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Efficacy of Metformin Versus Sitagliptin on Benign Thyroid Nodules in Type 2 Diabetes (METNODTHYR)

Primary Purpose

Diabetes Mellitus, Type 2, Thyroid Nodule (Benign)

Status

Not yet recruiting

Phase

Phase 4

Locations

International

Study Type

Interventional

Intervention

METFORMIN

Sitagliptin

About this trial

This is an interventional prevention trial for Diabetes Mellitus, Type 2 focused on measuring type 2 diabetes mellitus, thyroid nodule, metformin, insulin resistance

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Patients with T2DM aged 18 to 65 years;
Uncomplicated T2DM, evolving for less than 3 years;
Patients with HbA1c levels between 7 and 8% (after the run-in period)
Patients with at least one TN ≥ 2 cm non-cystic, whose benignity will be confirmed by a fine-needle aspiration cytology performed twice regardless of ultrasound TIRADS score;
Naive subjects of any treatment: never received an anti-diabetic treatment OR received an anti-diabetic treatment of less than 30 days since diagnosis OR did not receive an anti-diabetic treatment during the 30 days before screening;
Patients with a creatinine clearance > 60 ml/min;
Informed and written consent signed by the patient and the investigator;
Affiliation to the national social health system or equivalent.

Exclusion Criteria:

Subjects without adequate or impaired decisional abilities for consent to research and placed under guardianship, trusteeship or safeguard of justice
Pregnant or breastfeeding woman
Woman of childbearing potential without effective contraception (estroprogestative, presentative, intrauterine device)
Suspect thyroid nodules in ultrasound (TIRADS 4 to 5) with confirmation after a fine-needle aspiration cytology;
Thyroid function abnormalities or a history of thyroid disease;
Thyroid nodules whose size or symptoms (compressive signs) require surgery
Ioduria <100ug /L
Thyroid autoimmunity: positive anti-peroxidase, thyroglobulin or anti-TSH receptors antibodies
Levothyroxine treatment
History of cervical radiotherapy or thyroid surgery
Type 1 diabetes
Insulin deficiency
History of hypersensitivity to one of the active substances
History of pancreatitis
Obesity linked to endocrine disease
Presence of severe complications of T2DM (ischemic heart disease, heart failure with reduced left ventricular ejection fraction, severe lower extremity arteritis, gangrene, retinopathy, end-stage renal failure, cerebrovascular accident)
HbA1c levels > 8% after the run-in period
Liver diseases (liver failure, cirrhosis, viral hepatitis B or C)
Acute alcoholic intoxication, chronic alcoholism
Psychiatric diseases (depression, schizophrenia)
Neurological diseases (epilepsy, demyelinating diseases, etc.)
Treatment influencing the morphology or thyroid function: corticosteroids, lithium, iodized products etc. ...
Acute conditions that may impair renal function such as: dehydration, severe infection, shock
Respiratory failure
Metabolic acidosis

Sites / Locations

CHU Bordeaux
CHU Limoges
University Hospital Center of Guadeloupe
CHU de la Réunion

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Metformin

Sitagliptin

Arm Description

In arm 1, the subjects will receive metformin at the initial dose of 500mg x 2 / day, which will be increased weekly to 500mgx3 / day and then 1gx2 / day in order to obtain the minimum effective dose on glycemic control.

In arm 2, sitagliptin will be prescribed at 100mg / day. A classic follow-up will be done every 3 months.

Outcomes

Primary Outcome Measures

Percentage of patients in each group who had at least a 20% decrease in one or more nodules of more than 2 cm at 2 years.

Size : The reduction of TN will be evaluated by thyroid ultrasonography. The operator will be the same throughout the follow-up and in each center, with an evaluation every 6 months. A measurement and precise analysis of the TN will be performed. If a TIRADS 4 or 5 classification is described , a new fine-needle aspiration cytology will be performed. A final thyroid ultrasonography evaluation will be performed at 2 years in order to allow the comparison of TN sizes from the pre-inclusion period to the final period.

Secondary Outcome Measures

Percentage of thyroid surgery observed in each group at 2 years.

