Elsevier

The Lancet

Volume 386, Issue 9997, 5–11 September 2015, Pages 964-973
The Lancet

Articles
Bariatric–metabolic surgery versus conventional medical treatment in obese patients with type 2 diabetes: 5 year follow-up of an open-label, single-centre, randomised controlled trial

https://doi.org/10.1016/S0140-6736(15)00075-6Get rights and content

Summary

Background

Randomised controlled trials have shown that bariatric surgery is more effective than conventional treatment for the short-term control of type-2 diabetes. However, published studies are characterised by a relatively short follow-up. We aimed to assess 5 year outcomes from our randomised trial designed to compare surgery with conventional medical treatment for the treatment of type 2 diabetes in obese patients.

Methods

We did our open-label, randomised controlled trial at one diabetes centre in Italy. Patients aged 30–60 years with a body-mass index of 35 kg/m2 or more and a history of type 2 diabetes lasting at least 5 years were randomly assigned (1:1:1), via a computer-generated randomisation procedure, to receive either medical treatment or surgery by Roux-en-Y gastric bypass or biliopancreatic diversion. Participants were aware of treatment allocation before the operation and study investigators were aware from the point of randomisation. The primary endpoint was the rate of diabetes remission at 2 years, defined as a glycated haemaglobin A1c (HbA1c) concentration of 6·5% or less (≤47·5 mmol/mol) and a fasting glucose concentration of 5·6 mmol/L or less without active pharmacological treatment for 1 year. Here we analyse glycaemic and metabolic control, cardiovascular risk, medication use, quality of life, and long-term complications 5 years after randomisation. Analysis was by intention to treat for the primary endpoint and by per protocol for the 5 year follow-up. This study is registered with ClinicalTrials.gov, number NCT00888836.

Findings

Between April 27, 2009, and Oct 31, 2009, we randomly assigned 60 patients to receive either medical treatment (n=20) or surgery by gastric bypass (n=20) or biliopancreatic diversion (n=20); 53 (88%) patients completed 5 years' follow-up. Overall, 19 (50%) of the 38 surgical patients (seven [37%] of 19 in the gastric bypass group and 12 [63%] of 19 in the bilipancreatic diversion group) maintained diabetes remission at 5 years, compared with none of the 15 medically treated patients (p=0·0007). We recorded relapse of hyperglycaemia in eight (53%) of the 15 patients who achieved 2 year remission in the gastric bypass group and seven (37%) of the 19 patients who achieved 2 year remission in the biliopancreatic diversion group. Eight (42%) patients who underwent gastric bypass and 13 (68%) patients who underwent biliopancreatic diversion had an HbA1c concentration of 6·5% or less (≤47·5 mmol/mol) with or without medication, compared with four (27%) medically treated patients (p=0·0457). Surgical patients lost more weight than medically treated patients, but weight changes did not predict diabetes remission or relapse after surgery. Both surgical procedures were associated with significantly lower plasma lipids, cardiovascular risk, and medication use. Five major complications of diabetes (including one fatal myocardial infarction) arose in four (27%) patients in the medical group compared with only one complication in the gastric bypass group and no complications in the biliopancreatic diversion group. No late complications or deaths occurred in the surgery groups. Nutritional side-effects were noted mainly after biliopancreatic diversion.

Interpretation

Surgery is more effective than medical treatment for the long-term control of obese patients with type 2 diabetes and should be considered in the treatment algorithm of this disease. However, continued monitoring of glycaemic control is warranted because of potential relapse of hyperglycaemia.

Funding

Catholic University of Rome.

Introduction

Bariatric surgery is emerging as a valuable treatment option for patients with type 2 diabetes. The rationale for this concept is based on the substantial clinical improvement of type 2 diabetes after bariatric surgery,1 and on the growing body of evidence that gastrointestinal operations can directly affect glucose metabolism, independently of weight loss.2, 3

Intensive lifestyle modification strategies can improve glycaemic and metabolic control in patients with type 2 diabetes, but they do not reduce cardiovascular risk and mortality compared with standard diabetes treatment. 4 By contrast, long-term case-control studies show that, compared with usual care, bariatric surgery can lead to major reductions in hyperglycaemia or to diabetes remission, and can reduce cardiovascular disease and death,4, 5, 6, 7 especially in patients with type 2 diabetes.

