1st World Congress on Interventional Therapies for Type 2 Diabetes

| November 10, 2008

by Liam J. Burns, MBA

Chief Operating Officer of the 1st World Congress and Partner at 3 Peaks Consulting, Mr. Burns has nearly 20 years experience in the healthcare industry. In addition to his work providing strategic consulting for emerging medical companies, Mr. Burns is also an executive coach helping organizations achieve breakthrough performance during periods of intense growth, change, and stress.

Introduction
The 1st World Congress on Interventional Therapies for Type 2 Diabetes was held on September 15–16, 2008, in New York to discuss the role of surgery and novel interventional therapies in the understanding and treatment of type 2 diabetes (T2DM).  Called the “largest gathering of diabetologists, bariatric surgeons, and public health leaders in history,” the Congress was attended by nearly 1,000 medical professionals from 46 countries around the world. The distinguished faculty included over 80 world renowned experts in virtually every aspect of diabetes, obesity, surgery, nutrition, and health policy. The Congress created a unique forum where medical and surgical experts explored the critical issues surrounding this treatment option directly with health policy leaders. Demonstrating the global interest in this promising new field of medicine, the Congress was endorsed by 26 of the most prestigious diabetes, medical, and surgical societies, including the American Association of Clinical Endocrinologists (AACE), the European Association for the Study of Diabetes (EASD), the International Diabetes Federation (IDF), the International Federation for the Surgery of Obesity and Metabolic Disorders (IFSO), the Obesity Society (TOS), and many others. This article summarizes portions of the Congress for Bariatric Times readers.

Francesco Rubino, MD (Director of the Diabetes Surgery Center at Weill Cornell Medical College) chaired the two-day Congress and invited the urgent collaborative efforts of faculty and attendees to address the broadening global impact of T2DM. The format of the Congress was uniquely structured to ensure lively multidisciplinary discussion on each topic. Sessions began with keynote lectures providing a comprehensive review of published and unpublished data, while the majority of time was allocated to intensive discussion by faculty panels composed of experts with widely differing views.

Opening Ceremonies

The Congress, hosted by Weill Cornell Medical College and NewYork-Presbyterian Hospital, opened with Fabrizio Michelassi, MD (Professor and Chairman of Surgery) welcoming attendees on behalf of Weill Cornell Medical College, one of the first academic medical programs dedicated to the surgical treatment of T2DM. Antonio Gotto, MD, DPhil (Dean and Provost, Weill Cornell Medical College), a cardiologist by training, in his welcoming remarks stressed how closely diabetes and cardiovascular disease are entwined. Herbert Pardes, MD (CEO, NewYork-Presbyterian Hospital) emphasized that the Congress represented “possibilities and progress” that are desperately needed, estimating that 25 percent of inpatients at NewYork Presbyterian hospital have diabetes or are being treated for diabetes-related complications. Richard Daines, MD (New York State Health Commissioner) gave the keynote address, drawing a lesson from recent Wall Street woes. “If we put off facing problems and let them build up long enough, then they lead to catastrophe and desperate attempts to bail out.” He expressed hope that the Congress would represent a very forward-thinking approach to the problem of diabetes, especially given the disproportionate impact the disease has on minority populations.

Jose Cordova Villalobos, MD (Minister of Health of Mexico), a surgeon himself, brought a sense of urgency to the audience, sharing staggering statistics on the growth of diabetes and obesity that have made diabetes the number one cause of death in Mexico, ahead of cardiovascular disease. Excited about the new possibility of surgery complementing other treatments in the fight against diabetes, Dr. Cordova declared the Congress open.

Francesco Rubino, MD (Congress Director and bariatric surgeon) began his opening remarks by reminding the audience that diabetes currently affects 246 million people, including 24 million Americans—numbers that are growing at epidemic rates worldwide. These numbers represent a global health crisis and an enormous burden on national economies. He said that finding new approaches to understand and treat diabetes has become a “race against time.”

Rubino summarized clinical data showing that T2DM can be forced into remission after several types of bariatric procedures. Remission was defined as the ability to normalize glycemia and discontinue diabetes-related medications. He stated, “This is an extraordinary phenomenon, especially if you think that diabetes is rarely forced into remission and when it is, it requires continuous effort. By contrast, surgery is offering the promise of durable remission through a single procedure, which is something that we have not seen in the history of diabetes.” This evidence should lead us to challenge the current definition of diabetes as a chronic, progressive, and irreversible disease and ask: For the first time, can we go beyond managing and aim for a cure for diabetes in our lifetime?

With a 92-percent reduction in diabetes-specific mortality achieved through bariatric surgery, and only one percent of patients with a body mass index (BMI)>40kg/m2 having access to bariatric surgery, Rubino raised the use of surgery to treat diabetes as a public health issue. This data showed that “despite surgery having the potential for improving life expectancy in patients with diabetes, we are actually not offering this option often enough to our patients.” He added caution to this statement by saying, “However, we don’t have enough knowledge yet to clearly identify the ideal candidate patients,” stressing the need for further clinical  investigations.

