March 26, 2012 (Chicago, IL and Cleveland, OH) ( UPDATED March 27, 2012 ) — Bariatric surgery performed considerably better than traditional medical therapy in obese patients with type 2 diabetes, independent of weight loss, according to findings from two randomized trials published online March 26, 2012 in the New England Journal of Medicine [1,2]. The larger of the two trials was also simultaneously presented here at the American College of Cardiology (ACC) 2012 Scientific Sessions.
In both studies, bariatric surgery induced remission and was associated with a significant improvement in metabolic control over and above medical therapy, both conventional and intensive,” say Dr Paul Zimmet (Heart and Diabetes Institute, Melbourne, Australia) and Dr George MM Alberti (King’s College Hospital, London, UK) in an accompanying editorial . “The studies . . . are likely to have a major effect on future diabetes treatment,” they add. Such procedures should no longer be considered as a last resort in diabetes and “might well be considered earlier in the treatment of obese people with type 2 diabetes. Who could predict that years after the discovery of insulin that surgeons would be challenging the physician’s territory for treating diabetes?”
I would hate to think of us jumping forward into this until we have a lot more data that this really changes the risk of these individuals for developing very serious complications of diabetes in the many years to come.
Zimmet and Alberti caution, however, that surgery is not yet “the universal panacea for obese patients with type 2 diabetes.” Both studies had relatively small sample sizes and short duration, which are important limitations, they note. And bariatric surgery is associated with perioperative risks and potential long-term problems due to micronutrient deficiencies, both of which need to be considered. More studies are needed, “particularly those that may provide better prediction of success and the expected duration of remission and long-term complications,” they conclude.
Others agreed. At the press conference following the ACC presentation of STAMPEDE, Dr Doug Weaver (Henry Ford Hospital, Detroit, MI) toldheartwire : “This is a relatively small study in a group of patients that was followed for a relatively short time. I would hate to think of us jumping forward into this until we have a lot more data [confirming] that this really changes the risk of these individuals for developing very serious complications of diabetes in the many years to come. That’s what’s missing here. Weight reduction and glucose are surrogates, but it’s not having less retinopathy, it’s not having fewer cases of renal failure that require dialysis, or other complications of diabetes. This is a pretty huge intervention to get glucose and weight control.”
STAMPEDE: Surgery reduces or eliminates need for diabetes meds
The Surgical Treatment and Medications Potentially Eradicate Diabetes Efficiently (STAMPEDE) study was reported by Dr Philip R Schauer (Cleveland Clinic, OH) as a late-breaking clinical trial today at the ACC meeting.
Schauer and colleagues enrolled 150 obese patients (BMI 27–43 kg/m2) with uncontrolled type 2 diabetes and randomly assigned them to medical therapy, Roux-en-Y gastric bypass (RYGB), or sleeve gastrectomy. Mean age was 49 years, and mean HbA1c was 9.2%.
The main study outcome of HbA1c <6.0% after 12 months of treatment was met by 12% of the medical-therapy group, 42% of the RYGB group (p=0.002 vs medical therapy), and 37% of the sleeve-gastrectomy group (p=0.008 vs medical therapy). Although glycemic control improved in all three groups, improvements were significantly greater in the surgical groups, as was weight loss and improvement in insulin resistance.
We need large randomized trials so we can have enough power to look at these events. Hopefully the NIH will look at this.
“There was quite a large difference between the surgical and medical group in terms of the success rate,” Schauer said during the ACC press conference following his presentation. “All of the gastric-bypass patients who reached HbA1c <6.0% did so without any medication; they were weaned off all the antidiabetics, including insulin, to reach that target.” They were also able to reduce cardiovascular-medication use, he noted. “That’s as close to a definition of remission that you can get. And the sleeve-gastrectomy group was pretty close as well.
“All in all, the take-home message is that these surgical patients enjoyed not only significant or superior improvement in glycemic control but they did so on much lower regimens of both diabetic and CV medications.”
However, Schauer acknowledged that there are few long-term data demonstrating any benefit of bariatric surgery on diabetic outcomes such as retinopathy. “We need large randomized trials so we can have enough power to look at these events,” he told heartwire . “Hopefully the [National Institutes of Health] NIH will look at this, because they are the one organization that really has the funding to do something like this.”
Effects attributed to mechanisms of surgery rather than weight loss
The second study, by Dr Geltrude Mingrone (Catholic University, Rome, Italy) and colleagues, involved 60 severely obese patients (BMI >35 kg/m2) aged 30 to 60 years with advanced type 2 diabetes randomly assigned to RYGB, biliopancreatic diversion (BPD), or conventional treatment (individualized medication therapy and strictly monitored diet and lifestyle interventions).
The main study outcome was remission, defined as fasting glucose <100 mg and HbA1c <6.5% for one year or longer, without the use of diabetes medication.
At two years, 95% of patients in the BPD group and 75% of those in the RYGB group had entered and maintained remission and were able to discontinue all diabetes medications. In contrast, none of the patients in the medical group had entered remission. Age, sex, baseline BMI, duration of diabetes, and weight loss after surgery did not predict diabetes remission or improvement in glycemia at one and three months.
“These findings confirm that the effects of bariatric surgery on type 2 diabetes may be attributed to the mechanisms of surgery rather than the consequences of weight loss,” Mingrone says in a statement. “Studying the actual mechanisms by which surgery improves diabetes may help understand the disease better.”
Senior author Dr Francesco Rubino (Weill Cornell Medical College, New York City) says: “Although bariatric surgery was initially conceived as a treatment for weight loss, it is now clear that surgery is an excellent approach for the treatment of diabetes and metabolic disease.”
Using BMI to define eligibility for surgery is “inappropriate”
Rubino adds that although BMI is correlated with the risk of developing diabetes in the general population, “in an individual, BMI does not tell much about the severity of diabetes, its potential to cause complications, or the mechanisms of disease. The study confirms that using strict cutoff BMI levels to define eligibility for surgery in patients with diabetes is medically inappropriate,” he notes.
Schauer agrees. “We have to consider these operations as antidiabetic procedures for diabetic patients, so there clearly are patients in the lower-BMI category in whom obesity is not the big problem,” he told heartwire .
But most guidelines indicate that bariatric surgery should be performed only in patients with type 2 diabetes who have BMIs of >35 kg/m2. The one exception to this is the International Diabetes Federation guidance, which last year changed to recommend that bariatric surgery could be considered as a reasonable treatment option in those with a BMI of 30 to 35 “if the patient has poorly controlled diabetes,” Schauer noted.
The first study was funded by the Catholic University of Rome, Italy. The second study was funded by Ethicon Endo-Surgery and others. Alberti has disclosed attending meetings funded by Ethicon. Disclosures for all authors and editorialists are available in the papers.