February 15, 2017

expert reaction to study looking at bariatric surgery versus medical therapy for type 2 diabetes

Published in the New England Journal of Medicine the five-year outcome of randomised, controlled trials showed that, among patients with type 2 diabetes and a BMI of 27 to 43, bariatric surgery plus intensive medical therapy was more effective than intensive medical therapy alone in decreasing – or in some cases resolving – hyperglycemia.

Prof. Nick Finer, Consultant Endocrinologist and Bariatric Physician, UCL, and Society for Endocrinology member said:

“This data from a randomised trial comparing bariatric surgery with ‘best’ medical therapy for people with diabetes shows that 5 years after weight loss surgery, overweight and obese people with diabetes had better control of their diabetes, were on fewer drugs and had a better quality of life than those treated with conventional medical treatment.  These findings reinforce recent NICE recommendations that people with type 2 diabetes should be considered for and offered bariatric surgery.

“This is a high-quality study applying the rigour of a randomised trial to either medical therapy (which was successful at producing modest weight loss and initially improved blood glucose control) versus one of two bariatric surgical operations (sleeve gastrectomy – now the commonest operation in England; or gastric bypass – long considered the ‘gold standard’ procedure).  These are excellent results and good news for people with diabetes but slightly tempered compared to some claims for surgery.  Thus, at 5 years only 45% of people receiving gastric bypass and 25% sleeve gastrectomy were off all anti-diabetes medications.

“The lowest weight after surgery was achieved at around 18 months, with small and gradual weight regain thereafter, although even after 5 years patients were 19-23 kg lighter than before treatment, compared to about 5 kg for those on medical therapy.  Furthermore, the use of newer diabetes medications that can also produce weight loss, and weight loss drugs themselves was low, so it is possible that the medical group could (if more intensively treated) do even better.

“The study did not have sufficient power to determine which of the two operations was the better, although gastric bypass produced more weight loss and a slightly better chance of patients being able to stop diabetes medications.  This study accentuates the need for the NHS to expand the provision of bariatric surgery – sadly the numbers being treated in England have been steadily falling due to rationing.”

Prof. Naveed Sattar, Professor of Metabolic Medicine, University of Glasgow, said:

“This five year trial, which was generally well done, of bariatric surgery on top of intensive medical therapy in patients with longstanding type 2 diabetes broadly confirms what we already know – namely that substantial weight loss if largely sustained can substantially improve sugar levels, in some to the point of where diabetes may be considered to be resolved, as well as improvements in related heart risk factors (lipids) and patients’ quality of life.  The patients also then didn’t need to take as much medication.

“More importantly, the surgery undertaken seemed to be safe and there appeared to be few major health issues in the long term.  In other words, losing large amounts of weight (~15-20%) reverses many of the features of diabetes which fits with what we know that diabetes is a disease of excess fat building up in key organs.

“Of course, big weight loss using diet changes and low energy liquid diets early in the course of diabetes is also being trialed to reverse diabetes and, if successful in the longer term, many patients may prefer this route.  Whatever the result, it now abundantly clear that weight gain begets diabetes in those at risk and sustained big weight loss – whether by diet or surgery – can make huge improvements in health of patients with diabetes.  We now need ways to integrate these findings into clinical practice.”

Prof. Francesco Rubino, Chair of Metabolic and Bariatric Surgery, King’s College London, said:

“The STAMPEDE trial adds to a large and growing body of evidence including at least 12 other randomized clinical trials that have so far compared surgery and medical therapy head to head in the treatment of type 2 diabetes. The study is, however, one of only two such trials that have now reached the 5-year mark, a significant timeframe to assess the durability of diabetes improvement as well as safety of surgery. STAMPEDE is also the only randomized trial with 5-year data that included patients with only mild obesity or merely overweight.

“The study compared the use of two types of surgical operations (sleeve gastrectomy and gastric bypass) versus intensive medical therapy and lifestyle modifications.  The results show that surgical treatment is safe and can cause major and durable improvement of diabetes; surgery proved superior to drug regimens not only in controlling blood sugar levels but also in reducing cardiovascular risk factors and improving patients’ quality of life. Importantly, patients treated surgically used significantly less medication or no medication throughout the 5 years of the study. This was true not only for glucose-lowering drugs and insulin, but also for lipid-lowering drugs and drugs for high blood pressure. This finding highlights how surgery can be a very cost-effective approach for diabetes treatment.

“In keeping with a similar randomized clinical trial previously published in the Lancet and conducted by researchers in Rome in collaboration with us here at King’s College London, the STAMPEDE study shows that even patients that after 5 years experienced relapse of diabetes after initial and complete remission of the disease continue to maintain excellent control of their blood sugar levels with minimal or no need for glucose lowering drugs.