Record the number of thyroid surgeries performed after inclusion for 2 years

Number of new TN (≥ 10mm) after 2 years of follow-up

Detection of new TN (≥ 10mm) by thyroid ultrasonography. The operator will be the same throughout the follow-up and in each center

Change between percentage of metabolic syndrome before and after treatment according to the NCEP ATP III definition

Central or abdominal obesity (measured by waist circumference): Men - greater than 40 inches (102 cm) Women - greater than 35 inches (88cm) Triglycerides plasmatic levels greater than or equal to 150 mg/dL (1.7 mmol/L) HDL cholesterol : Men - Less than 40 mg/dL (1.03 mmol/L) Women - Less than 50 mg/dL (1.29 mmol/L) Blood pressure greater than or equal to 130/85 mm Hg Fasting glucose greater than or equal to 110 mg/dL (6.1 mmol/L)

Proportion of subjects with improvement of the HOMA-IR index

The HOMA index will be measured after calculation the ratio between the [fasting plasma insulin (Mu / L) X Fasting plasma glucose (mmol / l)] / 22.5

Proportion of subjects with improvement of adipokine concentrations

Among the adipokines, we will measure the plasmatic Leptin, Adiponectin and Vifastin levels

Plasmatic thyroid hormon levels

these dosages will allow us to evaluate the changes in the functioning of the nodular thyroid gland during follow-up under either treatment

Percentage of IGF-1 receptor expression in thyroid tissues after TN surgery

The analysis of the tissue expression of IGF1 receptors will be performed on thyroid samples after surgery if performed. One sample will be frozen and another will be included in paraffin for further analysis. IGF1 receptors are involved in the insulin and glucose metabolism signaling pathways. Analysis of their expression could help us to understand the possible links between insulin resistance and thyroid nodule.

Percentage of adiponectin receptor expression in thyroid tissues after TN surgery

The analysis of the tissue expression of adiponectin receptor will be performed on thyroid samples after surgery if performed. One sample will be frozen and another will be included in paraffin for further analysis. Adiponectin receptor are involved in the insulin and glucose metabolism signaling pathways. Analysis of their expression could help us to understand the possible links between insulin resistance and thyroid nodule.

Full Information

NCT ID

NCT04298684

First Posted

February 5, 2020

Last Updated

September 10, 2020

Sponsor

Centre Hospitalier Universitaire de Pointe-a-Pitre

1. Study Identification

Unique Protocol Identification Number

NCT04298684

Brief Title

Efficacy of Metformin Versus Sitagliptin on Benign Thyroid Nodules in Type 2 Diabetes

Acronym

METNODTHYR

Official Title

Efficacy of Metformin Versus Sitagliptin on Benign Thyroid Nodules Size in Type 2 Diabetes: a 2-years Prospective Multicentric Study

Study Type

Interventional

2. Study Status

Record Verification Date

September 2020

Overall Recruitment Status

Not yet recruiting

Study Start Date

January 1, 2021 (Anticipated)

Primary Completion Date

February 1, 2022 (Anticipated)

Study Completion Date

July 1, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Centre Hospitalier Universitaire de Pointe-a-Pitre

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

A 2-years prospective, randomized and multicentric study will be performed to assess the efficacy of metformin compared to sitagliptin on benign thyroid nodules size ≥ 2 cm, in newly diagnosed patients with type 2 diabetes.

Detailed Description

Previous studies reported that prevalence of thyroid nodules (TN) is increased in patients with insulin resistance (IR) and type 2 diabetes mellitus (T2DM). However, there are no guidelines for the management of TN in this target population. In 2013, the French National Health Insurance reported that thyroid surgery procedures for benign nodules have increased unjustifiably. The impact of such surgery on the patients could be serious, with psychological repercussions and risks of surgical complications and the need of a substitutive lifetime hormonal treatment. The investigators hypothesize that metformin may reduce the need of TN surgery by decreasing benign TN size through a reduction of IR profile. A 2-years multicentric prospective study will be conducted to compare efficacy of metformin versus sitagliptin on benign thyroid nodules size in patients with initial benign thyroid nodules ≥ 2 cm. The percentage of thyroid surgery avoided, IR profile measured by Homeostasis Model Assessment of Insulin Resistance-Index (HOMA-IR-index) and adipokines concentrations will be also collected at inclusion ad at 2 years. The Primary outcome will be the percentage of patients in each group who had at least a 20% decrease in one or more nodules of more than 2 cm at 2 years. Several secondary outcomes will be registered: percentage of thyroid surgery observed in each group at 2 years, number of new TN (≥ 10mm) after 2 years of follow-up , percentage of metabolic syndrome before and after treatment, proportion of subjects with improvement of the HOMA-IR index and adipokine concentrations, plasmatic thyroid-stimulating hormone (TSH), T4 and T3 levels evolution, percentage of insulin like growth factor-1 (IGF-1) and adiponectin receptor expression in thyroid tissues after TN surgery.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Diabetes Mellitus, Type 2, Thyroid Nodule (Benign)

