Extending Time Without Diabetes After Bariatric Surgery: a Randomized Controlled Trial Comparing the Metformin Addition or Not to Standard Care
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 126
- 试验地点
- 16
- 主要终点
- Proportion of patients with partial or complete T2D remission criteria
研究概览
简要总结
This study is a randomized trial that evaluates the effect of metformin addition or not to standard care on the duration of diabetes remission after bariatric surgery.
详细描述
In addition to significant weight loss, several randomized control trials (RCTs) have demonstrated that bariatric surgery can reverse or at least improve type 2 diabetes (T2D). Despite the variability in study design and patient characteristics of these RCTs, there is a consistent favorable effect of surgery compared to medical treatment for weight loss, change in HbA1c, reduction in diabetes medications, remission of metabolic syndrome and improvement in quality of life. Diabetes remission rate is estimated from 15 to 45 % according to the 4 available RCT including the most used surgery (Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG)) with at least three to five years of follow-up. These results mean that more than half of patients with type 2 diabetes are still or newly diagnosed with diabetic after surgery and that extending time of diabetes remission after bariatric surgery is of major concern.
No RCT has explored yet an intervention to extend diabetes remission. Apart from bariatric surgery, metformin is unequivocally recommended to treat both diabetes and pre-diabetes along with lifestyle interventions. Results of the Diabetes Prevention Program trial showed that metformin reduces diabetes incidence by 31% in obese patients with pre-diabetes. We hypothesized that metformin might extend the duration of diabetes remission after bariatric surgery.
The study is a randomized, controlled, open-labeled, multicenter trial.
Patients fulfilling the inclusion criteria and without any of the exclusion criteria will be randomized.
Patients will receive:
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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adults 18-70 years old
- •Having undergone gastric bypass or sleeve gastrectomy 12 to 36 +/-3 months before inclusion
- •"ex-T2D" treated with at least one anti-diabetic drug before bariatric surgery or HbA1c ≥ 6.5 % before bariatric surgery
- •HbA1C < 6.5 % at inclusion with no anti-hyperglycemic medications for the last three months
- •Written consent
排除标准
- •Known type 1 diabetes
- •Pregnancy and breastfeeding
- •Estimated glomerular filtration rate<44 ml/min (MDRD)
- •Known intolerance to metformin
- •Known contraindication to metformin:
- •Acute metabolic acidosis
- •Acute affection which could lead to renal deterioration (ex: dehydration, serious infection, shock, intravascular administration of iodinated contrast agent within the last 48 hours)
- •Acute or chronic disease which could lead to a tissue hypoxia (ex : severe cardiac insufficiency, severe respiratory insufficiency, myocardial infarction within the last 3 months, shock)
- •Hepatocellular insufficiency
- •Prothrombin ratio ≤ 50%
- •SGOT or SGPT levels ≥ 10 times the upper limits of the normal range
- •Alcohol use disorder
- •Medications and medical conditions likely to confound the assessment of diabetes:
- •glucocorticoids treatment
- •renal graft
- •Cushing's syndrome
- •acromegaly
- •fasting plasma triglyceride > 600 mg/dl despite treatment
- •Patient under legal protection
研究组 & 干预措施
Metformin + Standard care
The pharmacological treatment (Metformin) will start at dose of 850 mg once daily and, at one month, increased to 850 mg twice daily. The dosage will be adjusted if necessary because of gastrointestinal symptoms and information on dose change during follow-up will be collected Adherence to study medications will be assessed by pills count and plasmatic dosage (Metformin group).
All participants will receive standardized lifestyle recommendations regularly during all the time of the study Lifestyle recommendations will be provided by a nutritionist/diabetologist every 6 months at each study visit and reinforced by dedicated consultations with a dietician and a physical activity coach as usually performed in each center. This follow-up will be standardized for each center and applied equally to patients of both groups.
Ancillary study measuring metformin-induced enterohormones secretion will be performed on a subgroup of 30 patients randomized in this arm.
干预措施: Metformin (Drug)
Metformin + Standard care
The pharmacological treatment (Metformin) will start at dose of 850 mg once daily and, at one month, increased to 850 mg twice daily. The dosage will be adjusted if necessary because of gastrointestinal symptoms and information on dose change during follow-up will be collected Adherence to study medications will be assessed by pills count and plasmatic dosage (Metformin group).
All participants will receive standardized lifestyle recommendations regularly during all the time of the study Lifestyle recommendations will be provided by a nutritionist/diabetologist every 6 months at each study visit and reinforced by dedicated consultations with a dietician and a physical activity coach as usually performed in each center. This follow-up will be standardized for each center and applied equally to patients of both groups.
Ancillary study measuring metformin-induced enterohormones secretion will be performed on a subgroup of 30 patients randomized in this arm.
