Extending Time Without Diabetes After Bariatric Surgery: a Trial Comparing the Metformin Addition or Not to Standard Care — DiabOUT  

Diabetes Clinical Trial

Official title: Extending Time Without Diabetes After Bariatric Surgery: a Randomized Controlled Trial Comparing the Metformin Addition or Not to Standard Care

Status Recruiting

Clinical Trial Summary

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.

Clinical Trial Description

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:

• Standardized care plus metformin treatment if randomized in the experimental group given for 3 years

• Standardized care alone if randomized in the reference group

Primary objective is to demonstrate that metformin increases the proportion of patients with T2D remission compared to standard care among ex-T2D patients operated of BS, after a 3-year period of treatment.

Secondary objectives are:

• To assess the proportion of patients with T2D partial or complete remission with metformin compared to standard care in ex-T2D patients operated of BS, after 1 and 2 years of treatment.

• To assess body weight and metabolic parameters in metformin group versus standard care.

• To assess tolerance, nutritional status and adherence to metformin in intervention group versus standard care.

• To assess micro and macroangiopathy at 3 years.

• To assess quality of life changes from baseline at 1, 2 and 3 years.

• To assess the accuracy of long term prediction score (i.e. prolonged remission assessed at the end of the study with the Ad-DiaRem score)

• To explore gut contribution to metformin metabolic effect by: (i) gut microbiota differences (diversity, composition and function) between metformin treated and non-treated individuals and (ii) measurements of metformin-induced enterohormones secretion

Patients are followed up every 6 months during 3 years in both arms. If diabetes is diagnosed during the follow-up (HbA1c > 6.5 %), the primary endpoint of the study is obtained meaning end of diabetes remission but patients will be still followed up to the end of protocol to monitor the secondary endpoints. When remission is over, the care defined by the protocol (ie metformin + standardized care or standardized care alone) should be stopped. In both groups, when remission is over, management of the disease has to be adapted according to physician's and patient's preference whatever the arm of randomization. ;

Related Conditions & MeSH terms

• Bariatric Surgery
• Diabetes
• Diabetes Mellitus
• Metformin

• NCT number: NCT04581447
• Study type: Interventional
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: Aurélie GUIMFACK
• Email: aurelie.guimfack@aphp.fr
• Status: Recruiting
• Phase: Phase 3
• Start date: January 7, 2021
• Completion date: November 2026