Spotlight on metals and medications
One study found that patients taking metformin had lower levels of copper and iron and higher levels of zinc, while another showed that use of sodium-glucose cotransporter-2 inhibitors was associated with lower rates of iron deficiency anemia than dipeptidyl peptidase-4 inhibitors.
Two recent studies looked at the association between diabetes medications and levels of various metals in the blood.
The first study, published by BMJ Open Diabetes Research & Care on Aug. 31, assessed serum levels of copper and other metals in Japanese patients with type 2 diabetes by whether they had taken metformin for at least six months (n=93) or not at all (n=96). Those who took metformin had significantly lower serum levels of copper (16.0 vs. 17.8 μmol/L; P<0.001) and iron (16.3 vs. 17.3 μmol/L; P=0.02) but higher levels of zinc (13.3 vs. 12.5 μmol/L; P=0.01). Metformin users also had higher homocysteine levels (12.2 vs. 11.2 μmol/L; P=0.03) and lower vitamin B12 levels (338.7 vs. 412.8 pmol/L; P<0.001).
The study is the first, to the authors' knowledge, to report lower copper levels in patients taking metformin. They noted that while lower levels of vitamin B12 are a latent adverse effect of metformin, the same might not be true for the metals. “These changes in metal dynamics may be related to the pharmacological effects,” the study authors wrote, adding that “the reduced copper levels of metformin users uncovered in the present study may be linked to the glucose-lowering and complication-preventive effects of the drug.” They called for more research along these lines and said that the current findings “provide novel and important perspectives on the mechanisms of action of metformin, a widely used antidiabetic drug whose effects remain incompletely understood, and might eventually contribute to future therapeutic choices.”
The second study, published by Diabetes, Obesity and Metabolism on Aug. 22, compared rates of iron deficiency anemia in adult patients in Germany who had type 2 diabetes and were taking either a sodium-glucose cotransporter-2 (SGLT-2) inhibitor or a dipeptidyl peptidase-4 (DPP-4) inhibitor in addition to metformin. A total of 28,441 of each were propensity-score matched, and over five years, the SGLT-2 group had a significantly lower cumulative incidence of iron deficiency anemia (6.9% vs. 11.3%, hazard ratio; 0.67 [95% CI, 0.58 to 0.78]). However, subgroup analyses showed that the difference was only found in patients who had taken metformin for less than three years and that it was most significant in men and those over age 60 years.
“These data underscore the potential benefits of SGLT2 inhibitors beyond glycaemic control, suggesting a favourable effect on iron homeostasis, especially in selected patient subgroups,” said the study authors. They said that the lack of effect in long-term metformin users might be due to diagnostic misclassification or overlapping causes of anemia. The study authors also noted that iron deficiency anemia is common among older patients, has risen significantly among those with diabetes in recent years, and is associated with various adverse outcomes. “Further studies are warranted to validate these findings and explore whether this hematologic benefit translates into improved clinical outcomes,” they concluded.