Elsevier

The Lancet

Volume 397, Issue 10271, 23–29 January 2021, Pages 293-304
The Lancet

Articles
Metabolic surgery versus conventional medical therapy in patients with type 2 diabetes: 10-year follow-up of an open-label, single-centre, randomised controlled trial

https://doi.org/10.1016/S0140-6736(20)32649-0Get rights and content

Summary

Background

No data from randomised controlled trials of metabolic surgery for diabetes are available beyond 5 years of follow-up. We aimed to assess 10-year follow-up after surgery compared with medical therapy for the treatment of type 2 diabetes.

Methods

We did a 10-year follow-up study of an open-label, single-centre (tertiary hospital in Rome, Italy), randomised controlled trial, in which patients with type 2 diabetes (baseline duration >5 years; glycated haemoglobin [HbA1c] >7·0%, and body-mass index ≥35 kg/m2) were randomly assigned (1:1:1) to medical therapy, Roux-en-Y gastric bypass (RYGB), or biliopancreatic diversion (BPD) by a computerised system. The primary endpoint of the study was diabetes remission at 2 years (HbA1c <6·5% and fasting glycaemia <5·55 mmol/L without ongoing medication for at least 1 year). In the 10-year analysis, durability of diabetes remission was analysed by intention to treat (ITT). This study is registered with ClinicalTrials.gov, NCT00888836.

Findings

Between April 30, 2009, and Oct 31, 2011, of 72 patients assessed for eligibility, 60 were included. The 10-year follow-up rate was 95·0% (57 of 60). Of all patients who were surgically treated, 15 (37·5%) maintained diabetes remission throughout the 10-year period. Specifically, 10-year remission rates in the ITT population were 5·5% for medical therapy (95% CI 1·0–25·7; one participant went into remission after crossover to surgery), 50·0% for BPD (29·9–70·1), and 25·0% for RYGB (11·2–46·9; p=0·0082). 20 (58·8%) of 34 participants who were observed to be in remission at 2 years had a relapse of hyperglycaemia during the follow-up period (BPD 52·6% [95% CI 31·7–72·7]; RYGB 66·7% [41·7–84·8]). All individuals with relapse, however, maintained adequate glycaemic control at 10 years (mean HbA1c 6·7% [SD 0·2]). Participants in the RYGB and BPD groups had fewer diabetes-related complications than those in the medical therapy group (relative risk 0·07 [95% CI 0·01–0·48] for both comparisons). Serious adverse events occurred more frequently among participants in the BPD group (odds ratio [OR] for BPD vs medical therapy 2·7 [95% CI 1·3–5·6]; OR for RYGB vs medical therapy 0·7 [0·3–1·9]).

Interpretation

Metabolic surgery is more effective than conventional medical therapy in the long-term control of type 2 diabetes. Clinicians and policy makers should ensure that metabolic surgery is appropriately considered in the management of patients with obesity and type 2 diabetes.

Funding

Fondazione Policlinico Universitario Agostino Gemelli IRCCS.

Introduction

A large body of evidence accumulated over the past two decades has led to the repurposing of bariatric surgery as a treatment for type 2 diabetes, a practice referred to as metabolic surgery.1, 2 Several randomised controlled trials2, 3, 4, 5, 6, 7 comparing surgery and conventional medical therapy specifically for the treatment of type 2 diabetes show that metabolic surgery results in major short-term to mid-term improvements in hyperglycaemia, prolonged disease remission, reduced cardiometabolic risk, reduced hypertension,8 and lower incidence of chronic kidney disease.9

The ability of metabolic surgery to induce prolonged remission of diabetes, defined as non-diabetic glycaemia without the need for ongoing pharmacological treatment,10 makes surgery a potentially curative approach to type 2 diabetes.11 In 2009, a consensus statement by the American Diabetes Association operationally defined cure of type 2 diabetes as the maintenance of stable remission of hyperglycaemia for at least 5 years.10

Although observational studies of traditional bariatric surgery suggest that diabetes remission can persist long term,12, 13 it is difficult to extrapolate these findings to the broader population of patients with type 2 diabetes. Patients seeking traditional bariatric surgery are typically younger, and have a shorter duration of diabetes and lower prevalence of insulin dependency and cardiovascular disease at baseline when compared with patients who seek metabolic surgery specifically to treat type 2 diabetes.14 Since duration of diabetes and insulin use are inversely associated with diabetes remission and positively associated with diabetes relapse,15, 16, 17 observational studies of traditional bariatric surgery might overestimate durability of diabetes remission and other benefits of surgery in patients with type 2 diabetes.