Rubino also pointed out the opportunity that surgery offers to better understand the disease. He speculated that the gastrointestinal tract may harbor potential mechanisms that contribute to the development of diabetes. “Studying the mechanisms of action of gastrointestinal (GI) surgical procedures may lead to important discoveries on the origin of diabetes and pave the way to future interventional and pharmacological therapies.”

Session I: Epidemiology, Pathophysiology, and Socioeconomic Burden

Session 1 focused on defining diabetes, environmental factors driving its growth, and the socioeconomic burden it creates. Paul Zimmet, MD, PhD (endocrinologist) opened the session with a witty but pointed overview acknowledging that diabetes in combination with obesity is the biggest health problem facing humanity. “What AIDS was in the last 20 years, diabetes and obesity will be in the next 20 years,” adding that the aptly named diabesity epidemic is also driving a resurgence of cardiovascular disease. Takashi Kadowaki, PhD, MD (endocrinologist) provided a perspective from Japan where diabetes has exploded in recent years despite what is believed to be a genetically decreased susceptibility to obesity. Both environmental (i.e., high-fat diet, sedentariness) and genetic factors (higher diabetes incidence at lower BMI levels) were identified as the leading causes, demonstrating that there are a variety of etiologies for diabetes besides just the “westernization” of various cultures.

George Alberti, MD (endocrinologist) reviewed the historical evolution of the limits for defining type two diabetes (T2DM), impaired glucose tolerance (IGT), and impaired fasting glucose (IFG) that were originally developed based on an increased risk of retinopathy and macroangiopathy. Based on new studies that confirm these risks occur at much lower levels, he suggested that the limits be set at “any level at which you are getting an abnormal physiological response.” For T2DM, this would include IGT and IFG. In reviewing the criteria for obesity and metabolic syndrome, he suggested that waist-girth measurement or alternatively waist-hip ratio may be more effective than BMI as 1 of the 5 key screening parameters. He highlighted the dramatic relationship between obesity and the risk of developing T2DM with data showing that women have an eight-fold increase in risk of T2DM even within healthy BMI levels (<22–25kg/m2).

It is estimated that 10 percent of US healthcare costs are directly related to diabetes while an even greater percentage of spending is on complications from diabetes. Shlomo Ben Haim, MD, DsC (cardiologist) reviewed the staggering socioeconomic burden, citing that the US will spend $6.6 trillion over the next 30 years on the treatment of diabetes complications. What’s worse, a reduction in the US workforce due to diabetes will cause productivity losses that could stagnate the economy. Known to have a disproportionate effect on lower socioeconomic groups, he described a “poverty spiral” where low-cost unhealthy foods are purchased over healthier alternatives, resulting in higher diabetes-related absenteeism, disability, mortality, and further poverty.

Panel Discussion I
With the Federal Reserve just having announced its $85 billion bailout of AIG, and the $700 billion bailout of the US financial system looming on the horizon, faculty panel members stated that diabetes needs a bailout before it bankrupts entire countries. “Diabetes is the only chronic disease that has not seen a decrease in the last 20 years,” stated Gojka Roglic, MD, diabetologist and epidemiologist for the World Health Organization (WHO), while several members of the panel agreed that the current projections of incidence and treatment costs were conservative.

In terms of treatment options, there was strong consensus that lifestyle changes and primary prevention programs are not enough to battle the disease. Others called for earlier intervention and emphasized the need to gain control of the disease quickly after onset. Bernard Zinman, MD (endocrinologist) highlighted that the Canadian national diabetes strategy includes traditional treatment methods as well as bariatric surgery. The session concluded with the entire panel calling for more effective ways to treat the disease, additional research, and large global clinical trials, as it was acknowledged that half a billion people around the globe require immediate treatment.

Session II: Conventional Diabetes Therapies—Outcomes and Limitations
John Buse, MD, PhD (endocrinologist) began the second session by reviewing the positive aspects of current and soon-to-be available pharmacologic therapies by stating that there were over 10 different studies, with more on the horizon, that show diabetes can be prevented or delayed through current medical therapies and lifestyle change. In particular, he highlighted the NHANES study, which showed the proportion of the diabetic population in the US achieving an A1C level of less than seven percent has increased to 55 percent.1 Earlier diagnosis, the wide assortment of therapeutic alternatives, and more powerful glucose-lowering drugs were cited as the key factors driving this improvement. Buse also reviewed the results of the DURATION 1 trial soon to be published in Lancet, which demonstrated that new antihyperglycemic agents, specifically incretin agonists with greater than 24-hour coverage like exenatide, provide “exceptional glucose management with weight loss.”