Keywords

type 2 diabetes mellitus, thyroid nodule, metformin, insulin resistance

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Model Description

Multicenter, prospective open-label study evaluating the efficacy of metformin compared to sitagliptin on benign TN growth in subjects with T2DM. After written approval, subjects with T2DM who meet the eligibility criteria will have a thyroid ultrasound. Subjects with TN of at least 2 cm and 2 benign cytology results after fine-needle aspiration, will be included after a run-in period of 1 month with a daily basal insulin therapy in order to reduce glucotoxicity. If the Hb1Ac levels remain above 8%, the subjects will not be included. After inclusion, a central randomization will allow subjects to benefit from either metformin (group 1) or sitagliptin (group 2). In both cases, the standard nutritional care and physical activity recommendations (150 minutes of physical activity per week) will be recalled. If HbA1c levels > 8% during the follow-up, treatment by gliclazide will be introduce (LP30mg). A follow-up schedule will be given to the included patient for future visits.

Masking

None (Open Label)

Allocation

Randomized

Enrollment

90 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Metformin

Arm Type

Experimental

Arm Description

Arm Title

Sitagliptin

Arm Type

Placebo Comparator

Arm Description

In arm 2, sitagliptin will be prescribed at 100mg / day. A classic follow-up will be done every 3 months.

Intervention Type

Drug

Intervention Name(s)

METFORMIN

Intervention Description

After inclusion, a central randomization will allow subjects to benefit from either metformin (group 1) or sitagliptin (group 2). A follow-up schedule will be given to the included patient for future visits. thyroid ultrasonography to analyze the TN evolution in the 2 groups. In arm 1, the subjects will receive metformin at the initial dose of 500mg x 2 / day, which will be increased weekly to 500mgx3 / day and then 1gx2 / day in order to obtain the minimum effective dose on glycemic control. In case of intolerance, the tolerated and effective dose will be taken back provided an effective glycemic control. A classic follow-up will be done every 3 months. Thyroid US and measure of HOMA-IR index will be done every 6 months for 2 years. If the goal of HbA1c will not achieved, a treatment with glicazide will be introduced.

Intervention Type

Drug

Intervention Name(s)

Sitagliptin

Intervention Description

Primary Outcome Measure Information:

Title

Percentage of patients in each group who had at least a 20% decrease in one or more nodules of more than 2 cm at 2 years.

Description

Time Frame

24 months

Secondary Outcome Measure Information:

Title

Percentage of thyroid surgery observed in each group at 2 years.

Description

Record the number of thyroid surgeries performed after inclusion for 2 years

Time Frame

24 months after treatment initiation

Title

Number of new TN (≥ 10mm) after 2 years of follow-up

Description

Detection of new TN (≥ 10mm) by thyroid ultrasonography. The operator will be the same throughout the follow-up and in each center

Time Frame

Baseline and 24 months after treatment initiation

Title

Change between percentage of metabolic syndrome before and after treatment according to the NCEP ATP III definition

Description

Time Frame

Baseline, every 6 months after treatment initiation until 24 months

Title

Proportion of subjects with improvement of the HOMA-IR index

Description

The HOMA index will be measured after calculation the ratio between the [fasting plasma insulin (Mu / L) X Fasting plasma glucose (mmol / l)] / 22.5

Time Frame

Baseline, every 6 months after treatment initiation until 24 months

Title

Proportion of subjects with improvement of adipokine concentrations

Description

Among the adipokines, we will measure the plasmatic Leptin, Adiponectin and Vifastin levels

Time Frame

Baseline and 24 months after treatment initiation

Title

Plasmatic thyroid hormon levels

Description

these dosages will allow us to evaluate the changes in the functioning of the nodular thyroid gland during follow-up under either treatment

Time Frame

Baseline, every 6 months after treatment initiation until 24 months

Title

Percentage of IGF-1 receptor expression in thyroid tissues after TN surgery

Description

Time Frame

through study completion, an average of 1 year

Title

Percentage of adiponectin receptor expression in thyroid tissues after TN surgery