Research in context

Evidence before this study

We searched MEDLINE, Embase, and The Cochrane Library between Jan 1, 2015, and May 15, 2015, for randomised controlled trials comparing bariatric surgery with medical treatment for type 2 diabetes. Our search terms were “bariatric surgery”, “diabetes”, “remission”, “Roux-en-Y gastric bypass” and “bilio-pancreatic diversion”. Randomised trials were included for evidence of glycaemic outcomes; long-term case-control studies were also used to assess evidence of cardiovascular risk and cardiovascular disease reduction after bariatric or metabolic surgery. Only randomised trials with previously published protocols in official sites were considered. Findings from previous trials have shown that bariatric surgery is more effective than conventional treatments for the short-term control of type 2 diabetes. Case-control studies suggest that bariatric surgery might reduce cardiovascular risk and mortality in obese patients with type 2 diabetes.

Added value of this study

Published randomised controlled trials are characterised by a relatively short follow-up time (1–3 years). This is the first report of 5 year outcomes from a trial designed to compare surgery with medical treatment specifically for the treatment of type 2 diabetes. Our findings show that bariatric surgery is more effective than medical treatment for the long-term control of obese patients with type 2 diabetes. Compared with medical treatment, surgery resulted in sustained remission of diabetes in a significant number of patients and in a greater reduction of cardiovascular risk, diabetes-related complications, and medication use, including use of insulin and cardiovascular drugs. Up to 50% of patients who had initial diabetes remission had a relapse of mild hyperglycaemia 5 years after surgery. However, more than 80% of surgically treated patients maintained the American Diabetes Association treatment goal of a glycated haemoglobin A1c concentration less than 7·0% (<53 mmol/mol), despite little or no need for antidiabetic drugs.

Implications of all the available evidence

The available evidence supports consideration of surgery in the treatment algorithm of type 2 diabetes. The ability of surgery to greatly reduce use of diabetes and cardiovascular drugs suggests that surgical treatment of diabetes is a cost-efficient therapeutic approach for this disease. The results of our study also add to a growing body of evidence showing that the gastrointestinal tract is a rational biological target for antidiabetic interventions and support further research into the mechanisms of action of surgery as a way to identify new, less invasive approaches of curative intent.

Several short-term to medium-term (1–3 year) randomised controlled trials comparing bariatric surgery with conventional diabetes management have shown that various surgical procedures, including Roux-en-Y gastric bypass, sleeve gastrectomy, biliopancreatic diversion, and gastric banding, improve type 2 diabetes more effectively than do drugs and lifestyle interventions.8, 9, 10, 11, 12, 13 In one of these trials,10 our group compared biliopancreatic diversion and Roux-en-Y gastric bypass with standard medical treatment in patients with severe obesity and diabetes (body-mass index [BMI] >35 kg/m2). As many as 95% of patients who underwent biliopancreatic diversion, and 75% of those who underwent Roux-en-Y gastric bypass, achieved the primary endpoint of diabetes remission at 2 years, compared with none of the patients in the medical treatment group. Despite these findings, published trials, including our previous study, are characterised by a relatively short follow-up time (1–3 years).

Here we present the 5 year follow-up data from our randomised controlled trial.10 We assessed durability of diabetes remission, overall glycaemic and metabolic control, cardiovascular risk, medication use, quality of life, diabetes-related complications, and long-term surgical complications.

Section snippets

Study design and patients

The study design and methods have been previously described.10 Briefly, we did a three-group, open-label, randomised controlled trial at the Catholic University diabetes centre in Rome, Italy. Inclusion criteria were an age of 30–60 years, a BMI of 35 kg/m2 or more, a history of type 2 diabetes lasting at least 5 years, glycated haemoglobin A1c (HbA1c) concentration of ≥7·0% or more (≥53 mmol/mol), and ability to understand and comply with the study protocol. Exclusion criteria were a history

Results

Figure 1 shows the trial profile. Between April 27, 2009, and Oct 31, 2009, we randomly assigned 60 patients to receive either medical treatment (n=20) or surgery by gastric bypass (n=20) or biliopancreatic diversion (n=20); 53 (88%) patients completed 5 years' follow-up (figure 1). After completion of the 2 year analysis, two (3%) patients in the medical treatment group crossed over to surgery due to inadequate glycaemic control: one patient underwent gastric bypass at month 30 after

Discussion

Roux-en-Y gastric bypass and biliopancreatic diversion were both more effective than standard medical treatment for the long-term control of hyperglycaemia and for patients' overall metabolic profile. Surgery also resulted in a greater reduction of cardiovascular risk, diabetes-related complications, and medication use, including glucose-lowering drugs, insulin, and cardiovascular drugs. Furthermore, surgical patients had a better quality of life than medically treated patients. The medical

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