Rapid Changes in Serum Testosterone in Men With Newly Diagnosed Type 2 Diabetes With Intensive Insulin and Metformin

Abstract

Objective: To investigate the effect of metformin on testosterone levels in men with type 2 diabetes mellitus (T2DM).

Research design and methods: Seventy men with newly diagnosed drug-naive T2DM and HbA1c >9.0% (75 mmol/mol) were treated with intensive insulin pump therapy for 5 days to achieve glucose normalization. They were randomized to control (continued on intensive insulin only) and metformin (plus metformin) groups (1:1) for 1 month. Testosterone was measured at baseline, randomization, and after 1-month treatment.

Results: Total, free, and bioavailable testosterone increased significantly within 5 days (all P < 0.001). After 1 month, compared with the control group, the metformin group had lower total (12.7 vs. 15.3 nmol/L), free (0.20 vs. 0.24 nmol/L), and bioavailable (4.56 vs. 5.31 nmol/L) testosterone (all P < 0.05).

Conclusions: In men with T2DM, 1-month oral metformin may decrease serum testosterone levels independent of blood glucose control. The effects of long-term metformin on testosterone in men need further study.

Trial registration: ClinicalTrials.gov NCT03982238.

© 2021 by the American Diabetes Association.

Figures

Figure 1

A–C: TT, FT, and Bio-T levels at baseline (preinsulin therapy), randomization when blood glucose normalized after 5 days of intensive insulin, and the end point after 1-month therapy with intensive insulin with or without metformin. D: Baseline testosterone concentrations calculated individually and expressed as 100%, with the percentage change of TT at randomization and after 1 month of treatment with or without metformin. Data are mean ± SE. **P < 0.001, randomization vs. end point; #P < 0.05, metformin group vs. control group.