The downside of current therapies were presented by Stephanie Amiel, MD (endocrinologist) who started by reviewing a prospective diabetes study in the United Kingdom (UKPDS),2 which showed that even with treatment, life expectancy for people with T2DM was lower across all age groups. She stated that medical therapies are helping achieve glycemic targets, but cautioned that the levels are not set low enough to prevent micro- and macrovascular problems, while side effects such as weight gain3 are linked to further increases in cardiovascular risk. Side effects, including hypoglycemia, weight gain, anemia, and other metabolic complications, also have a strong impact on patient adherence to therapy. Interestingly, physician compliance is a problem as well. In a study4 at the Kaiser Permanente Hospital System, 30 percent of patients were affected by physicians not appropriately intensifying T2DM therapy. She concluded that while data supports the goal of normoglycemia, some patients never achieve this due to limitations of current medications and the failure to prescribe them. Emphasizing that patient and physician behaviors affect the success of any therapy, she asked the audience: Are we setting ourselves up for failure by waiting for the patient to deteriorate prior to starting intensive therapy?

In the surgical management of T2DM, Henry Buchwald, MD (surgeon) reviewed a new meta-analysis of 621 independent studies about to be published in the American Journal of Medicine, where marked weight loss across the four primary bariatric operations was shown and reduction or complete resolution of T2DM and other comorbidities of obesity were demonstrated to last beyond two years. These results were contrasted with a major study of medical management of T2DM, in which an increased mortality rate even with intensive therapy was found.5 It was suggested that medical therapy, though intuitively regarded as less risky than surgery, may not be less risky given the long-term, potentially life-threatening consequences of both T2DM and conventional treatment methods.

Panel Discussion II

The panel began by briefly discussing the need to implement social and environmental change to support lifestyle modification, then explored surgical interventions and hybrid therapies, with a spirited discussion of the ACCORD study woven throughout. Allison Goldfine, MD (endocrinologist) commented that there are major well-controlled studies demonstrating that bariatric surgery improves cardiovascular and other survival rates, although the long-term disadvantages of surgery are less clear at this point. Goldfine identified a growing recognition of a higher-risk group of T2DM patients who will benefit from bariatric surgery due to the significant changes caused in the gastrointestinal hormones following surgery, and, therefore, the possible regeneration of beta cells in the pancreas and resulting improvement of T2DM. Jeffrey Mechanick, MD (endocrinologist) acknowledged the “compelling” numbers showing the benefit of surgical intervention, but cautioned that these patients should receive lifetime followup by experts who can anticipate nutritional and metabolic complications unique to surgical patients.

John Buse, MD, PhD, commented, “I think we need new surgical and medical approaches that take into consideration the underlying physiology without restricting the patient’s ability to enjoy a holiday meal with family, as patients see this as an unacceptable lifestyle choice.” It was generally agreed by the panel that the future of T2DM treatment lies beyond purely surgical intervention in hybrid therapies that represent knowledge acquired through medical and surgical approaches. Luc Van Gaal, MD, PhD (endocrinologist) added that regardless of the approach, in both medical and surgical treatments, evidence indicates the importance of initiating therapy soon after the diagnosis of diabetes is made.

Session III: Bariatric Surgery—Diabetes and Metabolic Outcomes
This session, sponsored by the ASMBS, reviewed the successes and limitations of bariatric surgery as a therapy for T2DM. Philip Schauer, MD (surgeon) presented the latest clinical evidence on bariatric surgery, categorizing the data according to the type of clinical trial. He began with 13 retrospective studies that all showed a relatively high degree of resolution or improvement in T2DM. Emphasizing that controlling T2DM through gastric bypass is not just about glycemic control, he reviewed a study from the Annals of Surgery that demonstrated an improvement in the triple endpoints of HbA1C, hypertension, and hypertriglyceridemia as well.6

The Swedish Obesity Subjects (SOS) study7  was presented next as the longest-running study on weight loss and resolution of comorbidities of obesity, including T2DM. With unprecedented 99-percent followup, Schauer presented 10-year data of this prospective, matched, controlled study where the control group was matched based on 14 key factors. The study demonstrated that the surgery group had a dramatic decrease in HbA1C and fasting plasma glucose (FPG), while the control group increased over that time. In addition, the surgery group had a significant decrease of new onset diabetes as well. Comparison within surgical procedures suggested that RYGP has the greatest impact on excess weight loss, HbA1c, and FPG.

Schauer acknowledged the limited number of prospective, controlled, randomized trials, highlighting a study led by John Dixon8 that compared the impact of gastric banding (Lap-Band, Allergan, Inc.) with medical management and lifestyle changes to medical management and lifestyle changes alone on T2DM. At two years, the study showed good results with remission (defined as HbA1c<6) at 73 percent for the Lap-Band versus 13 percent for medical management alone and weight loss of 20.7 percent versus 1.7 percent.

