Efficacy of Metformin Versus Sitagliptin on Benign Thyroid Nodules Size in Type 2 Diabetes: a 2-years Prospective Multicentric Study
试验速览
- 阶段
- 4 期
- 发起方
- 入组人数
- 90
- 试验地点
- 4
- 主要终点
- 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.
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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
研究组 & 干预措施
Metformin
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.
干预措施: METFORMIN (Drug)
Sitagliptin
In arm 2, sitagliptin will be prescribed at 100mg / day. A classic follow-up will be done every 3 months.
干预措施: Sitagliptin (Drug)
结局指标
主要结局
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.
时间窗: 24 months
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.
次要结局
- 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)
- Plasmatic thyroid hormon levels(Baseline, every 6 months after treatment initiation until 24 months)
- Percentage of IGF-1 receptor expression in thyroid tissues after TN surgery(through study completion, an average of 1 year)
- Percentage of adiponectin receptor expression in thyroid tissues after TN surgery(through study completion, an average of 1 year)
- Proportion of subjects with improvement of adipokine concentrations(Baseline and 24 months after treatment initiation)