Description

Time Frame

through study completion, an average of 1 year

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Patients with T2DM aged 18 to 65 years; Uncomplicated T2DM, evolving for less than 3 years; Patients with HbA1c levels between 7 and 8% (after the run-in period) Patients with at least one TN ≥ 2 cm non-cystic, whose benignity will be confirmed by a fine-needle aspiration cytology performed twice regardless of ultrasound TIRADS score; Naive subjects of any treatment: never received an anti-diabetic treatment OR received an anti-diabetic treatment of less than 30 days since diagnosis OR did not receive an anti-diabetic treatment during the 30 days before screening; Patients with a creatinine clearance > 60 ml/min; Informed and written consent signed by the patient and the investigator; Affiliation to the national social health system or equivalent. Exclusion Criteria: Subjects without adequate or impaired decisional abilities for consent to research and placed under guardianship, trusteeship or safeguard of justice Pregnant or breastfeeding woman Woman of childbearing potential without effective contraception (estroprogestative, presentative, intrauterine device) Suspect thyroid nodules in ultrasound (TIRADS 4 to 5) with confirmation after a fine-needle aspiration cytology; Thyroid function abnormalities or a history of thyroid disease; Thyroid nodules whose size or symptoms (compressive signs) require surgery Ioduria <100ug /L Thyroid autoimmunity: positive anti-peroxidase, thyroglobulin or anti-TSH receptors antibodies Levothyroxine treatment History of cervical radiotherapy or thyroid surgery Type 1 diabetes Insulin deficiency History of hypersensitivity to one of the active substances History of pancreatitis Obesity linked to endocrine disease Presence of severe complications of T2DM (ischemic heart disease, heart failure with reduced left ventricular ejection fraction, severe lower extremity arteritis, gangrene, retinopathy, end-stage renal failure, cerebrovascular accident) HbA1c levels > 8% after the run-in period Liver diseases (liver failure, cirrhosis, viral hepatitis B or C) Acute alcoholic intoxication, chronic alcoholism Psychiatric diseases (depression, schizophrenia) Neurological diseases (epilepsy, demyelinating diseases, etc.) Treatment influencing the morphology or thyroid function: corticosteroids, lithium, iodized products etc. ... Acute conditions that may impair renal function such as: dehydration, severe infection, shock Respiratory failure Metabolic acidosis

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Valerie VS HAMONY SOTER

Phone

+590590934686

valerie.soter@chu-guadeloupe.fr

First Name & Middle Initial & Last Name or Official Title & Degree

Mélanie MP PETAPERMAL

melanie.petapermal@chu-guadeloupe.fr

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Fritz-Line FLV VELAYOUDOM, MD

Organizational Affiliation

CHU de la Guadeloupe

Official's Role

Study Director

Facility Information:

Facility Name

CHU Bordeaux

City

Bordeaux

ZIP/Postal Code

33000

Country

France

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Bogdan BC CATARGI, MD PhD

bogdan.catargi@chu-bordeaux.fr

Facility Name

CHU Limoges

City

Limoges

ZIP/Postal Code

87042

Country

France

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Marie-Pierre MT TEISSIER, M.D. Ph D

Phone

+335 55 05 68 51

marie-pierre.teissier@chu-limoges.fr

Facility Name

University Hospital Center of Guadeloupe

City

Pointe-à-Pitre

ZIP/Postal Code

97159

Country

Guadeloupe

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Valérie VS SOTER, Project Manager

Phone

0590 93 46 86

valerie.soter@chu-guadeloupe.fr

First Name & Middle Initial & Last Name & Degree

Melanie MP PETAPERMAL, Monito manager

Phone

0590 93 46 86

melanie.eptapermal@chu-guadeloupe.fr

First Name & Middle Initial & Last Name & Degree

Fritz-Line FV VELAYOUDOM, M. D. PHD HDR

Facility Name

CHU de la Réunion

City

Saint-Pierre

ZIP/Postal Code

97400

Country

Réunion

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Xavier XD DEBUSSCHE, MD PHD

xavier.debussche@chu-reunion.fr

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

23395200

Citation

Anil C, Akkurt A, Ayturk S, Kut A, Gursoy A. Impaired glucose metabolism is a risk factor for increased thyroid volume and nodule prevalence in a mild-to-moderate iodine deficient area. Metabolism. 2013 Jul;62(7):970-5. doi: 10.1016/j.metabol.2013.01.009. Epub 2013 Feb 5.

