Study Overview
Objective. To examine the 3-year efficacy of bariatric surgery on resolution of diabetes.
Design. Randomized controlled trial.
Setting and participants. Patients were participants in the STAMPEDE trial, a single-center study with enrollment from March 2007 to January 2011. 150 patients aged 20 to 60 years with a hemoglobin A1cof > 7% and a BMI of 27 to 43 kg/m 2 were studied. Patients were excluded for a history of bariatric surgery or complex abdominal surgery and poorly controlled medical or psychiatric conditions [1]. Patients were randomized to intensive medical therapy, Roux-en-Y gastric bypass, or sleeve gastrectomy. All participants received intensive medical therapy, including lifestyle education, diabetes medical management, and cardiovascular risk reduction administered by a diabetes specialist every 3 months for 2 years and every 6 months thereafter. All surgeries were performed by a single surgeon, using equipment by Ethicon (a sponsor of the study, along with the National Institutes of Health, LifeScan, and the Cleveland Clinic).
Main outcome measure. HbA1c of ≤ 6% at 3 years.
Main results . At baseline, 68% were women and 74% were white. Participants had a mean age of 48 years (SD 8), mean A1c of 9.3% (1.5%), and mean BMI of 36 (3.5). 43% required insulin at baseline. Follow-up at 3 years was 91% (9 participants dropped out after enrollment, 4 lost to follow-up), and at this time, A1c levels were ≤ 6% for 5% of intensive medical therapy participants, 38% who had gastric bypass (P < 0.001 compared with medical therapy), and 24% who had sleeve gastrectomy (P = 0.01 compared with medical therapy); the difference between bypass and sleeve gastrectomy arms was not significant (P = 0.17). Nearly all of the participants reaching the primary outcome in the bariatric surgery arms achieved this goal A1c without using diabetic medications (35% and 20%). For the secondary outcome of A1c ≤ 7% without using diabetic medications, 0%, 58%, and 33% reached this endpoint in the medical therapy, bypass, and sleeve gastrectomy arms, respectively (P < 0.001 for both surgery arms compared to medical therapy; P = 0.01 comparing gastric bypass to sleeve gastrectomy). At 3 years, 2%, 69%, and 43% of participants were not taking any diabetic medications; 55% of medical therapy participants were taking insulin compared with 6% and 8% in the surgery arms. Weight loss was significantly greater in the gastric bypass and sleeve gastrectomy arms (24.5% and 21.1% of baseline body weight compared with the medical therapy arm with 4.2%). HDL cholesterol was higher and triglycerides were lower in both surgery arms, compared with medical therapy, but LDL cholesterol and blood pressure were not significantly different. Surgery participants also were taking fewer cardiovascular medications at 3 years. Quality of life was improved in 5 of 8 domains for the bypass arm compared with medical therapy and in 3 of 8 domains for the sleeve gastrectomy arm.
Conclusion. Gastric bypass and sleeve gastrectomy surgery leads to substantial resolution of diabetes compared to medical therapy.
Commentary
Over the last several decades, bariatric surgery has emerged as important treatment for obesity. Observational studies have demonstrated sustained weight loss persisting up to 15 years, as well as reductions in cardiovascular risk, diabetes, and even mortality [2–5]. In the Swedish Obesity Study, a nonrandomized study of 2010 participants undergoing bariatric surgery and 2037 matched controls, gastric bypass led to a 32% reduction from baseline body weight at 1–2 years after surgery with sustained weight loss of 27% at 15 years [2,3]. Patients undergoing gastric banding lost a bit less weight, with 20% weight loss at 1–2 years and 13% at 15 years. Control subjects lost very little.
Among diabetic Swedish Obesity Study participants, bariatric surgery led to a much higher rate of remission from diabetes over 10 years compared with control patients (36% after surgery, 13% among controls) [2] and lower rates of microvascular and macrovascular complications [6]. Among participants who were not diabetic at baseline, the incidence of diabetes was just 7% in the surgery arm and 24% in the control arm [2]; this difference in incidence persisted for 15 years of follow-up [4].
