The results of this follow-up analysis show that 3 years after randomization, bariatric surgery, as compared with intensive medical therapy alone, was associated with superior and sustained glycemic control and weight reduction. Patients who underwent gastric bypass or sleeve gastrectomy were significantly more likely to achieve and maintain a glycated hemoglobin level of 6.0% or less than were those who received intensive medical therapy alone. More than one third of the patients in the gastric-bypass group and a fifth of those in the sleeve-gastrectomy group, as compared with no patients in the medical-therapy group, had a glycated hemoglobin level of 6.0% or less without the use of diabetes medications. Patients in the two surgical groups had a significant absolute decrease of 2.5 percentage points in glycated hemoglobin levels, a reduction that was sustained for 3 years, as compared with a reduction of 0.6 percentage points in the medical-therapy group. The results of surgery are particularly striking in this population with relatively long-standing uncontrolled disease. The surgically treated patients had superior glycemic control for 3 years while also reducing dependency on oral diabetes medications and insulin. More than 90% of surgical patients had glycemic control without the use of insulin. Weight loss and a shorter duration of diabetes were the main predictors of having a glycated hemoglobin level of 6.0% or less after surgery.

Analysis of secondary end points, including BMI, body weight, waist circumference, and levels of triglycerides and HDL cholesterol, also showed favorable results at 3 years in the surgical groups, as compared with the group receiving intensive medical therapy alone. Patients in the two surgical groups had a significant reduction in the use of antihypertensive and lipid-lowering agents, even though there were no significant changes from baseline measurements in blood pressure or LDL cholesterol among the three study groups. Some adverse effects of surgical treatment were observed in this study but were modest in severity and relatively uncommon after the first year.

Although observational studies have shown impressive improvements in glycemic control after bariatric surgery, with rates of improvement in diabetes ranging from 55 to 95%,1-5 direct comparisons with intensive medical therapy have been limited.6-10 The Swedish Obese Subjects (SOS) study, a nonrandomized, prospective trial comparing bariatric surgery with conventional medical treatment, showed higher rates of diabetes remission after surgery than after conventional medical treatment at 2, 10, and 20 years. The SOS study also showed significant reductions in long-term complications, including rates of death from any cause and major cardiovascular events, with surgical treatment.14-16

Five short-term, randomized, controlled trials compared bariatric surgery with medical treatment with respect to type 2 diabetes, with 1 to 2 years of follow-up.6-10 The initial STAMPEDE report showed that at 1 year, patients had better glycemic control (defined as a glycated hemoglobin level of 6.0% or less, with or without the use of medications) after gastric bypass (42% of patients) or sleeve gastrectomy (37%) than after intensive medical therapy (12%) (P<0.001 for both comparisons).7 All five trials showed that standard bariatric procedures, as compared with medical treatment alone, were associated with few major complications and resulted in superior glycemic control, weight reduction, and reductions in cardiovascular risk factors. Our findings show continued durability of glycemic control and persistent reductions in cardiovascular risk factors at 3 years after surgery. The diabetes remission rates after surgery in our study are similar to those reported by Ikramuddin et al.9 but are lower than those reported by Mingrone et al.8 Such discrepancies could be explained by the greater severity and longer duration of diabetes in our population, as well as a stricter definition of remission.

Observational studies have suggested that bariatric surgery may reduce long-term renal impairment associated with diabetes.4,17 Diabetes and obesity are independent risk factors for the development of albuminuria, which is associated with an increased risk of death from cardiovascular causes and end-stage renal disease.18 We noted improvement in albuminuria in the surgical groups despite a reduction in the use of renin–angiotensin system blockers, which suggests that bariatric surgery may have a role in the prevention of further renal parenchymal damage. Although there was no significant change in serum creatinine levels or the glomerular filtration rate, these findings do not imply a lack of benefit of weight loss on renal function, since creatinine and the glomerular filtration rate are influenced by loss of muscle mass associated with weight loss.19 Cumulatively, our data should be considered to be hypothesis-generating and suggest the need for further long-term studies examining the effects of bariatric surgery on renal function in diabetes.

Obese patients with diabetes have a reduced quality of life and ability to cope with associated chronic diseases. Using a validated quality-of-life instrument, we found significant improvements in five of eight mental and physical domains among patients in the gastric-bypass group and in two of eight domains among patients in the sleeve-gastrectomy group. Intensive medical therapy resulted in no significant improvements from baseline in quality of life.

Metabolic and weight-loss outcomes were generally similar in the two surgical groups at 1 year, although some advantages of gastric bypass over sleeve gastrectomy have emerged during longer follow-up, including a greater likelihood of reaching a glycated hemoglobin level of 7.0% or less (a therapeutic goal of the American Diabetes Association) with no use of diabetes medications, a reduced requirement for diabetes and cardiovascular medications, greater reductions in weight and BMI, and a greater improvement in quality of life. Some differences between the gastric-bypass group and the sleeve-gastrectomy group did not reach statistical significance, although the study was not adequately powered to detect modest differences between these procedures. In a prespecified substudy analysis of beta-cell function, insulin sensitivity, and body composition in a subgroup of patients, we found that at 2 years, gastric bypass was superior to sleeve gastrectomy with respect to insulin secretion, insulin sensitivity, and relative reduction in truncal fat as compared with subcutaneous fat.20

Most clinical guidelines and insurance coverage for bariatric surgery limit access to the surgery to patients with a BMI of 35 or more, presumably because of insufficient studies evaluating outcomes in patients with a BMI of less than 35. In our study, 49 of 137 patients (36%) had a BMI of 27 to 34, and these patients had an improvement in glycemic control and durability that was similar to that in patients with a BMI of 35 or more. Other trials and observational studies involving patients with only mild obesity showed similar improvements in glycemic control.21,22 Accordingly, some guidelines for diabetes management are beginning to endorse the use of bariatric surgery in patients with diabetes and a BMI of 30 to 34, especially those who have poor glycemic control despite receiving the best available medical therapy.23,24

Important limitations of our study include an inadequate sample size and duration to detect differences in the incidence of diabetes complications, such as myocardial infarction, stroke, or death. The protocol specifies further follow-up at 5 years for all patients, which should allow additional assessment of even longer-term efficacy and safety.

Despite these limitations, we conclude that bariatric surgery represents a potentially useful strategy for the management of type 2 diabetes, allowing many patients to reach and maintain therapeutic targets of glycemic control that otherwise would not be achievable with intensive medical therapy alone. Some patients in our study had complete diabetes remission, whereas others had a marked reduction in the need for pharmacologic treatment. The reduction in cardiovascular risk factors was sustained, allowing for reductions in lipid-lowering and antihypertensive therapies. Other benefits of surgery included a significant improvement in the quality of life. The question as to whether the documented benefits will reduce microvascular and macrovascular morbidity and mortality, as shown in nonrandomized studies, can be adequately answered only through larger, multicenter clinical-outcome trials.