The levels of bone formation marker P1NP and bone resorption marker CTX increased significantly in both groups during the trial. P1NP increased less in the Metformin + Insulin compared to the placebo + insulin group (p = 0.001) (between group difference change), while the increases in CTX levels (p = 0.11) were not different. CRP was inversely associated (p = 0.012) and insulin dosage (p = 0.011) was positively related with change in P1NP levels. BMI (p = 0.002) and HbA1C (p = 0.037) were inversely associated with change in CTX levels. During 18 months of treatment with metformin or placebo, both in combination with insulin, bone turnover increased in both groups. But the pattern was different as the bone formation marker (P1NP) increased less during Metformin + Insulin treatment, while change in bone resorption (CTX) was not significantly different between the two groups.
AB - Preclinical studies have shown a potential osteoanabolic effect of metformin but human studies of how metformin affects bone turnover are few. A post hoc sub-study analysis of an 18-month multicenter, placebo-controlled, double-blinded trial in type 2 diabetes mellitus (T2DM), randomizing participants to metformin versus placebo both in combination with different insulin analogue regimens (Metformin + Insulin vs. Placebo + Insulin). Patients were not treatment naive at baseline, 83% had received metformin, 69% had received insulin, 57.5% had received the combination of metformin and insulin before entering the study. Bone formation and resorption were assessed by measuring, N-terminal propeptide of type I procollagen (P1NP) and C-terminal telopeptide of type I collagen (CTX) at baseline and end of study. The influence of gender, age, smoking, body mass index (BMI), T2DM duration, glycosylated hemoglobin A1c (HbA1c), c-reactive protein (CRP) and insulin dosage was also included in the analyses. The levels of bone formation marker P1NP and bone resorption marker CTX increased significantly in both groups during the trial. P1NP increased less in the Metformin + Insulin compared to the placebo + insulin group (p = 0.001) (between group difference change), while the increases in CTX levels (p = 0.11) were not different. CRP was inversely associated (p = 0.012) and insulin dosage (p = 0.011) was positively related with change in P1NP levels. BMI (p = 0.002) and HbA1C (p = 0.037) were inversely associated with change in CTX levels. During 18 months of treatment with metformin or placebo, both in combination with insulin, bone turnover increased in both groups. But the pattern was different as the bone formation marker (P1NP) increased less during Metformin + Insulin treatment, while change in bone resorption (CTX) was not significantly different between the two groups.
KW - Bone turnover
KW - CTX
KW - Insulin
KW - Metformin
KW - P1NP
KW - Type 2 diabetes
UR - http://www.scopus.com/inward/record.url?scp=85085366484&partnerID=8YFLogxK
U2 - 10.1007/s00223-020-00711-5
DO - 10.1007/s00223-020-00711-5
M3 - Journal article
C2 - 32468187
SN - 0171-967X
VL - 107
SP - 160
EP - 169
JO - Calcified Tissue International
JF - Calcified Tissue International
IS - 2
ER -