干预措施: Standard Care (Other)
Metformin + Standard care
The pharmacological treatment (Metformin) will start at dose of 850 mg once daily and, at one month, increased to 850 mg twice daily. The dosage will be adjusted if necessary because of gastrointestinal symptoms and information on dose change during follow-up will be collected Adherence to study medications will be assessed by pills count and plasmatic dosage (Metformin group).
All participants will receive standardized lifestyle recommendations regularly during all the time of the study Lifestyle recommendations will be provided by a nutritionist/diabetologist every 6 months at each study visit and reinforced by dedicated consultations with a dietician and a physical activity coach as usually performed in each center. This follow-up will be standardized for each center and applied equally to patients of both groups.
Ancillary study measuring metformin-induced enterohormones secretion will be performed on a subgroup of 30 patients randomized in this arm.
干预措施: Standardized meal (Dietary Supplement)
Standard Care
All participants will receive standardized lifestyle recommendations regularly during all the time of the study Lifestyle recommendations will be provided by a nutritionist/diabetologist every 6 months at each study visit and reinforced by dedicated consultations with a dietician and a physical activity coach as usually performed in each center. This follow-up will be standardized for each center and applied equally to patients of both groups.
Ancillary study measuring metformin-induced enterohormones secretion will be performed on a subgroup of 30 patients randomized in this arm.
干预措施: Standard Care (Other)
Standard Care
All participants will receive standardized lifestyle recommendations regularly during all the time of the study Lifestyle recommendations will be provided by a nutritionist/diabetologist every 6 months at each study visit and reinforced by dedicated consultations with a dietician and a physical activity coach as usually performed in each center. This follow-up will be standardized for each center and applied equally to patients of both groups.
Ancillary study measuring metformin-induced enterohormones secretion will be performed on a subgroup of 30 patients randomized in this arm.
干预措施: Standardized meal (Dietary Supplement)
结局指标
主要结局
Proportion of patients with partial or complete T2D remission criteria
时间窗: 3 years
* Complete remission: HbA1c\<5.7% and no anti-diabetic medications (except metformin in the experimental group). * Partial remission: defined as prediabetes level of glycaemia i.e. HbA1c\<6.5% and no anti-diabetic medications (except metformin in the experimental group).
次要结局
- Proportion of patients with strict complete T2D remission criteria(3 years)
- Percentage of weight and BMI change(1, 2 and 3 years)
- Level of blood calcium(1, 2 and 3 years)
- Level of blood vitamin D(1, 2 and 3 years)
- Proportion of adverse effects in the intervention group compared to standard care(3 years)
- Number of pills taken per patient(1, 2 and 3 years)
- Level of plasmatic metformin(1, 2 and 3 years)
- Proportion of retinopathy events(3 years)
- Proportion of nephropathy events(3 years)
- Proportion of macroangiopathy events(3 years)
- Numbers and proportions of patients with quality of life changes(1, 2 and 3 years)
- Proportion of patients with partial or complete T2D remission criteria(1 and 2 years)
- Level of blood iron(1, 2 and 3 years)
- Level of serum ferritin(1, 2 and 3 years)
- Level of blood vitamin B1(1, 2 and 3 years)
- Fasting glycemia(1, 2 and 3 years)
- Level of blood HDL cholesterol(1, 2 and 3 years)
- Transferrin saturation percentage(1, 2 and 3 years)
- Fasting insulinemia(1, 2 and 3 years)
- Level of blood triglycerides(1, 2 and 3 years)
- Level of blood albumin(1, 2 and 3 years)
- Blood pressure(1, 2 and 3 years)
- Level of blood hemoglobin(1, 2 and 3 years)
- Level of blood vitamin B9(1, 2 and 3 years)
- Level of blood vitamin B12(1, 2 and 3 years)
- Insulinemia(6 months or 12 months; under fasting condition then 30 and 90 min after a standardized meal)
- Level of glucagon(6 months or 12 months; under fasting condition then 30 and 90 min after a standardized meal)
- Clinical outcome at the end of the study(3 years)
- Changes in fecal microbiota(1 and 3 years)
- Glycemia(6 months or 12 months; under fasting condition then 30 and 90 min after a standardized meal)
- Level of GLP-1(6 months or 12 months; under fasting condition then 30 and 90 min after a standardized meal)
- Level of GLP-2(6 months or 12 months; under fasting condition then 30 and 90 min after a standardized meal)
- Level of GIP(6 months or 12 months; under fasting condition then 30 and 90 min after a standardized meal)
- Level of oxyntomodulin(6 months or 12 months; under fasting condition then 30 and 90 min after a standardized meal)
- Level of PYY(6 months or 12 months; under fasting condition then 30 and 90 min after a standardized meal)
- Level of ghrelin(6 months or 12 months; under fasting condition then 30 and 90 min after a standardized meal)
- Level of glicentin(6 months or 12 months; under fasting condition then 30 and 90 min after a standardized meal)