Obesity Week 2016

October 31 – November 4; New Orleans, LA; Full Report – Draft

Executive Highlights

This report features our full coverage of the 2016 Obesity Week meeting held in New Orleans. Co-sponsored by The Obesity Society (TOS) and the American Society for Metabolic and Bariatric Surgery (ASMBS), this conference provided us with a wealth of new insight on a range of topics in obesity. From an evaluation on the effect of the Berkeley sugar-sweetened beverage tax to results of the long-awaited ACTION study, we soaked up both sun and smarts at this fascinating conference.

Below we share our detailed discussion and commentary from this full week of learning and are organized into the following seven themes: (i) medical obesity therapies; (ii) policy; (iii) lifestyle intervention; (iv) additional topics; (v) corporate symposia; (vi) posters; and (vii) exhibit hall.  Talk titles highlighted in yellow were some of our favorites from the meeting, reflecting what we found to be most notable. Talk titles highlighted in blue are new full report additions, and were not part of our daily highlights coverage during the conference. We are already looking forward to next year’s Obesity Week in the nation’s capital!

 

Table of Contents 

Detailed Discussion and Commentary

Medical Obesity Therapies

Early Weight Loss with Liraglutide 3.0 mg Predicts 1-Year Weight Loss and is Associated with Improvements in Clinical Markers

Ken Fujioka, MD (Scripps Clinic, La Jolla, CA)

Dr. Ken Fujioka (Scripps Clinic, La Jolla, CA) presented a new analysis of pooled data from the SCALE Obesity and Prediabetes/SCALE Diabetes trials of Novo Nordisk’s obesity drug Saxenda (liraglutide 3.0 mg) in order to identify an early response criterion for predicting weight loss. Analysis of the data indicated that ≥4% weight loss at 16 weeks is a strong predictor of clinically relevant weight loss at 56 weeks. The investigators defined clinically relevant weight loss as a body weight reduction of ≥5% weight loss and compared efficacy outcomes in early responders to early non-responders to the therapy. The strongest predictor was determined by assessing a composite of the positive predictive value of early responders and negative predictive value of early non-responders. The criterion of ≥4% weight loss at 16 weeks yielded an overall correctly predicted value of 80%, the highest among all other criteria (≥3%, ≥4%, ≥5% weight loss at 8, 12, 16 weeks). Early responders and early non-responders exhibited remarkable disparities in weight loss, with an average of 11% (11.2 kg [25 lbs]) reduction in the former group versus an average of 3% (3.2 kg [7 lbs]) reduction in the latter group after 56 weeks. We hope that these findings can guide clinical decision-making by helping providers discern earlier in the course of treatment whether Saxenda is effective for the patient. Given its injectable administration and the extremely high cost of Saxenda ($1,068/month) and its poor reimbursement and access (we assume most patients are self-pay), an earlier determination of its effectiveness could save patients money, time, and hassle. We hope results from studies like these can be disseminated through treatment guidelines to help healthcare providers learn to most effectively utilize this agent – our sense is that many healthcare providers are unsure of when and how to use obesity drugs in many cases and we believe that greater patient and provider education can help boost the obesity pharmacotherapy field.

Innovative Emerging Pharmacotherapy and Devices Forum

Kevin Grove, PhD (Novo Nordisk Bagsværd, Denmark); Professor Lora Heisler (University of Aberdeen, Scotland); Lee Kaplan, MD, PhD (Massachusetts General Hospital and Harvard Medical School, Boston, MA); David Maggs, MD (Fractyl Laboratories, Lexington, MA); Mark Tager, MD (Ambra Bioscience, San Diego, CA)

This forum, a perennial favorite at Obesity Week, provided a fascinating overview of novel obesity therapies currently under development. We noticed a dichotomy between novel drug therapies targeting the brain versus non-pharmaceutical therapies targeting the gut. In an overarching comment on the state of obesity treatment, Novo Nordisk’s Dr. Kevin Grove (who we had the pleasure of interviewing during Obesity Week 2014) underscored that combination therapy offers the most potential for success. He joked that when it comes to obesity therapy he believes that “1+1=3.” That is, the synergy that arises from targeting multiple mechanisms with two or more drugs may provide benefits beyond what would be expected on a purely additive basis.