Results Reference

background

PubMed Identifier

19633072

Citation

Ayturk S, Gursoy A, Kut A, Anil C, Nar A, Tutuncu NB. Metabolic syndrome and its components are associated with increased thyroid volume and nodule prevalence in a mild-to-moderate iodine-deficient area. Eur J Endocrinol. 2009 Oct;161(4):599-605. doi: 10.1530/EJE-09-0410. Epub 2009 Jul 24.

Results Reference

background

PubMed Identifier

20578900

Citation

Barbesino G. Drugs affecting thyroid function. Thyroid. 2010 Jul;20(7):763-70. doi: 10.1089/thy.2010.1635.

Results Reference

background

PubMed Identifier

27987248

Citation

Bonnet F, Scheen A. Understanding and overcoming metformin gastrointestinal intolerance. Diabetes Obes Metab. 2017 Apr;19(4):473-481. doi: 10.1111/dom.12854. Epub 2017 Feb 22.

Results Reference

background

PubMed Identifier

22278418

Citation

Chen G, Xu S, Renko K, Derwahl M. Metformin inhibits growth of thyroid carcinoma cells, suppresses self-renewal of derived cancer stem cells, and potentiates the effect of chemotherapeutic agents. J Clin Endocrinol Metab. 2012 Apr;97(4):E510-20. doi: 10.1210/jc.2011-1754. Epub 2012 Jan 25.

Results Reference

background

PubMed Identifier

2480830

Citation

Clemmons DR. Structural and functional analysis of insulin-like growth factors. Br Med Bull. 1989 Apr;45(2):465-80. doi: 10.1093/oxfordjournals.bmb.a072335.

Results Reference

background

PubMed Identifier

19860577

Citation

American Thyroid Association (ATA) Guidelines Taskforce on Thyroid Nodules and Differentiated Thyroid Cancer; Cooper DS, Doherty GM, Haugen BR, Kloos RT, Lee SL, Mandel SJ, Mazzaferri EL, McIver B, Pacini F, Schlumberger M, Sherman SI, Steward DL, Tuttle RM. Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid. 2009 Nov;19(11):1167-214. doi: 10.1089/thy.2009.0110. Erratum In: Thyroid. 2010 Aug;20(8):942. Hauger, Bryan R [corrected to Haugen, Bryan R]. Thyroid. 2010 Jun;20(6):674-5.

Results Reference

background

PubMed Identifier

25734734

Citation

Durante C, Costante G, Lucisano G, Bruno R, Meringolo D, Paciaroni A, Puxeddu E, Torlontano M, Tumino S, Attard M, Lamartina L, Nicolucci A, Filetti S. The natural history of benign thyroid nodules. JAMA. 2015 Mar 3;313(9):926-35. doi: 10.1001/jama.2015.0956.

Results Reference

background

PubMed Identifier

26154837

Citation

Hazel-Fernandez L, Xu Y, Moretz C, Meah Y, Baltz J, Lian J, Kimball E, Bouchard J. Historical cohort analysis of treatment patterns for patients with type 2 diabetes initiating metformin monotherapy. Curr Med Res Opin. 2015;31(9):1703-16. doi: 10.1185/03007995.2015.1067194. Epub 2015 Aug 27.

Results Reference

background

PubMed Identifier

16950706

Citation

Junik R, Kozinski M, Debska-Kozinska K. Thyroid ultrasound in diabetic patients without overt thyroid disease. Acta Radiol. 2006 Sep;47(7):687-91. doi: 10.1080/02841850600806308.

Results Reference

background

PubMed Identifier

9839117

Citation

Levy JC, Matthews DR, Hermans MP. Correct homeostasis model assessment (HOMA) evaluation uses the computer program. Diabetes Care. 1998 Dec;21(12):2191-2. doi: 10.2337/diacare.21.12.2191. No abstract available.

Results Reference

background

PubMed Identifier

29858981

Citation

Liu MZ, He HY, Luo JQ, He FZ, Chen ZR, Liu YP, Xiang DX, Zhou HH, Zhang W. Drug-induced hyperglycaemia and diabetes: pharmacogenomics perspectives. Arch Pharm Res. 2018 Jul;41(7):725-736. doi: 10.1007/s12272-018-1039-x. Epub 2018 Jun 1.