The updated results of the Buchwald meta-analysis from the previous session were reviewed again, followed by a review of two studies that indicated the predictors of diabetes resolution after bariatric surgery were pre-operative severity of diabetes (% of patients using insulin), duration of diabetes, BMI and preoperative HbA1c levels.9,10 Schauer highlighted the current ADA/EASD treatment algorithm, which does not include bariatric surgery, but reviewed the most recent statement by the ADA stating that surgery “may be considered for some individuals with type 2 diabetes and BMI>35kg/m2 and can result in marked improvements in glycemia.” The ADA statement had no mention of patients with BMI<35kg/m2 but did acknowledge that long-term studies of bariatric surgery were ongoing. At the end of his presentation, Schauer concluded that based on the extensive studies presented, surgical intervention provides effective control of T2DM but called for randomized, controlled trials that would compare surgery to medical management.

Bruce Wolfe, MD (surgeon) presented data on the morbidity and mortality of bariatric surgery. He showed that mortality has declined from 0.89 percent in 1998 to 0.19 percent in 2004, a reduction of 79 percent according to the Agency for Healthcare Research and Quality (AHRQ) database, the largest administrative health care database in the US.11 He also presented statistics from the California Patient Discharge data (1995–2004) that showed 30-day mortality at 0.33 percent.12 These findings were consistent with ASMBS most recent 12-month data in 235 Centers of Excellence, which showed a 30-day mortality rate of 0.31 percent and a 90-day mortality rate of 0.38 percent.13 Wolfe believes the mortality associated with bariatric surgery has significantly improved over the last five years due to improvements in medical devices and the establishment and expansion during this period of the ASMBS Center of Excellence (COE) program with mandated parameters of care and mandatory outcomes reporting, including all deaths.

Ted Adams, PhD, MPH (UT), a cardiovascular geneticist, remarked on the attainment of weight loss, longer life, and better overall health now associated with bariatric surgery. Eight comparative studies showed that after bariatric surgery, overall mortality was lowered by 29 percent to 89 percent depending on the study that “covered the gamut of different bariatric surgery options.” Adams’ own study showed a 92-percent reduction in diabetes-related deaths (8,000 patients followed for a mean of 7 years).14 In addition, Adams shared unpublished data that compared three groups (gastric bypass, seeking gastric bypass—denied surgery, control) that showed dramatic and statistically significant improvement in resolution of T2DM and weight loss from gastric bypass, as well as improvement in many other comorbidities, including hypertension, insulin usage, triglycerides, HDL/LDL, and systolic blood pressure.

Panel Discussion III
Phil Schauer began by asking each panel member to share his or her perspective on the strength of the evidence reviewed during the session and the potential role of bariatric surgery in treating diabetic patients who are morbidly obese. Allison Goldfine, MD (endocrinologist) started by saying that bariatric surgery appears to have substantial benefits but, like many of the endocrinologists on the panel, she wanted to see longer-term studies similar to that seen in pharmaceutical trials. John Dixon, MD (surgeon) countered that he “did not know of a better treatment for people with diabetes than losing weight,” with Mario Morino, MD (surgeon) adding that there is “no doubt these patients should have surgery; it’s already proven.” John Buse, MD (endocrinologist) stated that bariatric surgery should be “considered” as a treatment option for diabetes, but he and others on the panel agreed that a different level of evidence was needed before changing clinical practice.

This focused the discussion on the type of clinical evidence necessary and the parameters of the ideal trial, which Harold Lebovitz, MD (endocrinologist) described as a randomized, controlled trial of a diabetic population with surgery and best medical treatment/lifestyle groups, demonstrating lower complications, including reduced mortality and cardiovascular events and at least 10-year follow-up. Xavier Pi Sunyer, MD MPH (endocrinologist) and others added the need to better understand nutritional issues and bone problems after surgery, while Antonio Gotto, MD, DPhil (cardiologist) commented that lipid changes should also be researched, as reductions in LDL were significantly higher with surgical weight loss when compared to nonsurgical weight loss (20% vs. 5–6%).

In the end, the panelists agreed that longer-term, randomized, controlled trials were needed, and Schauer called on all of the panel members to lobby the National Institutes of Health and payors to support a multicenter trial with our best scientists.