  • On the pharmacotherapy front, commentary focused on drugs impinging on the hypothalamic melanocortin pathway. Dr. Lee Kaplan (Massachusetts General Hospital and Harvard Medical School, Boston, MA) highlighted Rhythm Pharmaceuticals’ phase 2 melanocortin 4 receptor (MC4R) agonist setmelanotide. This phase 2 candidate was recently featured in the New England Journal of Medicine for producing sustained and steady weight loss (~4 lbs/week) and marked hunger reduction in two patients with genetic obesity due to rare defects in the pro-opiomelanocortin (POMC) gene. Dr. Kaplan explained that several other genetic obesity conditions are characterized pathophysiology downstream of the melanocortin 4 receptor that setmelanotide targets, suggesting that this drug may have even broader applicability. Dr. Kaplan further pointed out that we do not fully understand the spectrum of the presentation of genetic obesities or how many people have a form of obesity that is setmelanotide-responsive. Dr. Lora Heisler (University of Aberdeen, Scotland) described the promise of 5-HT2C receptor agonists, which reduce appetite via action on POMC-expressing neurons. Her research suggests that 5-HT2C receptor agonists, such as Eisai’s Belviq (lorcaserin), also have a direct effect on glucose homeostasis, independently of alterations in food intake or body weight; this raises the possibility that this drug class may be suitable for the treatment of not only obesity but also the comorbidity of type 2 diabetes.
  • We also heard discussion around novel therapies that impinge on the gut – attempting to mimic the effects of bariatric surgery in a less invasive (and less expensive) way. Noting the effectiveness of bariatric surgery, but expressing doubt over its scalability, Dr. David Maggs of Fractyl Laboratories (Lexington, MA) provided an overview of duodenal mucosa resurfacing (DMR), an endoscopic procedure designed to “rejuvenate” the musical surface of the duodenum by hydrothermal ablation, replicating the duodenal exclusion that occurs in roux-en-Y gastric bypass surgery. Fractyl recently completed the first in-human study of DMR, reporting A1c reductions of 2.5% three months post-procedure for patients who underwent DMR for the long duodenal segment (n=28) and 1.2% for patients who underwent DMR for the short duodenal segment (n=11). Finally, Dr. Mark Tager of Ambra Bioscience (San Diego, CA) discussed the company’s pipeline of novel gut sensory modulating dietary supplements. Composed of a proprietary combination of GRAS-designated (generally regarded as safe) dietary ingredients, these supplements deliver non-nutritive tastants directly to the L-cells in the lower GI-tract, mimicking the effect of food and triggering the release of hormones such as GLP-1, PYY, and oxyntomodulin. This “L-cell triumberate” of hormones, Dr. Tager explained, is a compelling hypothesized mechanism underlying the metabolic effects of bariatric surgery. Ambra plans to begin clinical trials in 2017 to assess the potential of its supplements to deliver long-term weight loss and metabolic improvement.

Engaging Pharmacotherapy and Behavioral Interventions to Minimize Post-Surgical Weight Regain

Louis Aronne, MD (Weil Cornell Medical College, New York, NY)