“While the study gives a robust measure of the differences in long-term control of glycemia (the primary endpoint of the study), the trial was not robust enough to study the effects of the interventions on other outcomes. For instance, even if in this study surgery appears to outperform medical management in terms of reduction of overall cardiovascular risk, the size of the study was too small to verify if such decrease in the risk of developing cardiovascular disease does translate in lesser incidence of actual cardiovascular events such as heart attacks and strokes. Previous, larger but non-randomised studies have suggested that this may be the case (i.e. the SOS study from Sweden and other similar studies from the USA) but no randomised trials to date have been conducted to look at cardiovascular events as primary endpoints. Given the incidence of such events per year, it would require a much larger randomised trial than STEMPEDE to detect differences in hard cardiovascular endpoints.

“Also, despite the 3-arm design, the STAMPEDE trial was not originally aimed at measuring differences between the two surgical procedures (sleeve gastrectomy and gastric bypass) but only between surgery (using two procedures) and conventional management of diabetes. This means that the study was not powered enough to conclude that the two procedures are equally effective on diabetes. In fact, even if rates of diabetes remission and levels of blood sugar levels are relatively similar between surgical groups, the patients who underwent gastric bypass needed significantly less medication to achieve control of diabetes than those that underwent sleeve gastrectomy, suggesting that gastric bypass may have greater anti-diabetic potential compared to sleeve gastrectomy.  This observation is consistent with other clinical and translational studies that have previously shown how the changes in the anatomy of the small intestine (typical of gastric bypass but not of sleeve gastrectomy) bring about additional mechanisms and effects on glucose metabolism, in addition to those deriving from weight loss or from stomach restriction itself. Sleeve gastrectomy and gastric bypass are currently the most commonly performed operations for obesity. Further studies comparing these two procedures head to head will inform clinicians about how to choose the best operation in different clinical scenarios when diabetes is the primary concern. For now, the study is reassuring that both operations can have significant benefits in patients with diabetes.

“The ability of surgery to reduce patients’ dependency on drugs and insulin therapy has both medical and economic implications.  Type 2 diabetes is in fact a progressive disease that typically worsens over time, requiring increasingly complex and expensive drug regimens while leading to debilitating and costly complications.  Despite the growing evidence of its effectiveness, many diabetes care providers and patients are still inadequately informed about the indications and potential benefits of surgical treatment for obesity and type 2 diabetes.

“For all its advantages, however, surgery is not amenable as a mass treatment option.  Further studies are necessary to identify exact clinical scenarios for which surgery could be prioritized as a first line of treatment.  Given the extraordinary and unique ability of surgery to cause remission of the disease, improving our understanding of how surgery works may be our best opportunity to understand how diabetes itself works.  This knowledge can lead to less invasive future approaches for treatment and more effective prevention strategies.

“These results from the STAMPEDE trial corroborate and expand the substantial body of evidence that has recently led to the development of global clinical guidelines for surgical treatment of diabetes.  Publication of the STAMPEDE trial comes just weeks after the American Diabetes Association (ADA) included metabolic surgery in their 2017 Standards of Medical Care in Diabetes, recommending consideration of surgery for patients with type 2 diabetes and BMI >30 kg/m2 (or 27.5 for Asian subjects) especially when other therapies are not sufficient to achieve adequate control of blood sugar levels.  The recent move by the ADA follows recommendations from the Diabetes Surgery Summit (DSS), also endorsed by 46 scientific societies from worldwide, including Diabetes UK and the International Diabetes Federation (IDF).

“There is clear biological and clinical evidence that type 2 diabetes is an operable disease and this explains why major diabetes organisations now recognise metabolic surgery as a mainstream diabetes treatment.  It is crucial that GPs, policy makers and the public at large be made aware of the new guidelines and their supporting evidence. Eligible patients should now have adequate access to a clinically proven and cost-effective form of diabetes treatment.”

* ‘Bariatric surgery versus intensive medical therapy for diabetes — 5-year outcomes’ by Philip R. Schauer et al. will be published in the New England Journal of Medicine on Wednesday 15 February 2017.

Declared interests

Prof. Nick Finer: “Prof Finer declares that he is employed by Novo Nordisk a manufacturer of diabetes and weight loss medications.”

Prof. Naveed Sattar: “Naveed Sattar is CO-I on trial of DiRECT trial which is testing very low energy diets in the reversal of diabetes early in the course of the disease.”

Prof. Francesco Rubino: “Professor Rubino is also Consultant Surgeon at King’s College Hospital.  He was the main organiser and co-director of the Diabetes Surgery Summit, an influential international consensus conference that recently developed global clinical guidelines for surgical treatment of diabetes.  Disclosures: employment – King’s College London.  Grant funding – NIHR, Ethicon.  Memberships: BOMSS, ASMBS, ADA, SSAT (professional medical and surgical societies).  Other financial interests – consultant for Ethicon, Fractyl.  Prof Francesco Rubino is one of the pioneers of surgical treatment of type 2 diabetes, also referred to as metabolic surgery. His experiments provided the first evidence of a direct link between surgical alterations of gastrointestinal anatomy and glucose metabolism, supporting the idea of using bariatric surgery as a specific diabetes therapy. He was the main organizer and co-director of the Diabetes Surgery Summit, an influential international consensus conference that recently developed global clinical guidelines for surgical treatment of diabetes.  In 2013 he joined King’s College London, becoming the world’s first Professor of Metabolic and Bariatric Surgery.”