Session IV: Bariatric Surgery to Treat Diabetes in PatientS with BMI<35kg/m2
This session focused on the potential for utilizing surgery to treat diabetic patients who are not severely obese (BMI<35). In his keynote lecture, Francesco Rubino, MD (surgeon) stated that the only randomized, clinical trial to date that has compared surgery (Lap-Band) to medical therapy in patients with BMI below 35 kg/m2 is the Dixon study.8 This study demonstrated that surgery was superior to conventional medical therapy with lifestyle changes for both weight loss and remission of diabetes at two years. Rubino went on to suggest that much can be learned about the metabolic effects of bariatric surgery through a review of clinical and preclinical data from procedures that are similar to gastric bypass. His early research in rats focused on whether the effects of surgery on diabetes were due to just caloric restriction and weight loss alone or if there was an anti-diabetic mechanism directly resulting from the change in gastrointestinal anatomy. Using a modified RYGB, which reproduces the characteristic bypass of duodenum and jejunum but maintains the stomach intact, he found that lean animals with T2DM had the same positive effects on their diabetes as obese ones, concluding that the improvement of diabetes was not due to weight loss alone.15

Three different studies16-18 in humans confirmed Rubino’s animal findings that changing the anatomy of the bowel stimulates resolution of T2DM in BMI<35kg/m2. The first study,16 led by Ricardo Cohen, used a duodenojejunal bypass (DJB) in nonobese patients with diabetes. At one year followup, most of Cohen’s patients have normal HbA1c levels even without significant weight loss. The second study,17 an ongoing trial led by Aureo de Paula, compared ileal interposition with sleeve gastrectomy to ileal interposition with diverted sleeve gastrectomy alone in patients with BMI<35kg/m2. In this study, 86.9 percent of patients achieved adequate glycemic control (HA1c<7%) without antidiabetic medications as well as normalization of plasma cholesterol, hypertension, and triglycerides, again suggesting that changing the anatomy of the bowel stimulates a number of metabolic changes—not just resolution of hyperglycemia. Further evidence for the antidiabetic effect of anatomic changes to the GI tract comes from a randomized, controlled trial18 comparing laparoscopic sleeve gastrectomy (LSG) to laparoscopic sleeved gastric bypass (LSGP) with exclusion of the upper small bowel in patients with uncontrolled T2DM and BMI<35kg/m2. This data by Wei-Jei Lee presented at the latest ASMBS meeting showed no difference in weight loss between the two groups after six months.18 However, 60 percent of patients in LSGB group had successfully achieved the endpoint treatment goals (HA1c<7%, LDL<130mg/dl, and triglycerides<150mg/dl) versus 14 percent of patients in the LSG group, suggesting that bypass procedures may be more effective on metabolic syndrome than restrictive procedures alone.

Rubino stated that it may be a reasonable concern that using conventional bariatric operations in patients with lower BMI levels may cause excessive weight loss. However, in reviewing his preclinical work, it was demonstrated that gastric bypass had no effect on food intake or body weight in nonobese rats while driving diabetes into remission.19 This animal data is consistent with that seen in humans in partial gastric resection with bypass of the duodenum and jejunum. Rubino quoted a clinical study showing that these procedures did not induce excess weight loss in patients who are not obese (preoperative BMI in this patient population was under 25kg/m2), suggesting that the complication of excess weight loss may not be a serious concern after gastrointestinal bypass procedures in patients with BMI<35kg/m2.20

To understand the number of patients around the world who have had surgery with BMI<35kg/m2, the Diabetes Surgery Center at Cornell and IFSO launched a survey in August 2008. In the first month, data on 237 patients were received, with a majority receiving gastric bypass. Dr. Rubino cautioned that this was not a clinical study, indicating the data showed all procedures (BPD, DJB, GB, GBP, SG) helped hyperglycemia while the bypass-type procedures had a greater impact on HbA1C, similar to what has been observed for morbidly obese patients. In addition, the survey showed reduced medication usage, with many patients able to suspend medications completely. Rubino added, “This information suggests that surgery, whatever operation you choose, does not stop working at BMI of 35kg/m2.”

In conclusion, Rubino stated that while we do not have all the answers we need at this time, in his opinion there is enough information to support that the BMI cutoff of 35kg/m2 is not a reliable indicator to distinguish between patients who would improve their glycemic and metabolic control from surgery and those who would not.

Panel Discussion IV
Bernard Zinman, MD (endocrinologist) opened the panel stating, “You don’t always need a randomized, controlled trial to draw a conclusion.” The best example of this is the link between smoking and cardiovascular disease, in which there is a vast amount of evidence that supports the link but no randomized, controlled trial. “I would argue that in patients with BMI>40kg/m2 with other comorbidities, we don’t need a randomized, controlled trial to know that gastric bypass will have great outcomes.” He added, “In patients with BMI<35kg/m2 who can be managed medically, there is biological plausibility that surgery works, but we will need a randomized, clinical trial before recommending surgery.”

After his opening comments, Zinman asked the panel the following question: If BMI is not a reliable index for the surgical treatment of diabetes, what should be used to determine if surgery is appropriate? Desmond Johnston, PhD (endocrinologist) suggested that because surgery is focused on reducing the complications of diabetes, and in particular the cardiovascular risk, we should be utilizing an appropriate cardiovascular risk engine score that measures the risk factors that we are not managing well. Ross Brechner, MD, (Lead Medical Officer, Centers for Medicare and Medicaid [CMS]) cited the extensive clinical data that already exists utilizing BMI and the lack of existence of another single factor. Several members of the panel agreed that BMI was one reliable factor indicating risk, but their comments emphasized that BMI should not be the only risk factor used. John Dixon (bariatric surgeon) asserted, “Diabetes risks increase dramatically well below a BMI of 35kg/m2, so why wait until the BMI gets higher before doing something?” Ricardo Cohen (bariatric surgeon) added, “If you are saying to use surgery only when medical therapies fail, it’s too late because beta cell function is dead. You need to perform surgery before this happens.”

