Generic placeholder image

Current Pharmaceutical Design

Editor-in-Chief

ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

General Review Article

The Effect of Metformin on Thyroid-Associated Serum Hormone Levels and Physiological Indexes: A Meta-Analysis

Author(s): Junjie Wang , Jinghan Gao, Qin Fan, Hongzhuo Li and Yunhua Di*

Volume 25, Issue 30, 2019

Page: [3257 - 3265] Pages: 9

DOI: 10.2174/1381612825666190918162649

Price: $65

Abstract

Background: Many diseases can be treated with metformin. People with serum thyrotropin (TSH) levels higher than 10 mIU/L are at a risk of cardiovascular events. Some studies have suggested that metformin can lower serum TSH levels to a subnormal level in patients with hyperthyrotropinaemia or hypothyroidism.

Objective: The objective of this analysis is to evaluate the effect of metformin treatment on serum TSH, free triiodothyronine (FT3), and free thyroxine (FT4) levels and other associated physiological indices.

Methods: A comprehensive search using the PubMed, EMBASE, Web of Science and Cochrane Central databases was undertaken for controlled trials on the effect of metformin on serum TSH, FT3, and FT4 levels and associated physiological indices. The primary outcome measures were serum TSH, FT3 and FT4 levels, thyroid size, thyroid nodule size, blood pressure, heart rate, body weight, and body mass index (BMI). The final search was conducted in April 2019.

Results: Six RCTs were included. A total of 494 patients met the inclusion criteria. Metformin treatment did not significantly lower the serum TSH levels at 3 or 6 months but did at 12 months. Moreover, forest plots also suggested that metformin can significantly lower the serum TSH levels in patients with normal thyroid function but cannot statistically change the serum TSH levels in patients with abnormal thyroid function. In addition, metformin treatment clearly lowered the serum FT3 levels and had no significant effect on serum FT4 levels. Lastly, metformin cannot significantly change the systolic blood pressure (SBP) or BMI but can clearly increase the diastolic blood pressure (DBP).

Conclusion: Metformin treatment can significantly lower the serum TSH levels, and this effect was much clearer after a 12-month treatment duration and in people with normal thyroid function. However, metformin cannot significantly change the serum FT4 levels or lower serum FT3 levels in people with non-thyroid cancer diseases. In addition, metformin can significantly increase DBP, but it has no clear effect on SBP or BMI.

Keywords: Metformin, thyrotropin, hypothyroidism, meta-analysis, cardiovascular events, hyperthyrotropinaemia.

