In our study, obese patients with poorly controlled diabetes who underwent either gastric bypass or sleeve gastrectomy combined with medical therapy were significantly more likely to achieve a glycated hemoglobin level of 6.0% or less 12 months after randomization than were patients receiving medical therapy alone. Notably, many patients in the surgical groups, particularly those in the gastric-bypass group, achieved glycemic control without the use of diabetes medications (). The study population had relatively advanced disease, including many patients with major diabetes-related coexisting illnesses or evidence of end-organ damage, including retinopathy in 14 to 22% and nephropathy (microalbuminuria) in 14 to 29% (Table S1 in the Supplementary Appendix
). The majority of patients had the metabolic syndrome and increased measures of systemic inflammation (median high-sensitivity CRP level, >4 mg per liter) (, and Tables S1 and S2 in the Supplementary Appendix
). More than 60% of the surgical patients had moderate-to-severe fatty liver disease on the basis of biopsy samples obtained during surgery (Table S1 in the Supplementary Appendix
). Accordingly, a significant improvement in type 2 diabetes (a reduction in glycated hemoglobin levels of 2.9 percentage points) can occur after bariatric surgery in obese patients with advanced diabetes, although modest improvement is feasible with the use of intensive medical therapy alone (a reduction of 1.4 percentage points).
Observational studies of bariatric procedures have shown rates of remission of type 2 diabetes of 55 to 95%, although resolution was often determined without biochemical evidence (levels of glycated hemoglobin or fasting plasma glucose) or with the use of more liberal definitions of remission (e.g., fasting plasma glucose, ≤125 mg per deciliter [6.9 mmol per liter]).5
A nonrandomized, prospective trial comparing bariatric surgery with conventional treatment of obesity also showed higher diabetes remission rates for surgery after 2 and 10 years but with gradual recurrence over time.8
A single previous randomized, controlled trial compared medical therapy with gastric banding in patients with moderate-to-severe obesity (BMI, 30 to 40) but involved patients with early diabetes (<2 years) of mild severity (glycated hemoglobin, <7.5%). In that study, gastric banding was superior to medical therapy in achieving glycemic control (glycated hemoglobin, ≤6.2%) and weight loss.10
In contrast, in our trial, patients had more advanced type 2 diabetes, with an average disease duration of more than 8 years and a mean baseline glycated hemoglobin level of 8.9 to 9.5% while undergoing treatment with an average of nearly three diabetes agents, including a relatively high use of insulin (44% of patients) or other injectable therapies (14%). The inclusion of patients with more advanced type 2 diabetes in the STAMPEDE trial probably explains the lower observed rate of diabetes remission; other differences from previous trials included less severe obesity, a greater proportion of men and black patients, and an older age.
In our study, results were generally similar in the two surgical groups although somewhat more favorable in the gastric-bypass group. Most differences between the gastric-bypass group and the sleeve-gastrectomy group were not significant, although it should be noted that the study was not adequately powered to detect modest differences between these two surgical procedures. Secondary end points, including BMI, body weight, waist circumference, and the HOMA-IR index, also showed more favorable results in the surgical groups than in the medical-therapy group (, and Tables S2 and S3 in the Supplementary Appendix
). Maximal improvements after bariatric surgery occurred quickly, often within 3 months, and were maintained throughout the 12-month follow-up period. Reductions in the use of diabetes medications occurred before achievement of maximal weight loss, which supports the concept that the mechanisms of improvement in diabetes involve physiologic effects in addition to weight loss, probably related to alterations in gut hormones.17–20
As noted in observational studies, some adverse effects of surgical treatment were observed in this study but were modest in severity.6,7,9,21
Self-reported symptoms of hypoglycemia occurred with a similar frequency in the surgical and medical groups.
The mechanism of improved glycemic control appears to involve improvement in insulin sensitivity, with a marked reduction in insulin levels and improvement in the HOMA-IR index, which may be linked to the attenuation of chronic inflammation, as suggested by the greater reduction in high-sensitivity CRP in the surgery groups (−84% for gastric bypass and −80% for sleeve gastrectomy) than in the medical-therapy group (−33%). All patients received intensive medical therapy, including lifestyle counseling, home glucose monitoring, and the most effective pharmacotherapy currently available. Using these strategies, the patients receiving medical therapy alone did well, achieving a substantial reduction in glycated hemoglobin levels (−1.4 ± 1.5 percentage points, P<0.001) and body weight (−5.4 ± 8.0 kg, P<0.001) over 12 months. Although the study was not powered to assess the effects of improved glycemic control on clinical outcomes, improvements in cardiovascular risk factors were observed (, and Tables S2 and S3 in the Supplementary Appendix
). Although lipoprotein and blood-pressure levels were similar in all three study groups at 12 months, improvements in the surgical groups allowed reduction or elimination of concomitant medications in many patients.
Important limitations of our study include the relatively short duration of follow-up (12 months) and the single-center, open-label nature of the study. Some adverse events occurred in the bariatric-surgery group, including in four patients who required reoperation. The durability and long-term safety profile of these results remain uncertain, but the protocol specifies further 4-year follow-up of all patients, which should allow additional assessment of long-term efficacy and safety results to guide patient counseling regarding specific bariatric procedures for the treatment of type 2 diabetes.
Despite these limitations, we conclude that bariatric surgery represents a potentially useful strategy for management of uncontrolled diabetes, since it has been shown to eliminate the need for diabetes medications in some patients and to markedly reduce the need for drug treatment in others. In addition, among patients undergoing surgery, cardiovascular risk factors improved, allowing reductions in lipid-lowering and antihypertensive therapies. Theoretically, such improvements have the potential to reduce cardiovascular morbidity and mortality, as shown in nonrandomized studies, although such benefits will need to be balanced with surgical risk and safety as shown in larger, multicenter clinical-outcome trials.8,22