Rubino emphasized that he did not believe surgery should be the first line of therapy for diabetes, but that it should be considered as a second or third option, when other treatments are not working. Surgery is never the first option for treatment of any illness, but when the risks and benefits of surgery make it appropriate, the patient is then given the option to decide between available therapies. However, to deny a patient currently under medical management with all the cardiovascular risk factors predicting a poor prognosis over the next 5 to 10 years the option of surgery just because BMI is 34kg/m2 would be “discriminatory.” Takashi Kadawaki, PhD, MD (endocrinologist) stated, “In Japan, we are very keen to reduce body weight in diabetic patients because a BMI of 35kg/m2 in the Asian population is similar to a BMI of 40kg/m2 in Caucasians. He expressed concern that patients seemed to receive medical management therapies from endocrinologists and surgical treatment from surgeons, stating that the best care for the patient is determined through agreement between internists and surgeons.

At one point, Dr. Brechner asked, “Why hasn’t everyone gotten together to do a multicenter, multicountry trial already?” Zinman responded that a meeting like the World Congress was necessary to make this happen, suggesting that the trial should take patients where best medical management has failed and randomize them to surgery or continued intensive therapy. Walter Pories, MD (bariatric surgeon) called on insurance carriers who “have the most to gain” to support these trials.

Session IX: Consensus Guidelines from the Rome Diabetes Surgery Summit (DSS)
Sponsored by the International Diabetes Surgery Task Force (IDSTF), this session included a brief introduction of the IDSTF goals and its
members.

Lee Kaplan, MD (endocrinologist) briefly reviewed the development process for the 1991 National Institutes of Health (NIH) Guidelines for Bariatric Surgery, which are currently used by reimbursement organizations. Interestingly, a statement posted with the NIH guidelines emphasizes that they are more than five years old and “likely to be out of date and, at worst, simply wrong,” acknowledging the advancements in medical research and knowledge since they were written.

It was generally agreed that 17 years after the initial NIH Guidelines for Bariatric Surgery were established, a new document representing developments of the field inclusive of the metabolic effects of bariatric surgery would be valuable to the health community. David Cummings, MD (endocrinologist) reviewed the findings of the DSS after defining the structure and processes used last year to gain consensus. The voting faculty of 52 was primarily academic- and university-based (93%), made up of 60 percent non-surgeons and 40 percent surgeons, and included no one primarily employed by industry. Consensus (defined as a 2/3 majority) was reached through an iterative process in real time with the language of each statement adjusted until the group reached agreement. A draft of the DSS consensus statement was recently submitted for publication and a summary of it was presented during this session. A variety of relevant diabetes and surgical organizations were provided with an advance copy of the DSS draft statement as well as supporting scientific evidence for the recommendations and were asked to nominate a representative for the panel discussion at the World Congress.

Panel Discussion IX
The opinion of the faculty and audience at large was captured using an audience polling system. The audience and faculty strongly agreed that any guidelines for the surgical treatment of diabetes should be developed by a multidisciplinary group to ensure credibility and wide adoption. They also strongly agreed that the creation of multiple guidelines by different organizations would be harmful to patients and providers. Schauer then opened the discussion of the DSS consensus statement up to the panel. Leading up to the Congress, the following organizations were given a copy of the DSS statement: AACE, ADA, ASMBS, Diabetes UK, and TOS.

Scott Shikora, MD (President of ASMBS) announced that the executive council of the ASMBS wholeheartedly “endorsed the consensus statement as is,” while welcoming continued discourse and research as a constructive part of development. Rubino stated that the discussions emphasize that “we are at the very beginning of this discipline” and that no statement says “exactly what you should do in a certain situation.” We have enough knowledge today to make the recommendation for surgery when other treatments are not working. He added that over time the recommendations and guidelines will get more specific as additional data become available.

Caroline Apovian, MD, expressed a positive initial reaction to the DSS consensus statement on behalf of TOS, stating, however, that their review process was not yet complete. Jeffrey Mechanick, MD, speaking on behalf of the AACE, emphasized that AACE had already fully endorsed and supported the DSS call for further research. He added that AACE continues to review the DSS document and the remaining recommendations. The other society representatives stated the review process was ongoing and that their societies were committed to complete the review process before the end of the year.