Among randomized controlled trials, several studies have found short-term resolution of diabetes after surgery. A study of 60 patients (age 30 to 60 years, BMI ≥ 35, A1c ≥ 7%) found that 75% of patients undergoing gastric bypass and 95% of patients undergoing biliopancreatic diversion had fasting glucose of < 100 mg/dL and A1c < 6.5% at 2 years; none of the control subjects met these thresholds for diabetes resolution [7]. Another 1-year trial of 120 US and Taiwanese patients (age 30 to 67 years, BMI 30 to 39.9, A1c ≥ 8%) found that 48% randomized to gastric bypass met a combination endpoint of A1c < 7%, LDL cholesterol < 100 mg/dL, and systolic blood pressure of < 130 mm Hg after 1 year compared with 19% assigned to intensive medical therapy [8]. In the gastric bypass arm, 75% reached an A1c of < 7% compared with 32% receiving medical therapy.
What does the study by Schauer and colleagues contribute? First, the study extended data on diabetes resolution to 3 years, longer than prior studies, and found substantial diabetes resolution in more than 1/3 of gastric bypass patients and 1/4 of sleeve gastrectomy patients (5% receiving medical therapy); over 2/3 and 1/3, respectively, were no longer taking any diabetes medications compared with 2% receiving medical therapy. In an earlier published study reporting on 1-year outcomes of this study, Schauer found diabetes resolution in 42% of those undergoing gastric bypass, 37% with sleeve gastrectomy, and 12% with medical therapy, demonstrating some regression over time [1]. Second, the study compared patients undergoing gastric bypass and sleeve gastrectomy. Sleeve gastrectomy is a newer procedure with less long-term outcome data; for example, none of the Swedish Obesity Study participants had sleeve gastrectomy. Schauer et al demonstrated that both procedures provide similar results for the primary outcome, but use of glucose-lowering medications was less and weight loss was more in the gastric bypass arm. These results provide some evidence that bypass surgery might be superior. Third, the study provided important data on cardiovascular risk factors, showing improvement in triglycerides and HDL cholesterol and quality of life. Quality of life was better after surgery than with medical therapy.
In this study, only 4 patients required reoperations, and no deaths or life-threatening complications were reported. However, mortality and morbidity remain a concern in bariatric surgery. In the earlier published study of this trial, authors noted that 22% of gastric bypass required hospitalization in the year after surgery compared with 8% in the sleeve gastrectomy and 9% in the medical therapy arms [1]. Observational data has shown higher rates of complications. In a study of patients at 10 clinical sites across the US from 2005 to 2007, 30-day mortality was 2.1% for open Roux-en Y gastric bypass and 0.2% for laparoscopic bypass [9]. That study also found substantial morbidity, with nearly 8% of patients after open bypass surgery reaching a composite end-point of death, deep venous thromboembolism, a repeat operation, or persistent hospitalization for 30 days after surgery; 4.8% reached this composite outcome after laparoscopic bypass. In another study of Medicare patients, 30-day mortality was 4.8% after open gastric bypass surgery compared with 1.7% for younger patients [10].
This trial by Schauer and colleagues demonstrates important benefits of gastric bypass and sleeve gastrectomy. While bariatric surgery still has some risk, it increasingly appears to be a viable treatment for patients with obesity, especially if they also have diabetes. Ideal future studies would be large enough to provide more data on predictors of diabetes resolution and long-term successful weight loss. Such information would allow clinicians and patients to better predict how patients might respond to surgery over the long term.
Applications for Clinical Practice
Bariatric surgery leads to a substantial reduction in diabetes over 3 years. While reduction was similar after gastric bypass and sleeve gastrectomy, secondary endpoints demonstrate some superiority of gastric bypass surgery. Clinicians should feel increasingly confident recommending bariatric surgery for their patients with diabetes and obesity.
—Jason P. Block, MD, MPH