Surgery for Weight Loss or Health Gain?

Although bariatric surgery was initially conceived as a means of treating obesity with the primary goal of weight reduction, the recognition of the rapid improvements in glycemic control in patients with type 2 diabetes (T2D) prompted clinicians to reconsider the benefits and indications for surgery. Subsequent mechanistic studies supported the powerful physiological changes following bariatric surgery, which could induce diabetes remission through weight loss–dependent and –independent pathways. As such, the concept of metabolic surgery was developed, with gastrointestinal surgery posited as a highly effective treatment for patients with obesity and T2D, shifting the focus from weight loss to glycemic control (1). Given the potential benefit of achieving improved glycemic control, metabolic surgery has been endorsed by the American Diabetes Association (ADA) and other international bodies for patients at a lower BMI threshold who would be considered to have only moderate obesity (2). In spite of the development of numerous new drug classes for the treatment of T2D, achieving good control as prescribed by the ADA guidelines has remained challenging, with only 23% of patients treated medically reaching the target for HbA_1c, blood pressure, and lipids (3). Given the continued limitations of pharmacological treatment for T2D, the possibility of using a surgical approach, which not only could improve glycemic control but may actually induce remission, was seen as a remarkable advance. Early enthusiasm for bariatric surgery as a cure for diabetes has been replaced by a more realistic view that it is highly effective for inducing remission in light of longer-term evidence that would suggest that a proportion of patients will experience a relapse of diabetes. In spite of this, it is worth considering data from the only randomized controlled trial (RCT) with 10-year follow-up data demonstrating that glycemic control following surgery remains better compared with control after medical therapy, even in patients who experience relapse of diabetes (4,5).

There is now a substantial body of evidence from RCTs that supports the superiority of bariatric surgery over medical therapy as a means of improving glycemia in patients with obesity and T2D. In spite of this, there are limitations to what can be drawn from these studies, as they have comparatively small sample sizes and tend to lack long-term follow-up (>10 years) data. In this issue of Diabetes Care, Kirwan et al. (6) provide an important contribution to strengthening the quality of evidence available to support the efficacy of metabolic surgery in individuals with obesity and T2D. In the Alliance of Randomized Trials of Medicine versus Metabolic Surgery in Type 2 Diabetes (ARMMS-T2D), the investigators have undertaken a prospective observational study of patients with T2D and class I–III obesity who had previously been randomized to undergo either metabolic surgery or medical/lifestyle management. The patients were drawn from four separate high-quality RCTs (Surgical Treatment and Medications Potentially Eradicate Diabetes Efficiently [STAMPEDE] trial, Calorie Reduction Or Surgery: Seeking to Reduce Obesity And Diabetes Study [CROSSROADS], Surgery or Lifestyle with Intensive Medical Management in Treatment of Type 2 Diabetes [SLIMM-T2D] trial, and Randomized Trial to Compare Surgical and Medical Treatments for Type 2 Diabetes [TRIABETES]) and had previously been randomized to medical or surgical therapy (7–9). The primary endpoint was the rate of diabetes remission at 3 years as defined by the ADA criteria (HbA_1c <6.5% with the patient off all glucose-lowering agents for 3 months). Secondary endpoints included long-term diabetes control, body weight, waist circumference, number of glucose-lowering agents used, and safety. A total of 316 patients who had previously been randomized to either surgery or medical therapy were included in the final analysis. At the trial conclusion at 3 years, there was a greater number of patients in the surgical group who reached the primary endpoint of diabetes remission compared with those treated medically, 37.5% vs. 2.6%, respectively (P < 0.001). The probability of achieving remission was 41.6% (95% CI 29.6–58.3%) following surgery compared with 1% (95% CI 0.2–4%) for the group of patients treated medically (P < 0.001). There was also a significant reduction in the number of medications required for the treatment of diabetes, hypertension, and dyslipidemia.

This study adds further support to the principle of using surgical approaches to the treatment of T2D in patients with obesity in providing data from the largest cohort of patients prospectively randomized to either surgical or medical treatment. Irrespective of the procedure performed, including gastric band, patients were more likely to have a clinically significant reduction in HbA_1c than those treated with medical therapy with higher rates of diabetes remission at 3 years. Critically, this also provides additional evidence to support the efficacy and safety of metabolic surgery in patients with class I obesity, a group often overlooked for considering surgery. The reductions in cardiovascular risk factors including hypertension and dyslipidemia as well as glycemia, well-recognized contributors to the development of macrovascular disease, following surgery compared with medicine are also noteworthy, as achieving adequate control has posed an ongoing challenge in the delivery of medically led diabetes care. There are limitations of the study that should be acknowledged including the differences between the two arms at baseline, particularly regarding insulin use, as well as the fact that novel agents such as glucagon-like peptide 1 analogs and sodium–glucose cotransporter 2 inhibitor drugs were not routinely used. Additionally, the study was not powered to detect differences in outcomes between different surgical procedures.

In spite of mounting evidence from RCTs demonstrating the efficacy of bariatric surgery as a treatment for T2D in patients with obesity, studies to date have been limited by relatively small sample sizes and short length of follow-up. Critically, this study provides prospective data on the largest cohort of patients, which support a higher likelihood of not only diabetes remission but also a reduction in cardiovascular risk factors with surgery compared with medical therapy. Unfortunately, even with the enhanced power of combining several RCTs, the resultant data remain insufficient to answer the question of whether bariatric surgery will prevent cardiovascular events. For this, a new definitive study is required. Given the promising new development of several novel classes of drugs for obesity and diabetes that reduce cardiovascular events, it would be most interesting to examine whether surgery not only can produce more weight loss but also can result in enhanced health gain in patients with diabetes and obesity (10).

The treatment of T2D with multiple pharmacological agents, targeting different elements of the disease process, proved to be a major change in how patients are managed. The medical management of patients today continues to reflect this approach, and critically it has been demonstrated to result in reductions in mortality (11). Although medical management alone has since been demonstrated to be less effective than surgery in improving glycemic control and other cardiovascular risk factors, the principle of combining different modalities remains valid. Rather than asking the question of whether surgery is better than medications, perhaps we should be asking whether extending the concept of multimodal care, combining medications with surgery, can improve the treatment of T2D in patients with obesity.