Dr. Louis Aronne (Weil Cornell Medical College, New York, NY) examined the impact of obesity pharmacotherapies on body weight in individuals who have experienced either inadequate weight loss or weight regain following bariatric surgery. This session was absolutely p-a-c-k-e-d – there was not a single seat available in the room and attendees lined the walls or even sat on the floor. This level of attendance was clearly indicative of the great concern for suboptimal bariatric surgery outcomes as well as great interest in potential solutions – it is of course a huge disappointment and tragedy for patients and providers when very invasive and expensive bariatric surgery isn’t able to achieve the desired weight loss and metabolic outcomes. Dr. Aronne is well-known for promoting a treatment paradigm that incorporates pharmacotherapy after bariatric surgery, shared some remarkable results from a study that utilized this paradigm. The retrospective, two-center study identified patients who had undergone Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) from 2000-2014. An additional criterion was that the patients had been assigned to postoperative pharmacotherapy due to inadequate weight loss or weight regain. Of 319 qualifying patients (RYGB n=258, SG n=61), 54% of them lost ≥5% of total body weight, and 30% of patients, classified as high responders, lost ≥10% of total body weight. Of the medications given, topiramate was the only one that demonstrated a significant weight loss response when administered to postoperative patients, as it doubled their likelihood of losing ≥10% of body weight (p<0.05). Given these results, Dr. Aronne concluded that the optimal time to implement postoperative pharmacotherapy would be when the patient’s weight loss plateaus. However, he stressed the need for more comprehensive, prospective studies. We’re intrigued by Dr. Aronne’s proposed combination approach to weight loss, which further underscores the multifactorial causes of obesity. We hope Dr. Aronne’s work can help encourage greater use of pharmacotherapies can enhance and maintain the weight loss following bariatric surgery.

Policy

Evaluation of the Berkeley Sugar Sweetened Beverage Tax: Did It Affect Prices, Sales Revenue, or Consumption?

Shu Wen Ng, PhD (University of North Carolina, Chapel Hill, NC)

Dr. Shu Wen Ng (University of North Carolina, Chapel Hill, NC) presented an evaluation of the Berkeley sugar-sweetened beverage (SSB) tax, finding that taxed beverages experienced an increase in cost and a decrease in sales. The study analyzed UPC and transaction data from nine locations of two grocery chains inside and outside Berkeley in the first six months since the tax’s implementation in March 2015. Regardless of location, taxed beverages were priced higher than non-taxed beverages by an average of  $0.70 per ounce. Sales of taxed SSB fell by 8.5% (p<0.001) in Berkeley and rose by 6.6% in non-Berkeley areas. Interestingly, these non-Berkeley sales increases were more prevalent in stores closer to Berkeley relative to more distant ones, raising the possibility that people travelled outside Berkeley to seek cheaper soda in neighboring towns (although it is impossible to determine this based on the present analysis). Non-taxed beverage sales rose in Berkeley, leaving no change in overall Berkeley beverage sales post-tax relative to pre-tax. Overall, the results demonstrate an average pass-through (revenue growth due to increased costs) of approximately 70% on SSB; there was no significant change in pass-through for untaxed beverages.

  • Although these data suggest a promisingly reduction in the purchase and consumption of SSB in the Berkeley area, the study does have limitations. This study tracked only two out of the six major grocery chains in Berkeley, so the conclusions are not necessarily generalizable to all stores or store types. In addition, Dr. Ng noted that this study was unable to account for other cofounding factors that may have occurred in the pre-tax and post-tax periods, nor whether the changes in pre- and post-tax sales revenue were due to changes consumer or distributor behavior, such as people purchasing SSBs from other stores. A one-year evaluation is currently under review. Nonetheless, the study supports many thought leaders’ avocation of the soda tax. Indeed, during the recent National Academy of Medicine meeting on the 30-year rise in obesity and type 2 diabetes Drs. Steven Gortmaker and Kelly Brownell discussed the enormous healthcare costs that could be saved and tax revenue that could be collected if soda taxes were implemented more widely. Philadelphia and Berkeley have already passed soda taxes, and San Francisco, Oakland, Albany, CA, and Boulder as well as Chicago are in the midst of debates – we believe the momentum is on and that we’ll look back upon this time and see it as a period of tremendous success.

The Truth We Don’t Want to Hear: Have Policies Increased Obesity Disparities?

