March 17, 2016

expert reaction to study investigating bariatric surgery, lifestyle and medication interventions and remission of type 2 diabetes

Publishing in the journal Diabetologia a group of researchers have compared gastric surgery with lifestyle and medical interventions for the treatment of type 2 diabetes. In the trial with 32 patients the authors report that the group which received surgery saw greater remission of diabetes. A Before the Headlines analysis accompanied these comments.

Prof. Nick Finer, Honorary Professor at UCL, and Senior Principal Clinical Scientist with Novo Nordisk, said:

“Cummings and co-workers provide further evidence in support of the recent NICE position that expedited assessment for bariatric surgery should be offered to people with a Body Mass Index of 35 or above who have recent-onset type 2 diabetes.

“Their data from a well-conducted randomised trial (uncommon in the field of surgical treatment) showed that compared to an intensive lifestyle intervention, gastric bypass produced greater weight loss and a greater chance of patients being able to stop diabetes medications yet get excellent blood glucose control.

“However, the study also highlights many caveats. Firstly, the study only lasted one year and we know that with time the benefits of surgery on diabetes wane. Secondly only 43 of 1808 (2.4%) patients approached agreed or were eligible for surgery, and then 11 of these withdrew before the trial started. It is clear that many patients did not want to undergo gastric bypass surgery, whatever the potential benefits.

“While surgery produced greater weight loss and equivalent blood glucose control with fewer drugs compared to the lifestyle group, the authors give few details of the medical treatment patients received. This is important because there is an increasing number of diabetes drugs that also produce weight loss, as well as an increasing number of drugs available to produce weight loss, but we do not know if the lifestyle group had the benefits these might have given.

“Disturbingly the surgical group lost much more lean body mass (a bad thing) and this may have accounted for their failure to improve cardiorespiratory fitness unlike the lifestyle group, in whom this improved. Despite the greater weight loss and the need for fewer diabetes medications, there was no difference between the groups in terms of quality of life measured with a well validated questionnaire (the EQ5-D).

“So the study adds to evidence of the safety and efficacy of gastric bypass surgery in people with diabetes but highlights the needs for larger, longer-term studies that study real outcomes such as cardiovascular events (heart attack and stroke), cancer and mortality. Developments in medical diabetes and obesity treatment have and continue to rapidly evolve, and may soon (hopefully) be able to produce sufficient weight loss and glucose improvements that will obviate the need for bariatric surgery.”

Prof. Iain Broom, Director, Centre for Obesity Research and Epidemiology (CORE), Robert Gordon University, said:

“The paper is well written and the recruitment and randomisation procedures for the trial were well conducted, including the blind assessment. I have no problems with the science or the conclusions reached as far as the study design is concerned. The results conform to other similar studies but perhaps with possible slight bias in the recruitment of participants, as stated in the paper.

“I would take issue with the authors stating this was as an intensified lifestyle modification study as could be achieved. They use DPP (Diabetes Prevention Programme) or LookaHead dietary modifications, still based on extremely high carbohydrate intakes, even when it is known that within the diabetic population the level of weight loss expected is 50% of that in a non-diabetic population. They were thus creating bias in the outcomes, where from all published work they would expect a much slower rate of weight loss than that from bariatric surgery, and indeed could not expect to achieve a final weight loss anywhere near that of the surgical arm. Weight loss by this means in this population would not be expected to exceed 10% of initial body weight, and indeed in general would be much less than 10% (see the LookaHead study).

“It would have been more appropriate to compare a rapid weight loss approach over the first 3 months of dietary/intensive lifestyle followed by intensive behaviour/physical activity modification over the subsequent 9 months to achieve weight maintenance. This would have been much more equivalent to the weight loss characteristics of the surgical group. Such a pattern of weight loss could have been achieved by the use of a low energy diet, very low energy diet or low carbohydrate (<60g/day) diet, and where such dietary interventions are known to have the same weight loss in both the diabetic and non-diabetic populations (see Rolland et al Clin Obesity 3, 150-157). Likewise they are also associated with metabolic improvements akin to those seen with bariatric surgery (see Hession et al 2009 Obesity Reviews 10:36-50).

“It is clear from previous weight loss studies using non-surgical means that a weight loss of >15% body weight in 3 months is required to achieve remission of type 2 diabetes (see Lim et al 2011, Diabetalogica 54:2506-2514). Using standard “healthy eating” approaches cannot achieve this. This leaves the study as being inappropriate in terms of the comparison of the two arms.

“Both low energy diet (LED) or very low energy diet (VLED) (which are both low in carbohydrate), and low carbohydrate diets achieve improvement in insulin sensitivity independent of weight loss in a fashion similar to that of bariatric surgery, and are likewise associated with initial rapid weight loss and change in energy substrate metabolism seen with bariatric surgery.

“This was the wrong type of dietary control arm for this study labelled “intensive lifestyle and medical intervention” and the final outcome was inevitable and comes as no surprise. This does not help those individuals who are obese and have poorly controlled type 2 diabetes and who are not suitable for, or do not want bariatric surgery. This simply lends more inappropriate support to unnecessary surgical procedures where there is an intermediate lifestyle intervention that can and does work in both reducing weight and allowing remission of type 2 diabetes.”

Prof. Yoon Loke, Professor of Medicine and Pharmacology, Norwich Medical School, UEA, said:

“This is a very small study with only 32 patients. Follow-up was for a year, which seems a rather short time for a study looking at long-term conditions such as diabetes and obesity.

“The short follow-up and small numbers means that we do not know if the problem with diabetes will crop up again in future, of if the benefits of surgery are short-lived.

“Similarly, the study is too small to show whether surgery is safer or more dangerous than other treatments.

“The authors make a valid point that surgery can be beneficial irrespective of pre-existing BMI or other conditions.”

‘Gastric bypass surgery vs intensive lifestyle and medical intervention for type 2 diabetes: the CROSSROADS randomised controlled trial’ by David E. Cummings et al. will be published in Diabetologia on Thursday 17 March 2016. 

Declared interests

Prof. Nick Finer: Finer speaks on behalf of his position as a physician specialising in weight loss but is also employed by Novo Nordisk, a pharmaceutical company that markets several treatments including insulins and GLP-1 recptor agonists licensed for the treatment of diabetes and obesity.

Prof. Iain Broom: “I have no conflicts of interest in commenting on this paper.”

Prof. Yoon Loke: “I declare that I have no competing interests.”