The Surgical Therapy and Medications Potentially Eradicate Diabetes Efficiently (STAMPEDE) Substudy

An Interview with Study Authors Philip Schauer, MD, and Sangeeta Kashyap, MD
Dr. Schauer is the Director of the Bariatric and Metabolic Institute, Cleveland Clinic, Cleveland, Ohio. Dr. Sangeeta Kashyap is Associate Professor of Medicine, Cleveland Clinic Lerner College of Medicine, Cleveland, Ohio.

Bariatric Times. 2013;10(7):14–15.

FUNDING: No funding was provided in the preparation of this manuscript.

FINANCIAL DISCLOSURES: The authors reports no conflicts of interest relevant to the content of this article.

Background on STAMPEDE
Published in 2010, the Surgical Therapy and Medications Potentially Eradicate Diabetes Efficiently (STAMPEDE) study1 compared the efficacy of intensive medical therapy (IMT) alone with intensive medical therapy combined with two bariatric surgery procedures, laparascopic sleeve gastrectomy (LSG) and Roux-en-Y gastric bypass (RYGB), in patients with type 2 diabetes mellitus (T2DM) with modest obesity (BMI of 27–42kg/m2).

After 12 months, the researchers measured the main study outcome: glycohemoglobin (HbA1c)<6.0%. They found that among the groups, 12 percent of the medical-therapy group, 42 percent of the RYGB group, and 37 percent of the LSG group receached HbA1c<6.0%. They concluded that 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.
In an extension of the STAMPEDE trial, published February 2013 in Diabetes Care,[2] Kashyap et al report the two-year follow-up results of 60 original trial participants. In this substudy, they evaluated the effects of the three treatments (IMT, RYGB, and LSG) on glucose regulation, pancreatic beta-cell function, and body composition.

BT: During the first STAMPEDE trial, were you surprised that RYGB patients showed the greatest improvement in HbA1c?

Drs. Kashyap and Schauer: We were very impressed with the durability of the procedure at two years and were surprised that in the sleeve gastrectomy group there was a relapse in glycemic control despite excellent weight loss results similar to that of gastric bypass.

BT: Do you feel the original STAMPEDE findings have changed options in the treatment of T2DM?

Drs. Kashyap and Schauer: Yes. For patients who are obese and medically refractory with uncontrolled type 2 diabetes on insulin, bariatric surgery presents a superior option.

BT: When conducting the original STAMPEDE study, did you already plan on following up with these patients two years later?

Drs. Kashyap and Schauer: Yes, this was a pre-planned analysis

BT: Why was it important to take a closer look at glucose regulation, pancreatic beta-cell function, and body composition in the STAMPEDE participants?

Drs. Kashyap and Schauer: Beta cell failure defines the pathophysiology of T2DM, and determining the surgical effects on beta cell function is critical.

BT: You state in the substudy paper that RYGB in particular uniquely restores normal glucose tolerance and pancreatic beta-cell function. What makes RYGB the most effective treatment here? Is it in the mechanics of the procedure and its specific effect on insulin sensitivity and glycemic control?

Drs. Kashyap and Schauer: RYGB restores both insulin sensitivity and secretion, and this was linked to abdominal fat loss.

BT: How far away are we from RYGB being the treatment of choice of patients who have T2DM and moderate obesity?

Dr. Kashyap:  It is already approved for those with BMI of 35 and greater.

Dr. Schauer:  The STAMPEDE trial showed that patients with a BMI as low as 27kg/m2 with uncontrolled T2DM had superior glycemic control compared to ITM alone. Limiting bariatric surgery to individuals who need to lose a lot of weight may be changing based on the STAMPEDE results and other studies in patients with BMIs between 30 and 35kg/m2. For instance, Cleveland Clinic expanded its employee health insurance coverage of bariatric surgery to include individuals with uncontrolled T2DM and a BMI of 30kg/m2. Effective July 1, 2012, Cleveland Clinic employee health insurance plan covers bariatric surgery for an individual with a BMI between 30 and 35kg/m2 as long as their diabetes is not well controlled with medications alone and they have been under the care of an endocrinologist for at least six months.

BT: Are there plans to do a second follow up with these same patients two years from now?

Drs. Kashyap and Schauer: Yes, this is in the works.