Daniel Taber, MD (University of Texas, Austin, TX)

In this provocative talk, Dr. Daniel Taber (University of Texas, Austin, TX) makes the case that well-intentioned policy measures to reduce the prevalence of obesity “work far less often than we’d like to admit,” and increase the socioeconomic disparity in obesity incidence. Los Angeles’ ban on the construction of new fast food restaurants is an example of this phenomenon: although the policy seems quite promising on paper, it had almost no impact, except for a minor benefit in low-risk affluent populations (thereby widening the community’s already vast obesity disparity). Dr. Taber believes that flaws in the process of translating research to policy are to blame for these disparities. “If obesity is complex and politics is complex,” he asked rhetorically, “why do we apply research to policy in a non-complex way?” He offered two hopeful suggestions for how to improve our approach to obesity: comprehensive, multidisciplinary policy change (such as Philadelphia’s simultaneous implementation of soda taxes, school food policies, and activity recommendations) or shifting to policy targets upstream of obesity, such as minimum wage, housing, or transportation systems. The latter suggestion is a crucial one: Dr. Taber suspects that the major shortcoming of current obesity policies is that they do not adequately address the structural determinants of obesity. He envisions a future in obesity policy development where instead of focusing on single factors such as fast food or soda (what he terms the “trees”), policy makers focus on patterns of behavior, systemic structure, and individual mindsets underlying the obesity epidemic (the “forest”).

Healthcare Policy and Treatment Barriers

Bartolome Burguera, MD, PhD (Cleveland Clinic, Cleveland, OH); Ted Kyle (ConscienHealth, Pittsburgh, PA)

A great deal of discussion focused on healthcare policy and structural barriers to obesity treatment, namely under-diagnosis and perceived lack of insurance coverage for obesity treatment. A poster by Dr. Bartolome Burguera (Cleveland Clinic, Cleveland, OH) and colleagues underscored the prevalence of obesity under-diagnosis. A review of nearly 325,000 electronic health records from the Cleveland Clinic revealed that only 48% of individuals with obesity (BMI > 30 kg/m2) and 75% of individuals with severe obesity (BMI > 40 kg/m2) had received a formal diagnosis in the form of ICD-9 documentation. Without a formal diagnosis it is difficult to imagine a pathway toward the treatment and multidisciplinary support required for successful weight loss. Furthermore, during an absolutely packed symposium on the subject of policy and obesity treatment access, Dr. Ted Kyle (ConscienHealth, Pittsburgh, PA) presented the results of an online survey measuring consumer perceptions of health insurance coverage for obesity treatment (n=17,565). The majority of respondents (60-70%) indicated that their health insurance would cover the costs of hospital stays, doctor’s appointments, and blood pressure medications, but ≤20% felt confident that their insurance would cover obesity treatment measures such as medical weight management programs, drugs, and bariatric surgery. Regardless of the actual coverage statistics among US insurance plans, this work importantly reveals that consumers do not perceive obesity care as being covered – another potential factor discouraging them from seeking care.

The Inside Scoop on Federal School Nutrition Policy Changes: A Report from the USDA

Donna Martin (Burke County School Nutrition Program, Waynesboro, GA)

Director of the Burke County School Nutrition Program Ms. Donna Martin (Waynesboro, GA) provided an inspiring presentation on the initiatives she implemented to improve nutrition in public schools in her county. Going above and beyond the guidelines for healthy school lunches stipulated in the Healthy Hunger Free Kids Act of 2010, Ms. Martin spent a great deal of effort in establishing initiatives such as serving 65 types of fruits and vegetables each week, redesigning cafeterias to be brighter and more attractive places to eat lunch, and offering spice stations for students to substitute sodium in food. As director of the largest rural county in the state, we were so pleased when Mr. Martin remarked that the children in her county are eating more fruits and vegetables than their parents (!) and that the healthy food now available in Waynesboro schools is sourced from local farms. Of course, carrying out and sustaining these initiatives has had its challenges – most notably the labor costs required to train employees to make so many diverse meals from scratch. Changing the perception of young children to enjoy eating whole grains, fruits, and vegetables is another challenge, but Ms. Martin noted that even simple acts such as cutting up fruit beforehand creates more appeal for students. “There’s plenty to eat,” Ms. Martin remarked, “but the problem is that kids are eating pizza and French fries all the time so they’re not used to that.” For the sustainability of these programs and their successful implementation across the country, Ms. Martin called for more research on school nutrition, especially since the perception of school nutrition has been largely negative and unhealthy. We are inspired by this example of policy change to combat the obesogenic environment that unfortunately pervades a majority of US school cafeterias.