Research in context

Evidence before this study

We searched MEDLINE from Jan 1, 2000, to Nov 30, 2020, for randomised clinical trials, case-control studies, and observational series reporting on diabetes remission or comparisons of medical and surgical treatment for type 2 diabetes. Keywords included “bariatric surgery”, “metabolic surgery”, “type 2 diabetes”, “remission”, and “very-low-calorie diet”. Observational studies of traditional bariatric surgery suggest that surgically induced remission of type 2 diabetes can persist long term. However, such studies might overestimate durability of disease remission and other benefits of surgery in type 2 diabetes given that the vast majority of patients seeking bariatric surgery are typically younger and have early or milder disease than the broader population of people with type 2 diabetes. To our knowledge, there are no data from randomised controlled trials specifically comparing metabolic surgery and conventional diabetes therapy in patients with advanced type 2 diabetes, beyond 5 years of follow-up.

Added value of this study

Here, we report for the first time to our knowledge, the 10-year outcomes of a randomised controlled trial comparing surgery with medical therapy plus lifestyle interventions for type 2 diabetes. Surgery induced continued 10-year remission of diabetes—defined as non-diabetic glycaemia (glycated haemoglobin <6·5%) without the need for ongoing pharmacological treatment—in 37% of patients with advanced type 2 diabetes at baseline. Compared with medical therapy, surgery was associated with greater weight loss, reduced medication use, lower cardiovascular risk, better quality of life, and a lower incidence of diabetes-related complications.

Implications of all the available evidence

These data show that type 2 diabetes is a potentially curable disease. Metabolic surgery is more effective than medical therapy in the long-term control of advanced type 2 diabetes. Clinicians and policy makers should ensure that metabolic surgery is appropriately considered in the management of patients with obesity and type 2 diabetes.

To date, there are no data beyond 5 years from randomised controlled trials specifically designed to investigate the efficacy of metabolic surgery for type 2 diabetes.3, 4, 5 We aimed to report the 10-year outcomes of our randomised controlled trial to compare metabolic surgery by Roux-en-Y gastric bypass (RYGB) and biliopancreatic diversion (BPD) with medical therapy plus lifestyle interventions for the treatment of advanced type 2 diabetes. The 2-year3 and 5-year18 outcomes of the study were previously reported and we continued to follow up patients for evaluation of durability of diabetes remission and secondary endpoints.

Section snippets

Study design and participants

Briefly, we did a 10-year follow-up of a three-group, open-label, single-centre (tertiary hospital in Rome, Italy), randomised controlled trial comparing metabolic surgery, by either RYGB or BPD, with conventional medical therapy plus lifestyle interventions for type 2 diabetes. Participants were included if they were aged 30–60 years, had a body-mass index (BMI) of 35 kg/m2 or greater, a history of type 2 diabetes lasting at least 5 years, and a glycated haemoglobin (HbA1c) concentration of

Results

Between April 30, 2009, and Oct 31, 2011, of 72 patients assessed for eligibility, 60 were randomly assigned to the conventional medical therapy (n=20), RYGB (n=20), or BPD (n=20) groups. Demographic data at baseline are reported in table 1.

In the medical therapy group, two patients were lost to follow up shortly after random assignment, one patient died of myocardial infarction, and two crossed over to metabolic surgery after completion of the assessment for the primary endpoint (2 years after

Discussion

The results of our study showed that metabolic surgery is more effective than medical and lifestyle interventions in the long-term control of type 2 diabetes. Surgery resulted in durable remission of type 2 diabetes, with more than a third of patients maintaining non-diabetic concentrations of glycaemia without the need for diabetes medications for the entire 10-year study period. Compared with medical therapy, surgery also resulted in a significantly greater reduction in HbA1c concentrations

Data sharing

Anonymised patient data are available for use in collaborative studies to researchers upon reasonable request to the corresponding author ([email protected]). Data will be provided following the review and approval of a research proposal (including a statistical analysis plan) and completion of a data sharing agreement. Responses to the request for the raw data will be judged by a committee including GM, SP, and FR.

References (30)

  • PR Schauer et al.

    Clinical outcomes of metabolic surgery: efficacy of glycemic control, weight loss, and remission of diabetes

    Diabetes Care

    (2016)
  • CA Schiavon et al.

    Effects of bariatric surgery in obese patients with hypertension: the GATEWAY randomized trial (Gastric Bypass to Treat Obese Patients With Steady Hypertension)

    Circulation

    (2018)
  • RV Cohen et al.

    Effect of gastric bypass vs best medical treatment on early-stage chronic kidney disease in patients with type 2 diabetes and obesity: a randomized clinical trial

    JAMA Surg

    (2020)
  • JB Buse et al.

    How do we define cure of diabetes?

    Diabetes Care

    (2009)
  • F Rubino et al.

    Potential of surgery for curing type 2 diabetes mellitus

    Ann Surg

    (2002)
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