BT: Are there currently other substudies of STAMPEDE being conducted?

Drs. Kashyap and Schauer: Yes, there is a cardiovascular substudy that is in the works.

BT: Do you recommend bariatric surgeons share these findings with their local group of endocrinologists, cardiologists, primary care physicians? What is the importance of sharing the findings with other specialties?

Dr. Kashyap: The trial indicates that bariatric surgery should be considered as a therapy for diabetic patients who fail to manage their diabetes with diet/exercise and medications. The hesitancy to refer patients to bariatric surgery stems from misconceptions about surgery on risk and mortality. If bariatric surgeons contact their local endocrinologist and share their success and failures, then clinicians will have confidence to refer patients for various therapies.

Dr. Schauer: Yes, many physicians have patients with T2DM and obesity who are not well controlled with optimal medical therapy. These recent findings will provide clinicians with the knowledge that surgery is another powerful tool in their tool box to more effectively treat diabetes and prevent severe complications.

BT: Could this potentially change the number of referrals that bariatric surgeons receive from other healthcare professionals?

Dr. Kashyap: In the last decade, the number of referrals for the treatment of morbid obesity has grown exponentially, and this is due to a wide number of publications that highlight the benefits of surgery for patients with morbid obesity and metabolic disease.

Dr. Schauer: Yes, since only 50 percent of patients with diabetes and obesity are in good glycemic control with medical therapy, one would expect more referrals to surgery in order to prevent complications related to poor glycemic control. The risk of surgery of course should always be considered when a surgeon is recommending metabolic surgery.

BT: Do these results fit in with other similar studies or is it a stand-alone study?

Dr. Kashyap: When the trial was published in the New England Journal of Medicine in March 2012, it was a stand alone in the sense that the design was a randomized, controlled trial that demonstrated that surgery was clearly more effective than medical therapy, whereas many other studies are case series or observations collected on a group of patients.

Dr. Schauer: Nowadays, there are three randomized controlled trials (Dixon, Mingrone, Schauer/Kashyap)[1–4] showing superior results of surgery compared to medical therapy in the short term. These results are also compatible with the prospective controlled Swedish Obesity Subjects (SOS) study that shows surgery reduces long-term mortality associated with obesity and diabetes.

BT: Do you hope these results change the way people think about bariatric surgery?

Dr. Kashyap: Although patients realize that surgery is effective in treating diabetes and belly fat, it is still an invasive, nonreversible procedure associated with significant cost and hospitalization that means time away from work. I believe that more patients will strongly consider bariatric surgery than before and should discuss their concerns with their medical providers.

Dr. Schauer: I think the mindset of physicians, surgeons, and patients is definitely changing. That’s why the term “metabolic surgery” is gaining preference over bariatric surgery because it’s not just about weight loss, it’s about improvement or resolution of metabolic disease such as diabetes.

BT: Do you see these results as having a profound effect on patients’ lives?

Dr. Kashyap: Yes. Studies have shown increase in quality and extension of life in patients with morbid obesity.

Dr. Schauer: Yes, both the numerous observational studies and the recent randomized trials all show profound health benefits, improved quality of life, and improved longevity.

BT: Drs. Kashyap and Schauer, thank you for taking the time to speak with us.

References
1.    Schauer PR, Kashyap SR, Wolski K, et al. Bariatric surgery versus intensive medical therapy in obese patients with diabetes. N Engl J Med. 2012;366(17):1567–1576. Epub 2012 Mar 26.
2.    Kashyap SR, Bhatt DL, Wolski K, et al. Metabolic effects of bariatric surgery in patients with moderate obesity and type 2 diabetes: analysis of a randomized control trial comparing surgery with intensive medical treatment. Diabetes Care. 2013 Feb 25. [Epub ahead of print]
3.    Dixon JB, O’Brien PE, Playfair J, et al. Adjustable gastric banding and conventional therapy for type 2 diabetes: a randomized controlled trial. JAMA. 2008;299(3):316–323.
4.    Mingrone G, Panunzi S, De GA, et al. Bariatric surgery versus conventional medical therapy for type 2 diabetes. N Engl J Med. 2012;366(17):1577–1585. Epub 2012 Mar 26.

Category: Interviews, Past Articles