Metabolic Surgery is Here to Stay: Five-Year Data Released Demonstrating Continued Durability, Superiority of Glycemic Control after Metabolic Surgery
An Interview with
Sangeeta Kashyap, MD
Professor of Medicine, Cleveland Clinic Lerner College of Medicine; Staff Physician, Department of Endocrinology, Cleveland Clinic, Cleveland, Ohio
The STAMPEDE (Surgical Therapy And Medications Potentially Eradicate Diabetes Efficiently) trial is the largest single center randomized trial with one of the longest follow-ups comparing medical therapy with bariatric surgery. Last month, Philip Schauer, MD, lead author, presented the STAMPEDE trial’s final results during the American College of Cardiology’s 65th Annual Scientific Session (ACC.16).[1] Recently, final five-year data was published in New England Journal of Medicine.[2]
STAMPEDE is a three-arm controlled trial conducted by investigators from Cleveland Clinic, Cleveland, Ohio, that randomized 150 patients with obesity and uncontrolled type 2 diabetes mellitus (T2DM) to receive either intensive medical therapy alone or intensive medical therapy plus Roux-en-Y gastric bypass (RYGB) or laparoscopic sleeve gastrectomy (LSG). The primary end point was a glycated hemoglobin level of 6.0% or less. One- and three-year outcomes[3,4] concluded that among patients with obesity and uncontrolled T2DM, intensive medical therapy plus bariatric surgery resulted in glycemic control in significantly more patients than did medical therapy alone. The final, five-year outcomes report confirms these findings.
Bariatric Times interviewed Sangeeta Kashyap, MD, co-author on the trial, for her insight on STAMPEDE, its final results, and what they mean for the field of metabolic surgery.
Dr. Kashyap, thank you for taking the time to discuss STAMPEDE and its final results. Why are five-year results important and what are the trial’s key takeaways?
Dr. Kashyap: These final results are very important because five years marks the time when we can really conclude if there is durability of the procedures to help control diabetes. Although we did observe relapse in some patients, our results indeed showed continued durability of glycemic control after metabolic surgery as well as persistent weight loss and reductions in diabetes and cardiovascular medications at five years. Both sleeve and gastric bypass had similar metabolic benefits and greater benefits were seen for those with shorter duration of diabetes prior to surgery.
Final outcomes also confirmed our previous findings that intensive medical therapy plus bariatric surgery results in better glycemic control than medical therapy alone. The bottom line is that there are limits to intensive medical therapy for diabetes, especially when patients are overweight. For refractory patients, surgery is a superior option.
Can you provide more detail regarding patients who experienced T2DM remission relapse?
Dr. Kashyap: Throughout the trial, T2DM remission was defined as a glycated hemoglobin level of 6.0% or less. We found that the percentage of patients who hit remission dropped at five years as compared to the first year.
In the one-year results, the remission rates were as follows: 12 percent in the medical-therapy group, 37 percent in the sleeve gastrectomy group, and 42 percent in the gastric bypass group.
At five years, remission dropped to five percent in the medical-therapy group, 23 percent in the sleeve gastrectomy group, and 29 percent in the gastric-bypass group. This shows that both procedures were equally effective and as effective as each other, though the relapse rate was slightly higher with the sleeve. Also, there was considerably more weight loss in the surgical groups (particularly gastric bypass) as compared to the medical group.
What do these results tell us about weight regain and patients’ risk for remission relapse after surgery?
Dr. Kashyap: We measured weight regain among STAMPEDE patients and are planning to conduct it as an ancillary study.
Five-year results tell us that the rates of remission do diminish over time after surgery and it’s important to talk to patients about their expectations. We see that the people who relapse typically have longer duration of diabetes (> 8 years) and tend to lose less weight initially than those who don’t relapse. So, weight loss has been shown to be the most important modifiable factor in driving diabetes improvement. At Cleveland Clinic, we encourage our patients to keep exercising, eating healthy, and following recommendations long after their procedures.
Weight regain is something that we as clinicians have to deal with because weight regain in a RYGB or LSG patient means that they are at risk for diabetes recurrence.
How else might you help patients achieve good initial weight loss and prevent weight regain after surgery? How might you help a patient who experienced remission relapse following surgery get back into remission?
Dr. Kashyap: During STAMPEDE, all patients received intensive medical therapy. “Intensive medical therapy,” included lifestyle counseling, weight management, frequent home glucose monitoring, and the use of newer drug therapies approved by the Food and Drug Administration (FDA). Many of my patients—surgical and nonsurgical—are self-monitoring their weight loss. I find that people who self monitor and show up to their appointments are the patients who are continuously trying, and thus achieving weight loss/HbA1c goals.
