The Surgeon’s Viewpoint: Swedish Obese Subjects Study and Bariatric Surgery

The Swedish Obese Subjects study is a fabulous example of how very-useful practical knowledge can come out of a well-conducted cohort study.  Not everything has to be a prospective randomized controlled trial!   This study has produced a number of landmark papers which provide convincing evidence that:

1.       Bariatric surgery offers survival benefit over the long term for the morbidly obese, despite the up-front mortality risk from the surgery itself.

2.       Bariatric surgery reduces cardiovascular and cancer deaths

3.       Bariatric surgery is durable: most patients do not regain the weight back

4.       Not all bariatric procedures are the same.  Some work better than others.

5.       Diets, behavioral modification, and “professional” weight loss coaching doesn’t really work for the morbidly obese in the long haul.

6.       And now….bariatric surgery prevents onset of diabetes!

The strength of the Swedish Obese Subjects trial is in the follow-up.  Since Sweden has a nationalized health care system, follow-up was completed on >95% of the initial cohort.  Such a trial could never be conducted in the United States….our people change jobs, towns, or insurances just way too often!

And there is just one more thing you should know about the Swedish Obese Subjects trial: the vast majority of the surgery cohort underwent vertical banded gastroplasty (VBG).  What’s that, you ask?  It was a first-generation bariatric operation that has been abandoned worldwide in favor of better (i.e. more effective) operations, such as gastric bypass and sleeve gastrectomy.  So if this trial were repeated in 2012, we would expect even better results in the surgical arm with fewer complications.

So where does that leave us?  For any patient with BMI > 40 (or BMI >35 with metabolic disease), you should really get them thinking about surgery as an option.  It’s not just about weight, and certainly has nothing to do with cosmetic appearance.  It’s about getting serious about treating metabolic disease: diabetes, hypertension, sleep apnea, hypercholesterolemia, PCOS, and others.  It’s about making sure that those diseases never develop in the first place.  It’s about reducing overall cancer risk, stroke risk, and heart attack risk.  And it’s about improving overall quality and quantity of life.

So why, then, with such powerful clinical evidence, do less than 1% of adults who would benefit from bariatric surgery actually get it?  That, my friend, is complicated, and probably worth another blog in its own right!

Jonathan Carter, MD

 

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Can bariatric surgery prevent diabetes?

I’ve previously written here about the 2 major New England Journal trials looking at treating type 2 diabetes with bariatric surgery.  Those studies showed a very robust ability of bariatric surgery to treat type 2 diabetes.  If you can use bariatric surgery to treat type 2 diabetes, what about prevention?  This question was examined in a more recent NEJM publication of selected results from the Swedish Obese Subjects (SoS) study from Carlsson et al.

Guest Post by Dr. Jonathan Carter

I’m pleased to say that my friend and colleague, Dr. Jonathan Carter, has agreed to follow this post with a guest blog post of his own, giving his analysis of the study.  Dr. Carter is an Assistant Professor of Surgery at UCSF, frequently performing bariatric surgery.

For those who skim blogs…

I’ll start with my take-away points, and then go backwards to analyze the study in more depth.  So, without further ado, the major takeaways from this study are:

1) Bariatric surgery impressively reduced the risk of type 2 diabetes in a middle-aged, obese population by 80% compared to the control group.  The number needed to treat (NNT) was 1.3!

2) This study did not address the most important comparison, i.e. between bariatric surgery and an intensive lifestyle modification program.  Unfortunately, the control group in this study received minimal attempt at lifestyle modification.  Prior studies like the Diabetes Prevention Program, the Finnish Diabetes Prevention Study, and the Chinese Diabetes Prevention Study showed between a 30-50% reduction in type 2 diabetes incidence with lifestyle modification.  However, one cannot directly compare the rates in these studies to each other.

3) Due to #s 1 and 2 above, the next study should directly compare bariatric surgery and intensive lifestyle modification with regard to diabetes prevention.

4) Weight loss prevents the onset of type 2 diabetes in obese patients.  Bariatric surgery causes weight loss.

With these results, we have to start discussing whether it is ethical, reasonable, and cost-effective to use bariatric surgery to prevent type 2 diabetes.

Now, for those of you interested in some more information about the study and results, keep reading…

Methods

This study was a prospective, non-randomized trial which enrolled 4,047 obese patients from 1987-2001 in Sweden.  The researchers note that they did not randomize the participants due to “ethical reasons related to the high postoperative mortality associated with bariatric surgery in the 1980s.”  In other words, enough people died from bariatric surgery at the time the study began that it would have been unethical for them to randomly assign people to have it done.

The control group was selected by a matching algorithm that concurrently tried to keep the current mean values of the matching variables between the two groups as similar as possible.  Included patients were aged 37-60 years old and had BMI over 34 for men and over 38 for women.  And, of course, they did not have diabetes at baseline.  Ultimately, those included in this analysis were 1,658 patients who had surgery and 1,771 who were in the control group.

Baseline characteristics: Surgery group had more severe risk factors

Due to the matching process, those in the surgery group were older, heavier (120 kg vs 114 kg), had higher insulin levels, higher blood pressures, worse cholesterol, higher smoking rates, lower physical activity rates, and higher caloric intakes compared to those in the control group.  Because the groups were non-randomized, it was likely that these “sicker” and “riskier” patients were more likely to be recommended surgery by their physicians.  However, in the end, this makes the results even more impressive because the surgical group had 80% lower rates of diabetes despite being a sicker group to begin with.  The surgical group had the decks stacked against them, and still came out ahead.  It is as if the surgical group started a 100 meter race with a 1-2 second handicap, but was still able to win.

No attempt at standardizing lifestyle therapy in control group

As I discussed above, a weakness of this study is that there was no attempt to standardize treatments in the control group.  Some might say that this is a positive because it reflects “real-world” treatments.  And indeed, the authors note that “patients in the control group received the customary treatment for obesity at their primary health care centers.”  However, according to questionnaires, this meant that only 54% of these patients received even some professional guidance.  So, nearly half of the control group received no help at all from their healthcare providers with weight loss.

The Results: Surgery caused weight loss and prevented diabetes

These two figures say it all… compared to “customary treatment” in this cohort of obese patients, the patients who got bariatric surgery lost significantly more weight (Figure S3) and had significantly less progression to type 2 diabetes (Figure 1A).

Is bariatric surgery really going to be the new standard for type 2 diabetes?

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.

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