Results Reference

background

PubMed Identifier

3899825

Citation

Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985 Jul;28(7):412-9. doi: 10.1007/BF00280883.

Results Reference

background

PubMed Identifier

12525244

Citation

Menendez C, Baldelli R, Camina JP, Escudero B, Peino R, Dieguez C, Casanueva FF. TSH stimulates leptin secretion by a direct effect on adipocytes. J Endocrinol. 2003 Jan;176(1):7-12. doi: 10.1677/joe.0.1760007.

Results Reference

background

PubMed Identifier

28196954

Citation

Meng X, Xu S, Chen G, Derwahl M, Liu C. Metformin and thyroid disease. J Endocrinol. 2017 Apr;233(1):R43-R51. doi: 10.1530/JOE-16-0450. Epub 2017 Feb 14.

Results Reference

background

PubMed Identifier

15562188

Citation

Pladevall M, Williams LK, Potts LA, Divine G, Xi H, Lafata JE. Clinical outcomes and adherence to medications measured by claims data in patients with diabetes. Diabetes Care. 2004 Dec;27(12):2800-5. doi: 10.2337/diacare.27.12.2800.

Results Reference

background

PubMed Identifier

19320560

Citation

Rezzonico JN, Rezzonico M, Pusiol E, Pitoia F, Niepomniszcze H. Increased prevalence of insulin resistance in patients with differentiated thyroid carcinoma. Metab Syndr Relat Disord. 2009 Aug;7(4):375-80. doi: 10.1089/met.2008.0062.

Results Reference

background

PubMed Identifier

18346005

Citation

Rezzonico J, Rezzonico M, Pusiol E, Pitoia F, Niepomniszcze H. Introducing the thyroid gland as another victim of the insulin resistance syndrome. Thyroid. 2008 Apr;18(4):461-4. doi: 10.1089/thy.2007.0223.

Results Reference

background

PubMed Identifier

30233494

Citation

Sui M, Yu Y, Zhang H, Di H, Liu C, Fan Y. Efficacy of Metformin for Benign Thyroid Nodules in Subjects With Insulin Resistance: A Systematic Review and Meta-Analysis. Front Endocrinol (Lausanne). 2018 Aug 28;9:494. doi: 10.3389/fendo.2018.00494. eCollection 2018.

Results Reference

background

PubMed Identifier

29158735

Citation

Tang Y, Yan T, Wang G, Chen Y, Zhu Y, Jiang Z, Yang M, Li C, Li Z, Yu P, Wang S, Zhu N, Ren Q, Ni C. Correlation between Insulin Resistance and Thyroid Nodule in Type 2 Diabetes Mellitus. Int J Endocrinol. 2017;2017:1617458. doi: 10.1155/2017/1617458. Epub 2017 Oct 12.

Results Reference

background

PubMed Identifier

11376121

Citation

Vella V, Sciacca L, Pandini G, Mineo R, Squatrito S, Vigneri R, Belfiore A. The IGF system in thyroid cancer: new concepts. Mol Pathol. 2001 Jun;54(3):121-4. doi: 10.1136/mp.54.3.121.

Results Reference

background

PubMed Identifier

22232784

Citation

Wemeau JL, Sadoul JL, d'Herbomez M, Monpeyssen H, Tramalloni J, Leteurtre E, Borson-Chazot F, Caron P, Carnaille B, Leger J, Do Cao C, Klein M, Raingeard I, Desailloud R, Leenhardt L; French Society of Endocrinology. [Recommendations of the French Society of Endocrinology for the management of thyroid nodules]. Presse Med. 2011 Sep;40(9 Pt 1):793-826. No abstract available. French.

Results Reference

background

PubMed Identifier

24927125

Citation

Yeo Y, Ma SH, Hwang Y, Horn-Ross PL, Hsing A, Lee KE, Park YJ, Park DJ, Yoo KY, Park SK. Diabetes mellitus and risk of thyroid cancer: a meta-analysis. PLoS One. 2014 Jun 13;9(6):e98135. doi: 10.1371/journal.pone.0098135. eCollection 2014.

Results Reference

background

PubMed Identifier

18165338

Citation

American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care. 2008 Jan;31 Suppl 1:S55-60. doi: 10.2337/dc08-S055. No abstract available.

Results Reference

background

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Efficacy of Metformin Versus Sitagliptin on Benign Thyroid Nodules in Type 2 Diabetes

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