After surgery, I tell patients, “Listen, you’ve had surgery. I can still consider you diabetic, but you’re diet controlled. As long as you adhere to the program, exercise, and continue to keep the weight off, you may be able to see remission. But once you start regaining weight, you gain fat, and that is when blood sugars start rising again.” I think we have to be really aggressive with weight loss—even after surgery is done—that is the important point for clinicians and patients.
To get patients back into T2DM remission, I usually have to put them on medications, such as metformin. We might also consider utilizing anti-obesity drugs, such as glucagon-like peptide-1 receptor agonists (GLP-1) and SGLT-2 inhibitors, which may alleviate cravings or weight gain.
Do investigators believe there is a reason as to why gastric bypass shows better glycemic control versus sleeve gastrectomy?
Dr. Kashyap: Again, our results show that the driving factor is weight loss—the greater the weight loss, the greater the improvement in T2DM.
In this trial, we got the most weight loss with RYGB. I think RYGB is still gold standard for improving diabetes, but obviously LSG did fairly well too. I think that is one reason LSG is on the rise. Patients seem to like it more than the bypass.
I think most patients will prefer to have a sleeve perhaps because it is technically easier for the surgeon to perform and appears to have less gastrointestinal complications .In STAMPEDE, LSG did well, but the RYGB showed superior results when it came to improving insulin secretion and sensitivity.
When you look at just the surgical groups, people with earlier duration of diabetes have a better outcome. This makes sense because the pancreas and beta cells are still somewhat functional and able to make insulin. With the RYGB, the amount of fat in the abdominal organs—pancreatic fat, abdominal fat, liver fat—may be reduced more than with LSG. Our previous STAMPEDE results showed that at two years, weight loss being observed from both procedures was fairly similar, but we started seeing greater abdominal weight loss in the RYGB group. I think there’s better fat loss in the pancreas and liver and this is why we are getting better blood sugar control/not needing medications with the RYGB. It all boils down to body weight and fat loss. It’s just better with RYGB, and I believe it may have something to do with bypassing the intestine.
I’m currently involved in research observing the following patient groups following bariatric surgery: 1) those who hit T2DM remission, 2) those who never obtained remission following surgery, and 2) those who hit remission but then fell out of it after the first year. I can tell you the answer is weight—the amount of weight loss is critical. I think the abdominal fat loss, and not so much body mass index (BMI), is what is really linked to T2DM.
You bring up an interesting point—measuring weight loss success using BMI. Did STAMPEDE measure BMI? What are your thoughts on its use?
Dr. Kashyap: I think BMI is crude and possibly not the best measure of weight loss success. For patients with metabolic disease, waist circumference and fasting insulin levels are indicators of insulin resistance and metabolic disease.
During STAMPEDE planning, when we looked at all the factors at baseline and asked which factors really account for remission versus non-remission, BMI was not among them. When you looked at people with BMI under 35kg/m2 versus those with a BMI greater than 35kg/m2, BMI did not make the difference in terms of achieving remission. Our data certainly supports that people with BMIs 35kg/m2 and below with T2DM have the same chance for improvement, provided they lose an adequate amount of weight, whether with surgery, weight loss devices, and/or pharmacotherapy and behavioral changes.
As an endocrinologist, what do you find most impactful about the STAMPEDE trial’s final results?
Dr. Kashyap: We’ve known all along that if you can help people lose at least 5 to 10 percent of their body weight, you can improve diabetes. What surgery shows us is that in the setting of early duration of disease, when you get people to lose a lot of weight—at least 20 to 25 percent of their body weight—you can put the disease to rest for up to five years without needing medication, especially insulin, which is very burdensome and can cause weight gain and low blood sugar. To me, this is the most innovative finding and the greatest takeaway of STAMPEDE. I was also pleased that the trial showed 1) quality of life improvement and 2) reduction in medications needed for blood pressure and cholesterol in patients following surgery.
As a medical doctor, I am still concerned about weighing the risks and benefits of surgery. In the risk/benefit equation, it’s important to consider the rate of reoperation, nutrition problems (e.g., anemia), osteomalcia/osteoporosis, and late complications, such as bowel obstructions, strictures, and fistulas. All of these risks make medical doctors and patients weary of surgery. In some cases, patients may be trading in one problem (e.g., T2DM) for another (e.g., gastric ulcer) related to undergoing abdominal surgery. That risk/balance equation has to be individualized and carefully discussed because although the benefits are definitely there for surgery, it is still surgery and a lot of patients aren’t ready for it.
