Influence of Therapy with Metformin on the Concentration of Certain Divalent Cations in Patients with Non-insulin-Dependent Diabetes Mellitus

Abstract

Research was performed on a group of 30 patients with non-insulin-dependent diabetes mellitus (NIDDM), who never received antidiabetic medication before, and on a group of 17 healthy adults. The patients were administered treatment with metformin, 1,000 mg/day. Plasmatic and urinary concentration of magnesium have been measured, copper and zinc along with the concentrations of glucose, HDL, LDL, cholesterol, tryglicerides, HbA1c, and total erythrocyte magnesium, in advance and after 3 months of treatment. Data showed significant differences in the NIDDM group vs the control group: for plasma magnesium-1.95 ± 0.19 vs 2.20 ± 0.18 mg/dl, p < 0.001; urine magnesium-237.28 ± 34.51 vs 126.25 ± 38.22 mg/24 h, p < 0.001; erythrocyte magnesium-5.09 ± 0.63 vs 6.38 ± 0.75 mg/dl, p < 0.001; plasma zinc-67.56 ± 6.21 vs 98.41 ± 20.47 μg/dl, p < 0.001; urine zinc-1,347.54 ± 158.24 vs 851.65 ± 209.75 μg/24 h, p < 0.001; plasma copper-111.91 ± 20.98 vs 96.33 ± 8.56 μg/dl, p < 0.001; and urine copper-51.70 ± 23.79 vs 36.00 ± 11.70 μg/24 h, p < 0.05. Treatment with metformin for 3 months modified significant erythrocyte magnesium-5.75 ± 0.61 vs 5.09 ± 0.63 mg/dl, p < 0.001 and urine magnesium-198.27 ± 27.07 vs 237.28 ± 34.51 mg/24 h, p < 0.001, whereas it did not modify significant the plasmatic and urinary concentration of the other cations. The erythrocyte magnesium concentration was inversely correlated with HbA1c (r = -0.438, p = 0.015). The plasma level of copper was positively correlated with HbA1c (r = 0.517, p < 0.003), tryglicerides (r = 0.534, p < 0.003), and cholesterol (r = 0.440, p < 0.05), and the plasma level of zinc was inversely correlated with glycemia (r = -0.399, p = 0.029). Our data show a significant action of metformin therapy, by increasing the total intraerythrocyte magnesium concentration and decreasing the urinary magnesium elimination, positively correlated with the decrease of glycemia and HbA1c in NIDDM patients.

Copper, Zinc and Magnesium in Non-Insulin-Dependent Diabetes Mellitus Treated with Metformin

“…(Fig. 5) The results are in accordance with our previous data [49] and with few other results that revealed an increased tissue levels of magnesium associated with metformin treatment. [50] However, our study revealed there is still a decreased intraerythrocyte magnesium level when compared to the control group.…”

The Relationship between Hypomagnesemia, Metformin Therapy and Cardiovascular Disease Complicating Type 2 Diabetes: The Fremantle Diabetes Study

“…Although the evidence from pooled randomized trials has been questioned [10], [11], this recommendation reflects the results of the UK Prospective Diabetes Study (UKPDS), the longest and amongst the largest such trials to date, which showed metformin to have favorable effects on cardiovascular disease independent of blood glucose lowering [12], [13]. If metformin has cardiovascular benefit, or even if its effect is neutral [10], [11], this would appear inconsistent with evidence from human studies that metformin reduces serum magnesium [2], [4], [14], [15] and maintains diabetes-associated hypomagnesemia [3], [16], effects that would theoretically increase vascular risk [5]–[7]. The influence of metformin on magnesium homoeostasis is, however, complex, with evidence of an increase in intracellular magnesium [16], [17] that may offset the potential adverse effects of hypomagnesemia.…”

“…If metformin has cardiovascular benefit, or even if its effect is neutral [10], [11], this would appear inconsistent with evidence from human studies that metformin reduces serum magnesium [2], [4], [14], [15] and maintains diabetes-associated hypomagnesemia [3], [16], effects that would theoretically increase vascular risk [5]–[7]. The influence of metformin on magnesium homoeostasis is, however, complex, with evidence of an increase in intracellular magnesium [16], [17] that may offset the potential adverse effects of hypomagnesemia. In addition, there may be other major influences on magnesium metabolism in diabetic patients, including renal disease, gastrointestinal disorders, and a variety of other drugs that lower serum magnesium including alcohol, diuretics and proton pump inhibitors [18].…”

Iatrogenic hypomagnesemia: an underestimated clinical problem

“…15 Metformin reduces serum magnesium 3,16 and maintains diabetes-associated hypomagnesemia. 17 The influence of metformin on magnesium homeostasis is, however, complex, with evidence of an increase in intracellular magnesium. 17,18 PPIs belong to the most widely prescribed classes of drugs in the world.…”

“…17 The influence of metformin on magnesium homeostasis is, however, complex, with evidence of an increase in intracellular magnesium. 17,18 PPIs belong to the most widely prescribed classes of drugs in the world. In 2006, two cases of PPI-induced hypomagnesemia were published by Epstein and coll.…”