[1]
Shimizu T, Nathan DM, Buse JB, et al. Medical management of hyperglycemia in type 2 diabetes: A consensus algorithm for the initiation and adjustment of therapy: A consensus statement of the American Diabetes Association and the European Association for the study of diabetes. Nihon Rinsho 2012; 70(Suppl. 3): 591-601.
[PMID: 22768584]
[2]
Andújar-Plata P, Pi-Sunyer X, Laferrère B. Metformin effects revisited. Diabetes Res Clin Pract 2012; 95(1): 1-9.
[http://dx.doi.org/10.1016/j.diabres.2011.09.022] [PMID: 22000494]
[3]
D’Ambrosio V, Brunelli R, Vena F, et al. Metformin reduces maternal weight gain in obese pregnant women: A systematic review and meta-analysis of two randomized controlled trials. Diabetes Metab Res Rev 2019; 35(6)e3164
[http://dx.doi.org/10.1002/dmrr.3164]
[4]
Faria J, Negalha G, Azevedo A, Martel F. Metformin and breast cancer: Molecular Targets 2019.
[5]
Courtois S, Lehours P, Bessède E. The therapeutic potential of metformin in gastric cancer. Gastric Cancer 2019; 22(4): 653-62.
[http://dx.doi.org/10.1007/s10120-019-00952-w] [PMID: 30900101]
[6]
Zolfagharzadeh M, Pirouzi M, Asoodeh A, Saberi MR, Chamani J. A comparison investigation of DNP-binding effects to HSA and HTF by spectroscopic and molecular modeling techniques. J Biomol Struct Dyn 2014; 32(12): 1936-52.
[http://dx.doi.org/10.1080/07391102.2013.843062] [PMID: 24125112]
[7]
Sharif-Barfeh Z, Beigoli S, Marouzi S, et al. Multi-spectroscopic and HPLC studies of the interaction between estradiol and cyclophosphamide with human serum albumin. Binary and Ternary Sys J Sol Chem 2017; 46(2): 488-504.
[http://dx.doi.org/10.1007/s10953-017-0590-2]
[8]
Rahnama E, Mahmoodian-Moghaddam M, Khorsand-Ahmadi S, Saberi MR, Chamani J. Binding site identification of metformin to human serum albumin and glycated human serum albumin by spectroscopic and molecular modeling techniques: A comparison study. J Biomol Struct Dyn 2015; 33(3): 513-33.
[http://dx.doi.org/10.1080/07391102.2014.893540] [PMID: 24720899]
[9]
Sanei H, Asoodeh A, Hamedakbari-Tusi S, Chamani J. Multi-spectroscopic investigations of aspirin and colchicine interactions with human hemoglobin. Binary and Ternary Sys J Sol Chem 2011; 40(11): 1905-31.
[http://dx.doi.org/10.1007/s10953-011-9766-3]
[10]
Caton PW, Nayuni NK, Kieswich J, Khan NQ, Yaqoob MM, Corder R. Metformin suppresses hepatic gluconeogenesis through induction of SIRT1 and GCN5. J Endocrinol 2010; 205(1): 97-106.
[http://dx.doi.org/10.1677/JOE-09-0345] [PMID: 20093281]
[11]
Abdulrahman RM, Boon MR, Sips HC, et al. Impact of Metformin and compound C on NIS expression and iodine uptake in vitro and in vivo: A role for CRE in AMPK modulation of thyroid function. Thyroid 2014; 24(1): 78-87.
[http://dx.doi.org/10.1089/thy.2013.0041] [PMID: 23819433]
[12]
Baskin HJ, Cobin RH, Duick DS, et al. American Association of Clinical Endocrinologists medical guidelines for clinical practice for the evaluation and treatment of hyperthyroidism and hypothyroidism. Endocr Pract 2002; 8(6): 457-69.
[http://dx.doi.org/10.4158/1934-2403-8.6.457]
[13]
Cappelli C, Rotondi M, Pirola I, et al. Thyreotropin levels in diabetic patients on metformin treatment. Eur J Endocrinol 2012; 167(2): 261-5.
[http://dx.doi.org/10.1530/EJE-12-0225] [PMID: 22645202]
[14]
Rezzónico J, Rezzónico M, Pusiol E, Pitoia F, Niepomniszcze H. Metformin treatment for small benign thyroid nodules in patients with insulin resistance. Metab Syndr Relat Disord 2011; 9(1): 69-75.
[http://dx.doi.org/10.1089/met.2010.0026] [PMID: 21128816]
[15]
Oleandri SE, Maccario M, Rossetto R, et al. Three-month treatment with metformin or dexfenfluramine does not modify the effects of diet on anthropometric and endocrine-metabolic parameters in abdominal obesity. J Endocrinol Invest 1999; 22(2): 134-40.
[http://dx.doi.org/10.1007/BF03350893] [PMID: 10195381]
[16]
Mousavi Z, Dourandish L, Rokni H, Sadeghi R, Rasoul Zakavi S. Effects of short-term metformin therapy associated with levothyroxine dose decrement on TSH and thyroid hormone levels in patients with thyroid cancer. Minerva Endocrinol 2014; 39(1): 59-65.
[PMID: 24513605]
[17]
