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

NCT04298684 | Unknown Phase 4

• 2 other identifiers: PAP_RI1_2019/12019-000676-42
• Study Type: interventional
• Target: 90
• Locations: 3 countries
• Sites: 4

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.

Conditions

Diabetes Mellitus, Type 2; Thyroid Nodule (Benign)

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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.

  24 months

Secondary Outcomes (8)

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

  24 months after treatment initiation

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

  Baseline and 24 months after treatment initiation

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

  Baseline, every 6 months after treatment initiation until 24 months

• Proportion of subjects with improvement of the HOMA-IR index

  Baseline, every 6 months after treatment initiation until 24 months

• Proportion of subjects with improvement of adipokine concentrations

  Baseline and 24 months after treatment initiation

Study Arms (2)

Metformin

EXPERIMENTAL

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.

Drug: METFORMIN

Sitagliptin

PLACEBO COMPARATOR

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

Drug: Sitagliptin

Interventions

METFORMIN DRUG

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.

Metformin

Sitagliptin DRUG

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 2, sitagliptin will be prescribed at 100mg / day. 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.

Sitagliptin

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Centre Hospitalier Universitaire de la Guadeloupe: lead

Study Sites (4)

CHU Bordeaux

Bordeaux, 33000, France

Location

CHU Limoges

Limoges, 87042, France

Location

University Hospital Center of Guadeloupe

Pointe-à-Pitre, 97159, Guadeloupe

Location

CHU de la Réunion

Saint-Pierre, 97400, Reunion

Location

Related Publications (24)

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MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Thyroid Nodule; Insulin Resistance

Interventions

Metformin; Sitagliptin Phosphate

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Thyroid Neoplasms; Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Thyroid Diseases; Hyperinsulinism

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrazines

Study Officials

• Fritz-Line FLV VELAYOUDOM, MD

  CHU de la Guadeloupe

  STUDY DIRECTOR

Central Study Contacts

Valerie VS HAMONY SOTER

CONTACT

+590590934686; valerie.soter@chu-guadeloupe.fr

Mélanie MP PETAPERMAL

CONTACT

melanie.petapermal@chu-guadeloupe.fr

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: February 5, 2020
• First Posted: March 6, 2020
• Study Start: January 1, 2021
• Primary Completion: February 1, 2022
• Study Completion: July 1, 2024
• Last Updated: September 11, 2020

Record last verified: 2020-09

Data Sharing

• IPD Sharing: Will not share

Locations

FR (2); GU (1); RE (1)