On 2017 Apr 28, SANGEETA KASHYAP commented:

I appreciate the comment by Dr. Weiss as medical therapy for diabetes is constantly evolving and improving. However, patients enrolled in this trial were poorly controlled despite using 3 or more glucose lowering agents at baseline including over half requiring basal bolus insulin. This coupled with the fact that two thirds had class 2 or greater severity of obesity, made them somewhat refractory to IMT. It is unlikely that patients like these would ever be able to maintain therapeutic targets of tight glycemic control for five years. Those that do, obviously should not consider bariatric surgery. Being in a rigorous clinical trial as this, all subjects had benefits of care that many real world patients do not and develop complications of the disease. Although the medical algorithm developed for this trial incorporated elements from ACCORD, titration of medical therapy was in some ways patient driven in that weight gain and hypoglycemia limit adherence to therapy. In medically refractory patients like this, surgery was more effective in treating hyperglycemia for five years with less medications overall.

On 2017 Apr 03, JOHN KIRWAN commented:

The success of the medical-therapy-alone arm in the STAMPEDE trial is clearly evidenced by the data, i.e., a 1.7% reduction in HbA1c at 1-year in this patient group. When one considers that RCTs evaluating the effectiveness of diabetes medications alone report HbA1c reductions of <1.0%, the outcome for the combined drug/lifestyle/education approach in STAMPEDE is consistent and it could be argued, is superior to most pharmacotherapy interventions currently reported in the extant-literature. If one looks at this from a slightly different perspective and compares the medical therapy arm of STAMPEDE to LookAHEAD, another intensive intervention (exercise/diet/education and pharmacotherapy) for obese patients (average BMI 36 kg/m2) with type 2 diabetes where the reduction in HbA1c was less than 1% at 1 year, then like the previous example, it is clear that the medical-therapy-alone arm in STAMPEDE was highly effective.

On 2017 Apr 02, Deepak Bhatt commented:

Having been involved with designing several trials, I would state that the control arm of STAMPEDE did indeed provide optimal medical therapy which exceeded what is generally obtained in real world practice. Randomized trials of surgical procedures are relatively uncommon, and STAMPEDE has helped greatly advance knowledge of the benefits of metabolic surgery. Adherence to polypharmacy is understandably challenging for many patients, and surgery gets around this barrier quite effectively. Furthermore, this landmark trial should not be viewed as surgery versus medical therapy, but rather surgery versus no surgery on a background of excellent medical therapy.

On 2017 Apr 01, PHILIP SCHAUER commented:

I beg to differ with Dr. Weiss in that the control group of our study was provided intensive, multi-agent medical therapy as tolerated with an intent to reach a HbA1c < 6%- as per ACCORD. Furthermore, medication choice, intensification, dose and frequency were managed by a highly qualified, experienced team of expert endocrinologists at an academic center. A favorable decrease in HbA1c by 1.7% from baseline (> 9% HbA1c) was achieved initially in the control group which was already heavily medicated at baseline (average of 3+ diabetes drugs). Thus, many would agree that our approach was "intensive". This initial improvement, however, was not sustained possibly due to inherent limitations of medical therapy related to adherence, side effects, and cost. Surgery is much less adherence-dependent, which likely accounts for some of the sustained benefit of surgery. Many will disagree with Dr. Weiss that ACCORD defines “true intensive medical therapy” since that regimen actually increased mortality compared to standard therapy, likely due to drug related effects (eg. hypoglycemia). On the contrary, more than 10 comparative, non-randomized studies show a long-term mortality reduction with surgery compared to medical therapy alone (1). New, widely endorsed guidelines by the American Diabetes Association and others now support the role of surgery for treating diabetes in patients with obesity, especially for patients who are not well controlled on medical therapy (2). 1)Schauer et al.Diabetes Care 2016 Jun;39(6):902-11 2)Rubino et al. Diabetes Care. 2016 Jun;39(6):861-77

On 2017 Mar 15, Daniel Weiss commented:

The benefit of weight loss on glycemic control for those with Type 2 Diabetes has been recognized for decades. The five-year outcomes of STAMPEDE are not surprising. However there was a major flaw in the design of this trial: despite its title, the control group was not provided “intensive medical therapy”.

The primary outcome was to compare “intensive medical therapy” alone to bariatric surgery plus medical therapy in achieving a glycated hemoglobin of 6% or less. The medical therapy group was seen every 3 months and had minimal increase in medications (mean of 2.8 medications at baseline and 3 at one year). And, at the one-year and five year time points, substantially fewer patients were on insulin as compared to baseline. At one year, 41 percent were on a glucagon-like peptide-1 receptor agonist.

Minimally intensified medical therapy obviously would bias results toward surgery. True intensive medical therapy as in the landmark ACCORD trial (Action to Control Cardiovascular Risk in Diabetes) involved visits every 2-4 weeks with actual medication intensification.

Reference The Action to Control Cardiovascular Risk in Diabetes Study Group. Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med 2008;358:2545-59.

On 2017 Mar 15, Daniel Weiss commented:

The benefit of weight loss on glycemic control for those with Type 2 Diabetes has been recognized for decades. The five-year outcomes of STAMPEDE are not surprising. However there was a major flaw in the design of this trial: despite its title, the control group was not provided “intensive medical therapy”.

The primary outcome was to compare “intensive medical therapy” alone to bariatric surgery plus medical therapy in achieving a glycated hemoglobin of 6% or less. The medical therapy group was seen every 3 months and had minimal increase in medications (mean of 2.8 medications at baseline and 3 at one year). And, at the one-year and five year time points, substantially fewer patients were on insulin as compared to baseline. At one year, 41 percent were on a glucagon-like peptide-1 receptor agonist.

Minimally intensified medical therapy obviously would bias results toward surgery. True intensive medical therapy as in the landmark ACCORD trial (Action to Control Cardiovascular Risk in Diabetes) involved visits every 2-4 weeks with actual medication intensification.

Reference The Action to Control Cardiovascular Risk in Diabetes Study Group. Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med 2008;358:2545-59.

On 2017 Apr 28, SANGEETA KASHYAP commented:

I appreciate the comment by Dr. Weiss as medical therapy for diabetes is constantly evolving and improving. However, patients enrolled in this trial were poorly controlled despite using 3 or more glucose lowering agents at baseline including over half requiring basal bolus insulin. This coupled with the fact that two thirds had class 2 or greater severity of obesity, made them somewhat refractory to IMT. It is unlikely that patients like these would ever be able to maintain therapeutic targets of tight glycemic control for five years. Those that do, obviously should not consider bariatric surgery. Being in a rigorous clinical trial as this, all subjects had benefits of care that many real world patients do not and develop complications of the disease. Although the medical algorithm developed for this trial incorporated elements from ACCORD, titration of medical therapy was in some ways patient driven in that weight gain and hypoglycemia limit adherence to therapy. In medically refractory patients like this, surgery was more effective in treating hyperglycemia for five years with less medications overall.