Lupoli R, Di Minno A, Tortora A, Ambrosino P, Lupoli GA, Di Minno MN. Effects of treatment with metformin on TSH levels: A meta-analysis of literature studies. J Clin Endocrinol Metab 2014; 99(1): E143-8.
[http://dx.doi.org/10.1210/jc.2013-2965] [PMID: 24203069]
[18]
He X, Wu D, Hu C, et al. Role of metformin in the treatment of patients with thyroid nodules and insulin resistance: A systematic review and meta-analysis thyroid 2019; 29(3): 359-67.
[http://dx.doi.org/10.1089/thy.2017.0707]
[19]
Shuster JJ. Review: Cochrane handbook for systematic reviews for interventions, Version 510, published 3/2011. Julian P.T. Higgins and Sally Green Editors Research Synthesis Methods. 2011; 2: pp. (2)126-30.
[20]
Wells G, Shea B, O'Connell J, et al. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in metaanalyses
[21]
Morteza Taghavi S, Rokni H, Fatemi S. Metformin decreases thyrotropin in overweight women with polycystic ovarian syndrome and hypothyroidism. Diab Vasc Dis Res 2011; 8(1): 47-8.
[http://dx.doi.org/10.1177/1479164110391917] [PMID: 21262871]
[22]
Dornelles Severo M, Stürmer Andrade T, Correa Junior V, Antonio Naujorks A, Gus M, Schaan BD. Metformin effect on TSH in subclinical hypothyroidism: randomized, double-blind, placebo-controlled clinical trial. Endocrine 2018; 59(1): 66-71.
[http://dx.doi.org/10.1007/s12020-017-1462-7] [PMID: 29080044]
[23]
Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ 1997; 315(7109): 629-34.
[http://dx.doi.org/10.1136/bmj.315.7109.629] [PMID: 9310563]
[24]
Duntas LH, Orgiazzi J, Brabant G. The interface between thyroid and diabetes mellitus. Clin Endocrinol (Oxf) 2011; 75(1): 1-9.
[http://dx.doi.org/10.1111/j.1365-2265.2011.04029.x] [PMID: 21521298]
[25]
Manolis AA, Manolis TA, Melita H, Manolis AS. Subclinical thyroid dysfunction and cardiovascular consequences: An alarming wake-up call? Trends Cardiovasc Med 2019; S1050-1738(19): 30029-5.
[http://dx.doi.org/10.1016/j.tcm.2019.02.011] [PMID: 30871865]
[26]
Zhou L, Liu H, Wen X, Peng Y, Tian Y, Zhao L. Effects of metformin on blood pressure in nondiabetic patients: A meta-analysis of randomized controlled trials. J Hypertens 2017; 35(1): 18-26.
[http://dx.doi.org/10.1097/HJH.0000000000001119] [PMID: 27607453]
[27]
Hui F, Zhang Y, Ren T, Li X, Zhao M, Zhao Q. Role of metformin in overweight and obese people without diabetes: a systematic review and network meta-analysis. Eur J Clin Pharmacol 2019; 75(4): 437-50.
[http://dx.doi.org/10.1007/s00228-018-2593-3] [PMID: 30511328]
[28]
Gursoy A. Rising thyroid cancer incidence in the world might be related to insulin resistance. Med Hypotheses 2010; 74(1): 35-6.
[http://dx.doi.org/10.1016/j.mehy.2009.08.021] [PMID: 19720470]
[29]
Rezzónico JN, Rezzónico M, Pusiol E, Pitoia F, Niepomniszcze H. Increased prevalence of insulin resistance in patients with differentiated thyroid carcinoma. Metab Syndr Relat Disord 2009; 7(4): 375-80.
[http://dx.doi.org/10.1089/met.2008.0062] [PMID: 19320560]
[30]
Wu T, Trahair LG, Little TJ, et al. Effects of vildagliptin and metformin on blood pressure and heart rate responses to small intestinal glucose in type 2 diabetes. Diabetes Care 2017; 40(5): 702-5.
[http://dx.doi.org/10.2337/dc16-2391] [PMID: 28258090]
[31]
Das S, Behera SK, Srinivasan A, et al. Effect of metformin on exercise capacity: A meta-analysis. Diabetes Res Clin Pract 2018; 144: 270-8.
[http://dx.doi.org/10.1016/j.diabres.2018.08.022] [PMID: 30217594]
[32]
Chamani J, Heshmati M. Mechanism for stabilization of the molten globule state of papain by sodium n-alkyl sulfates: Spectroscopic and calorimetric approaches. J Colloid Interface Sci 2008; 322(1): 119-27.
[http://dx.doi.org/10.1016/j.jcis.2008.03.001] [PMID: 18405913]
[33]
Moradi N, Ashrafi Kooshk M, Chamani J, Shackebaei D, Norouzi F. Separate and simultaneous binding of tamoxifen and estradiol to human serum albumin: Spectroscopic and molecular modeling investigations. J Mol Liq 2017; 249: 1083-96.
[34]
Mokaberi P, Reyhani V, Amiri-Tehranizadeh Z, et al. New insights into the binding behavior of lomefloxacin and human hemoglobin using biophysical techniques: binary and ternary approaches. New J Chem 2019; 43(21): 8132-45.
[http://dx.doi.org/10.1039/C9NJ01048C]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy