There has been a lot of publicity lately over the two articles released as online firsts this week in the New England Journal of Medicine. Both of these articles were single-center, randomized-controlled trials comparing bariatric surgery to intensive medical therapy in patients with type 2 diabetes. One trial was done at the Cleveland Clinic (link here) and another done in Italy (link here). Here is the NY Times article covering the story.
Italian study (Mingrone G et al.: Bariatric Surgery versus Conventional Medical Therapy for Type 2 Diabetes. NEJM 2012 Jan. 2)
This study took 60 patients with BMI more than 35, type 2 diabetes for more than 5 years, and hemoglobin A1c of >7% and split them into three groups. One group received gastric bypass, one group biliopancreatic diversion, and one group medical therapy. The primary end point was the “difference in the rate of remission of type 2 diabetes among patients undergoing either gastric bypass or biliopancreatic diversion, as compared with medical therapy.” They defined remission of diabetes as a fasting glucose of <100 mg/dl and an A1c of <6.5% for at least 1 year without active pharmacologic therapy.
One notable thing about this study was that the average BMI across all three groups was 45. The average A1c going into the study was 8.5%.
As you can see above, the A1c reduction in the two surgery groups was significantly better than the medical therapy group. In fact, every secondary end-point (other than blood pressure) was significantly improved with surgery rather than medical therapy. This includes cholesterol, weight, and waist circumference, among other end-points. In terms of the primary end-point, 0/20 patients achieved remission with medical therapy, compared to 15/20 with gastric bypass and 19/20 with biliopancreatic diversion. One thing I noticed is that the A1c curve above for gastric bypass starts to rise from 12 to 24 months and one wonders whether given another couple of years whether it might come closer to the medical therapy A1c curve.
Cleveland Clinic study (Schauer PR et al.: Bariatric Surgery versus Intensive Medical Therapy in Obese Patients with Diabetes. NEJM 2012 Jan. 2)
This was a larger trial than the one done in Italy, with 150 total patients instead of 60 total patients. Also notable is that the average BMI was 36, much smaller than the average BMI of 45 in the Italian study. The stated goal of medical management in this trial was “modification of diabetes medications until the patient reached the therapeutic goal of a glycated hemoglobin level of 6% or less or became intolerant to the medical treatment.” The two surgeries performed in this trial were gastric bypass and sleeve gastrectomy. The primary end-point was the proportion of patients with an HbA1c of 6% or less with or without diabetes medications a year after randomization. In this trial, the average HbA1c at trial start was 9%.
The medical group had a reduction in A1c to 7.5%, the surgical groups to about 6.5% (with statistical significance). Again, secondary end points like body weight and lipids were also significantly reduced in the surgical groups. This trial also demonstrated a dramatic decrease in the number of diabetes medications required in the surgical groups compared to the medical treatment group. I find that to be a useful outcome measure, since it is actually something that “means something” to patients. Not having to take medications anymore is a really big deal and a nice lifestyle change for lots of patients.
My take on these studies:
Are these studies going to change my practice? Probably not dramatically. I’ve already been practicing under the assumption that bariatric surgery is an excellent way of causing weight loss and “curing” a number of comorbid illnesses like diabetes. These trials give us a higher level of evidence to back that belief up than we’ve had before. So, on balance, maybe I’ll be a bit more likely to recommend that a patient consider bariatric surgery.
If I have beef with these studies, it is that in both of these studies, diabetes was treated as a categorical variable rather than a continuous one. The real significance of the diagnosis of diabetes is your risk for long-term complications such as nephropathy, retinopathy, and cardiovascular disease. However, there is no “magic number” hemoglobin A1c at which these complications are either guaranteed to occur or not occur. So, while “remission of diabetes” is a sexy term, in some ways it can be a hollow term, as it assumes that crossing the threshold from an HbA1c of 6.6% to 6.4% is going to make a real difference.
Also, we should not forget the short term risks of surgery compared to medical treatment. I’m not going to try to get into any statistical analyses, but there are real risks to these surgical procedures. In the Italian study, 10 out of 38 surgical patients had “late complications,” meaning things like incisional hernia, low albumin, osteoporosis, or iron-deficiency anemia. In the Cleveland Clinic study, 15/99 (15%) surgical patients compared to 4/43 (9%) of medical treatment patients had “serious adverse events requiring hospitalization.” Thus, with each patient considering one of these surgeries, we must weigh these risks against the benefits of the surgery. Is it better to take on these risks and aim for remission of diabetes? Or are you well-enough off going with medical therapy and avoiding the potential surgical risks? Somewhat remarkably, the intensive medical treatment groups saw their A1c drop around 1.5% in both of these trials, a none-too-shabby outcome. From my vantage point medical treatment versus surgery is an individualized decision that should be shared between patient and physician.
This is a rich subject matter and there is much more that could be said about these two papers. However, I generally try to be brief on this blog, so I’ll end here. Please share your thoughts.