In my practice, most patients with BMIs under 35kg/m2 are not really interested in surgery. If they are 30 to 40 pounds overweight, they would much rather try nonsurgical means before considering surgery. I find that patients are aware of the comorbidities of overweight and obesity and understand that they really impact their health and life. There are still people out there with very high BMIs who are not getting surgery that could benefit from it. I think although our results show there may be similar benefits for people with BMIs under 35kg/m2, the focus should still be on people with higher BMI as the public health need is still great for this patient population.
What do you think about nonsurgical devices as a means for treatment in patients with BMIs 35kg/m2 and below with T2DM?
Dr. Kashyap: I I think things like the intestinal liner, intragastric balloons, and any other device or therapy that helps people lose weight, especially when their diabetes is fairly early, is going to result in some improvement if not remission. The big question we haven’t answered yet is exactly how much weight do people need to lose to get into T2DM remission? Is it 10 percent of your body weight? 15 percent? What is the magic number? I think it would be good to know.
It would also be good to know the etiology of weight regain so we can determine the best means of intervention. Sometimes weight regain is related to life stressors or depression, in which case a patient might benefit from being referred back to the psychologist or dietitian. A multidisciplinary approach after surgery, and after they achieve remission, is often necessary.
Do you feel endocrinologists are now more aware of the benefits of bariatric surgery?
Dr. Kashyap: Absolutely. I think that endocrinologists are now being trained at most of the national meetings—ADA, Endocrine Society. There are always talks about bariatric surgery—how to manage the post bariatric surgery patient, how to deal with weight regain, and barriers to care.
What are examples of barriers to care?
Dr. Kashyap: First, I think it’s the patients themselves that create barriers to their own care. A patient has to be willing to consider treatment, including surgery. As mentioned previously, I find that patients have a real fear of having a permanent, irreversible surgery. It means changes in the way they eat and behave, which is a scary thing for a majority of patients. It requires a lot of thought.
The patients are their own worst enemy. We are the ones that really try to counsel them. For example, I talk to them about durability. When a patient expresses that they want to try diet, behavior modifications, and pharmacotherapy, I help them to manage weight loss expectations for each therapy. For instance, with the diet and pharmacotherapy, they will likely be able to lose 10 to 12 percent of body weight, but this is a huge difference compared to the 25 to 30-percent weight loss they would likely be bale to achieve with bariatric surgery.
Next, there is a barrier in referring patients for surgery, which is mostly due to insurance coverage and financial issues.
With the STAMPEDE trial completed, what is the next area of research in which you are applying your focus?
Dr. Kashyap: Unfortunately, our study was too small and we did not see any changes in the rate of retinopathy, nephropathy, or any other complications of diabetes. We didn’t see any changes in renal function or retinopathy, which is what most endocrinologists want to see. So, the next big question is, “Can bariatric procedures affect end organ damage related to diabetes?” I am currently involved in the Alliance of Randomized Trials of Medicine vs Metabolic Surgery in Type 2 Diabetes (ARMMS-T2D). Through this project, we will examine data from four sites—Cleveland, Ohio, Pittsburgh, Pennsylvania, Seattle, Washington, and Boston, Massachusetts. This project is valuable because it will give us a larger sample size—around 300 patients. You can learn more about ARMMS-T2D at https://clinicaltrials.gov/ct2/show/NCT02328599.
Do you have any final words about the STAMPEDE trial’s final results?
Dr. Kashyap: I think these data are really important. The fact that you can see durability of results tells me that metabolic surgery is here to stay. Endocrinologists as well as other members of the multidisciplinary care team should continue to work closely with surgeons to try to optimize weight loss and T2DM outcomes in patients.
Editor’s Note: Article containing full STAMPEDE Study results were in press at the time this interview was conducted.
references
1. Schauer PS. American College of Cardiology’s 65th Annual Scientific Session. Chicago, Illinois; April 2–4, 2016.
2. Schauer PR, Bhatt DL, Kirwan JP, et al. Bariatric surgery versus intensive medical therapy for diabetes – 5-year outcomes. N Engl J Med. 2017;376(7):641-651.
3. 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.
4. Schauer PR, Bhatt DL, Kirwan JP, et al. Bariatric surgery versus intensive medical therapy for diabetes—3-year outcomes. N Engl J Med. 2014;370(21):2002–2013. Epub 2014 Mar 31.
Funding: No funding was provided in the preparation of this manuscript.
Financial disclosures: The author reports no conflicts of interest relevant to the content of this article.
Category: Interviews, Past Articles
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