It does not show that metformin causes any heart or thyroid dysfunction ie change in thyroid hormone levels, merely that it reduces TSH in those on thyroid replacement.- indicating that thyroid dose may be able to be tapered.
A parallel new study from Italy Metformin-induced thyrotropin suppression is not associated with cardiac effects confirms there is no heart risk- quite the contrary.
People tend to fatten and slow down as they age, and these people tend to metabolic syndrome ie obesity, cholesterolemia, hypertension, vascular disease and thus diabetes- same as patients with hypothyroidism. So type 2 diabetes, hypothyroidism (sometimes preceded by hyperthyroidism) and aging go together- usually without demonstrable direct cause and effect.
This new McGill University metformin study does not claim any cause and effect. The link may be simply that metformin (which is simply a carbon-hydrogen -nitrogen molecule) improves all metabolic functions- antioxidant, nitric oxidant- including iodine/TRH/ TSH / thyroid/insulin hormone responses. .
it is among other things a prohormone regulator, improving common insulin resistance.
the definition of low TSH is arbitrary. If much below 1, it is suspicious of thyroid overactivity, excess thyroid hormones-
but rarely may reflect central ie pituitary failure to produce enough TRH/TSH and thus cause central hypothyroidism.
so TSH unless way outside the ‘normal’ range of 1 to 2 is a poor guide to health and disease, which is based on clinical state and the thyroid hormone and antibody levels.
Most aging people develop some degrees of thyroid underactivity, which generally responds to replacement of deficient selenium, iodine and sex hormones without addition of risky thyroid hormones- for which conventional blood levels are a poor guide.
so as in all patients whatever their state and treatment, thyroid function should like all other functions be considered periodically.
Metformin and low levels of thyroid-stimulating hormone in patients with type 2 diabetes mellitus McGill University; Montréal, Quebec.
Background: Small cross-sectional studies have suggested that metformin, a first-line oral hypoglycemic agent, may lower thyroid-stimulating hormone (TSH) levels. Our objective was to determine whether the use of metformin monotherapy, when compared with sulfonylurea monotherapy, is associated with an increased risk of low TSH levels (< 0.4 mIU/L) in patients with type 2 diabetes mellitus.
Methods: Using the Clinical Practice Research Datalink, we identified patients who began receiving metformin or sulfonylurea monotherapy between Jan. 1, 1988, and Dec. 31, 2012. We assembled 2 subcohorts of patients with treated hypothyroidism or euthyroidism, and followed them until Mar. 31, 2013. We used Cox proportional hazards models to evaluate the association of low TSH levels with metformin monotherapy, compared with sulfonylurea monotherapy, in each subcohort.
Results: A total of 5689 patients with treated hypothyroidism and 59 937 euthyroid patients were included in the subcohorts. Among patients with treated hypothyroidism, 495 events of low TSH levels were observed during follow-up (incidence rate 119.7/1000 person-years). In the euthyroid group, 322 events of low TSH levels were observed (incidence rate 4.5/1000 person-years). Compared with sulfonylurea monotherapy, metformin monotherapy was associated with a 55% increased risk of low TSH levels in patients with treated hypothyroidism (incidence rate 79.5/1000 person-years v.125.2/1000 person-years, adjusted hazard ratio [HR] 1.55, 95% confidence interval [CI] 1.09–2.20), with the highest risk in the 90–180 days after initiation (adjusted HR 2.30, 95% CI 1.00–5.29). No association was observed in euthyroid patients (adjusted HR 0.97, 95% CI 0.69–1.36).
Interpretation: In this longitudinal population-based study, metformin use was associated with an increased incidence of low TSH levels in patients with treated hypothyroidism, but not in euthyroid patients. The clinical consequences of this need further investigation.
1Department of Medical and Surgical Sciences, Endocrine and Metabolic Unit, University of Brescia; 2Unit of Internal Medicine and Endocrinology, Fondazione Salvatore Maugeri Istituto di Ricovero e Cura a Carattere Scientifico, Istituto Superiore Prevenzione e Sicurezza Lavoro Laboratory for Endocrine Disruptors, University of Pavia; 3Diabetic Unit, Spedali Civili di Brescia; Italy http://www.ncbi.nlm.nih.gov/pubmed/24776625
OBJECTIVE: Metformin treatment may induce a decrease/suppression in serum TSH levels, mimicking sub-clinical hyperthyroidism (SHT). The aim of the present study was to retrospectively evaluate changes in several electrocardiographic indices in euthyroid subjects with diabetes who, after starting metformin treatment, developed a low serum TSH as compared to patients with SHT resulting from an underlying thyroid disease or TSH suppressive treatment with L-thyroxine.
DESIGN: Heart rate, P wave duration, P wave dispersion, QTmax, QTmin and QT-dispersion were assessed in 23 patients with diabetes treated with metformin before and after 6 months of TSH-suppression and in 31 control patients with SHT.
RESULTS: No significant changes in electrocardiographic parameters were observed from baseline to the TSH-suppression measurement. A significant difference in P wave duration (102.9±7.4 vs. 92.1±5.8 ms, p<0.001), P wave dispersion (13.1±3.4 vs. 7.1±3.5 ms, p<0.001), QTmax (399±18 vs. 388±16 ms, p=0.024), QTmin (341±14 vs. 350±17 ms, p=0.038) and QT dispersion (49.9±9.6 vs. 30.9±9.2 ms, p<0.001) were observed between the control group with SHT and the group of diabetic patients with low serum levels of TSH.
CONCLUSIONS: Our results show that the TSH-suppressive effect observed in patients taking metformin is not associated with peripheral markers of thyroid hormone excess, at least at the cardiac level.