Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Randomized Controlled Trial
. 2018 Nov;29(11):2517-2526.
doi: 10.1007/s00198-018-4637-z. Epub 2018 Jul 19.

The effect of metformin versus placebo in combination with insulin analogues on bone mineral density and trabecular bone score in patients with type 2 diabetes mellitus: a randomized placebo-controlled trial

A K Nordklint  1   2 , T P Almdal  3 , P Vestergaard  4   5 , L Lundby-Christensen  6 , T W Boesgaard  7 , L Breum  8 , B Gade-Rasmussen  9 , S B Sneppen  10 , C Gluud  11 , B Hemmingsen  12   11 , T Jensen  13 , T Krarup  14 , S Madsbad  9   15 , E R Mathiesen  13   15 , H Perrild  14 , L Tarnow  12   16 , B Thorsteinsson  12   17 , H Vestergaard  17   18   19 , S S Lund  7   20 , P Eiken  12   17
Affiliations
Randomized Controlled Trial

The effect of metformin versus placebo in combination with insulin analogues on bone mineral density and trabecular bone score in patients with type 2 diabetes mellitus: a randomized placebo-controlled trial

A K Nordklint et al. Osteoporos Int. 2018 Nov.

Abstract

Some antihyperglycemic medications have been found to affect bone metabolism. We assessed the long-term effects of metformin compared with placebo on bone mineral density (BMD) and trabecular bone score (TBS) in patients with type 2 diabetes. Metformin had no significant effect on BMD in the spine and hip or TBS compared with a placebo.

Introduction: Patients with type 2 diabetes mellitus (T2DM) have an increased risk of fractures despite a high bone mass. Some antihyperglycemic medications have been found to affect bone metabolism. We assessed the long-term effects of metformin compared with placebo on bone mineral density (BMD) and trabecular bone score (TBS).

Methods: This was a sub-study of a multicenter, randomized, 18-month placebo-controlled, double-blinded trial with metformin vs. placebo in combination with different insulin regimens (the Copenhagen Insulin and Metformin Therapy trial) in patients with T2DM. BMD in the spine and hip and TBS in the spine were assessed by dual-energy X-ray absorptiometry at baseline and after 18 months follow-up.

Results: Four hundred seven patients were included in this sub-study. There were no between-group differences in BMD or TBS. From baseline to 18 months, TBS decreased significantly in both groups (metformin group, - 0.041 [- 0.055, - 0.027]; placebo group - 0.046 [- 0.058, - 0.034]; both p < 0.001). BMD in the spine and total hip did not change significantly from baseline to 18 months. After adjustments for gender, age, vitamin D, smoking, BMI, duration of T2DM, HbA1c, and insulin dose, the TBS between-group differences increased but remained non-significant. HbA1c was negatively associated with TBS (p = 0.009) as was longer duration of diabetes, with the femoral neck BMD (p = 0.003). Body mass index had a positive effect on the hip and femoral neck BMD (p < 0.001, p = 0.045, respectively).

Conclusions: Eighteen months of treatment with metformin had no significant effect on BMD in the spine and hip or TBS in patients with T2DM compared with a placebo. TBS decreased significantly in both groups.

Trial registration: ClinicalTrials.gov (NCT00657943).

Keywords: Bone mineral density; Insulin; Metformin; Trabecular bone score; Type 2 diabetes.

PubMed Disclaimer

References

    1. Shanbhogue VV, Mitchell DM, Rosen CJ, Bouxsein ML (2016) Type 2 diabetes and the skeleton: new insights into sweet bones. Lancet Diabetes Endocrinol 4:159–173 - DOI
    1. Walsh JS, Vilaca T (2017) Obesity, type 2 diabetes and bone in adults. Calcif Tissue Int 100:528–535 - DOI
    1. Bonnet N (2017) Bone-derived factors: a new gateway to regulate glycemia. Calcif Tissue Int 100:174–183 - DOI
    1. Jain RK, Vokes T (2017) Dual-energy X-ray absorptiometry. J Clin Densitom 20:291–303 - DOI
    1. Vestergaard P (2007) Discrepancies in bone mineral density and fracture risk in patients with type 1 and type 2 diabetes--a meta-analysis. Osteoporos Int 18:427–444 - DOI

Publication types

MeSH terms

Associated data

LinkOut - more resources