Several panelists emphasized the importance of understanding the mechanism of action of surgery. Dr. Cummings agreed but noted how often in medicine “one doesn’t wait to understand a mechanism of action before advocating the clinical use of something that is proven effective.” He cited the case of metformin, where clinical use was started before its mechanism of action was fully understood. “You may say we need more clinical evidence, but I am not sure we need to understand the mechanism beyond a biologic plausibility, which certainly seems self-evident in this case.” Many other panel members also expressed the need for additional clinical research, which led Dr. Pories to emphasize the meaningful and significant data that could come from payors as they “have more data than all of us.”

The session concluded with George Alberti and Paul Zimmet complementing Francesco Rubino on his leadership in organizing the DSS and the World Congress, bringing the global health community together in a collaborative effort against diabetes.

Session X: The Economics of Interventional Therapies and Implications for Public Health
This session focused on a study led by Pierre Cremieux, PhD, MA, a leading health economist, which analyzed the cost-effectiveness of bariatric surgery for treating morbid obesity (Please see page 32 for the Bariatric Times 5 Minutes With interview on this economic study). Cremieux presented data from the study that identified the break-even point for bariatric surgery used to treat the morbidly obese patient with diabetes. The study utilized a large claims database that matched surgery patients with non-surgical patients with similar comorbidities. The data revealed that bariatric surgery for a morbidly obese patient with diabetes pays for itself in 35 or 41 months. Cremieux stated that the faster return on investment (ROI) reflects more recent data from 2003 to 2006, which coincides with the advent and growth of the Bariatric Centers of Excellence. He went on to say, “This is the first time I have done a study with an ROI greater than one; it just doesn’t happen.”

Panel Discussion X
David Flum, MD, MPH (surgeon) commented that the US and many other countries face a vast public health crisis in terms of obesity and diabetes that shows “no sign of cresting.” It was widely acknowledged that there was great health and financial benefit associated with expenditures on bariatric surgery for obesity and diabetes. Adrian Pollitt, Head of the National Health Service in the United Kingdom, agreed with Cremieux’s findings, stating that the cost-efficiency of the operation is not in doubt and evidence from National Institute for Clinical Excellence (NICE) confirms it. He added that BMI might not be the key determinant factor based on the costs/benefits of other comorbidities. The panel agreed that the up-front investment required to cover surgery for every patient is a serious challenge to every healthcare system—both in obtaining the financial resources and allocating them to the right patients.

Charles Stemple, Medical Director from Humana, stated that despite the current estimate of $13,000 to $15,000 in annual treatment costs for diabetic patients, there were two issues in achieving broad coverage of bariatric surgery for treating diabetes. Patient turnover between insurance companies creates disincentives for a single insurer to cover the surgery unless all insurance companies have similar coverage. In addition, employers who bear most of the costs of care and would have to cover the upfront costs want to see more data to ensure that they can capture that ROI in 2 to 3 years for retained employees.

The Congress as a body was convinced of the need for additional research on ROI as well as dedicated investigation into finding the financial means to extend medical and surgical treatments to patients suffering from T2DM and obesity.

Other Sessions
The Congress also covered a session on the mechanisms of surgical control of diabetes and their implications for novel pharmaceutical and interventional therapies by Dr. Cummings, the highlights of which will be featured in an upcoming issue of Bariatric Times. Other sessions included novel interventional therapies, obesity and diabetes in adolescents, and research priorities. The Congress concluded with a session that provided a personal look into the perspectives of several T2DM patients, some of whom had received conventional T2DM therapy and others who elected to have bariatric surgery. The complete proceedings of the Congress will be available in the near future on DVD.

What is Covidien’s role in metabolic surgery?
Due to the sheer magnitude of the global diabetes epidemic and the devastating effects of this disease, being able to offer total resolution to diabetes sufferers is a top priority. Covidien is leading the way in supporting basic science and clinical research and investing heavily in the development of innovative technologies with the ultimate goal of resolving T2DM and other metabolic comorbidities. These initiatives give new purpose to the entire surgical community to propel bariatric surgery beyond being just weight loss surgery, expanding surgical practices and positively impacting patients and families worldwide. We know that collaboration with medical professionals and the bariatric community is essential to identifying new treatment options for this patient population. We also want patients to be fully informed of the impact that bariatric surgery can have on their diabetes and have recently launched www.bariatrics4diabetes.com with this in mind.

Given the critical role pharmaceuticals play in managing diabetes, as a medical device company, how are you going to integrate medical management into interventional therapies?
First, I believe that medical management will always play an important role in treating diabetes and other metabolic disorders. To understand the underlying mechanism of how bariatric surgery drives diabetes into remission, Covidien is partnering with world-renowned scientists, physicians, and surgeons to conduct ground-breaking multidisciplinary research. We believe gaining insight from a variety of medical and surgical perspectives will be the most efficient way to advance interventional therapies, as well as to understand their place in a broad spectrum of treatment options. Together with their caregiver, a fully informed patient should be able to select the treatment that is right for him- or herself after weighing the advantages and risks of each option.

How will the emergence of single port surgery and NOTES have an impact on the development of metabolic surgery?
It’s clear that both the medical community and individuals suffering from metabolic disorders desire treatment options that are both lower in risk and less invasive than surgical procedures that are offered today. While the morbidity and mortality rates of bariatric surgery have dramatically improved over the past few years, it is our understanding that a significant population of patients that would benefit greatly from bariatric surgery are still hesitant to undergo these procedures. We believe SILS™ procedures and NOTES™ techniques, as well as a variety of associated technologies, have the potential to offer less invasive options that may also offer a lower-risk profile for patients.

Diabetes and obesity is now considered a global epidemic, with much of the growth occurring outside of the US. What is Covidien’s plan for reaching these patients?
We fundamentally understand that diabetes and metabolic syndrome presents itself differently within various ethnic populations around the world. This may provide researchers with additional clues to the etiology of the disease. It also suggests that treatment methods may have to be adjusted for ethnic differences. Our ongoing collaborative efforts with medical and surgical leaders are worldwide in scope, allowing us to orient our scientific and product development projects accordingly. Ultimately, Covidien is well positioned to bring new technologies to markets around the globe.
Interview with GI Dynamics

GI Dynamics has developed one of the first less invasive technologies for obesity and T2DM. How is this technology different from existing surgical approaches? How will this product prevent long-term weight regain?
GI Dynamics has developed the EndoBarrier™ Gastrointestinal Liner, as a noninvasive, orally delivered, removable device that lines a portion of the small intestine, resulting in substantial weight loss and improved glycemic control. Early clinical data have shown that the EndoBarrier™ provides both weight loss and immediate resolution of T2DM.

Due to the invasive nature of bariatric surgery, many patients decide to have surgery only as a last resort after reaching higher BMI levels when they are experiencing the effects of obesity-related comorbidities such as diabetes. EndoBarrier’s™ noninvasive implantation does not require permanent alteration of the anatomy, which means that patients may consider this treatment at an earlier stage in their disease progression.

The EndoBarrier™ is designed to help patients lose a substantial amount of weight and maintain weight loss while the device is in place. The current design has been studied in clinical trials as long as 11 months. Additional clinical trials are ongoing to evaluate the longer-term clinical benefits of EndoBarrier™ in both obese patients and those with T2DM. We are currently engineering and testing new designs that will enable the device to last for extended periods of time as well as studying serial devices, which would be implanted and removed as needed over the course of a patient’s life. Eventually, the EndoBarrier™ may have the potential to remain implanted for life.

In any case, whether a patient chooses a surgical or nonsurgical obesity treatment, the best results are achieved when the patient receives comprehensive support to maintain long-term weight loss, including healthy lifestyle habits, such as diet and exercise.

With conventional bariatric surgery, the creation of the stomach pouch provides satiety feedback to help patients limit their food intake. How will the EndoBarrier™ impact satiety?
The EndoBarrier™ has similar biofeedback mechanisms to that which is experienced with bariatric surgery. It is designed so that a patient will feel full longer and have the urge to eat less. If a patient implanted with the EndoBarrier™ gastrointestinal liner were to overeat, the patient may experience discomfort similar to that of other bariatric surgical procedures. GI Dynamics is continuing to study whether this biofeedback is mechanical, hormonal, or a combination of both.

How will the EndoBarrier™ be used with existing medical therapies and technologies?
We are continuing to determine how EndoBarrier™ is best integrated with current treatment options for diabetes and obesity. For example, based on positive data from clinical trials in patients with T2DM, our advisory board (including gastroenterologists, endocrinologists, and bariatric surgeons) believes that one therapeutic strategy may be to use the EndoBarrier™ for six months to achieve rapid glucose control, help patients lose weight, and get them off medications that are leading to weight gain. Once the diabetes is under control, a physician would recommend a program to the patient that could potentially include drugs and combination therapies to maintain results. If necessary, products such as continuous glucose monitoring could be used to help titrate the optimum dosing of medications.

Who will be performing the implantation? Will the EndoBarrier™ ever become a product that can be implanted in a doctor’s office?
We believe the physician performing the implantation should be a gastroenterologist or surgeon with appropriate training in current endoscopic techniques. During clinical trials, implantation has been performed in an endoscopy suite or operating room in approximately 30 minutes. Initially, general anesthesia was used in all patients, but we are now using conscious sedation for some patients. In the future, we believe this will enable the procedure to be performed in any endoscopy suite.

Regardless of who implants the device, we see our technology as part of the evolution of bariatric centers into a new “metabolic center of excellence,” which includes specialists in nutrition, behavioral modification, pharmacologic therapy, endocrinology, gastroenterology, and surgery.

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Acknowledgment
The author would like to acknowledge Richard Lobell Photography for the images that appear in this article.

Category: Past Articles, Symposium Synopsis

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