Effect of Financial Incentives and Restrictions on Food Purchases in a Food Benefit Program

Simone French, PhD (University of Minnesota, Minneapolis, MN)

Dr. Simone French (University of Minnesota, Minneapolis, MN) presented results from a 3- month grocery assistance program study of 279 low-income adults not in the SNAP program. Subjects were randomized into three groups: (i) a control group that followed the SNAP program restrictions; (ii) an incentive group that rewarded a 30-cent bonus per dollar spent on fruits and vegetables; and (iii) a restricted group that did not allow for the purchase of sugar-sweetened beverages (SSB), sweet baked groups, and candies. Purchases were monitored via pre-paid cards and receipts. The resusts of this study demonstrated that there were no statistically significant differences in overall purchasing behavior between the conditions (p<0.56), but the incentive group did show a slightly greater increase in fruit (but not vegetable) purchases while the restricted group showed a significant reduction in purchases of SSB (p<0.0001) and sweet baked goods (p<0.01). This study provides preliminary evidence to evaluate incentives and restrictions in SNAP-enrolled populations, but is limited insofar as participants could have purchased SSB and other unhealthy goods with their own funds, thus skewing the  results.

Downsizing: Policy Options to Decrease Portion Size

Susan Jebb, PhD (University of Oxford, UK)

Dr. Susan Jebb (University of Oxford, UK) described two studies assessing the impact of portion size in adults with overweight and obesity. One study (n=33) demonstrated that reducing breakfast portions leads to a day-long reduction in energy intake. Participants who ate a smaller breakfast displayed reduced post-prandial GLP-1 and GIP levels, but displayed no significant difference in ab libitum energy intake during lunch. A second study involved intake of French fries in a canteen setting, demonstrating that a 50% decrease in portion size led to a 35% decrease in intake. These studies support the notion that smaller portions reduce food intake, and suggest that portion size could thereby be a potential target of policy action. Dr. Jebb noted that there are currently no special guidelines for portion sizes, and consumer awareness of appropriate portion sizes is poor. She suggested better education for consumers, restrictions on promotions for larger-sized packages in grocery stores, and introducing tableware shapes that promote smaller portion sizes. More research is needed to provide evidence of the effectiveness of interventions to decrease portion sizes, though opportunities for intervention may initially be greater in public sector environments or places where food is controlled, such as in schools or workplaces. An important first step, Dr. Jebb noted, is public acceptance of the importance of portion size. This is required to facilitate government action in breaking cycles of not only portion sizes, but the social norms of consumer demand.

Lifestyle Intervention

Innovative Self-Regulation Strategies Reduce Weight Gain and Improve Cardiovascular Risk Factors in Young Adults: The Study of Novel Approaches to Weight Gain Prevention (SNAP)

Rena Wing, PhD (Brown University, Providence, RI)

Dr. Rena Wing (Brown University, Providence, RI) presented two year results from the Study of Novel Approaches to Weight Gain Prevention (SNAP), demonstrating the effectiveness of a lifestyle modification program to prevent weight gain and improve glycemic control in young adults. Noting that weight gain in young adulthood (ages 18-35), versus weight gain in other life stages, occurs at the fastest rate, is associated with worsening in cardiovascular risk factors, and has the greatest negative effects on cancer risk and morality, Dr. Wing argued that preventing weight gain in young adulthood is a public health issue of paramount importance. In the SNAP study, young adults (n=599; BMI: 21-30 kg/m2) were randomized to receive one of two self-regulation interventions: the “large changes” intervention involved an initial recommendation of 5-10 lb weight loss to buffer against future weight gain by temporarily reducing caloric intake by at least 500 calories per day and exercising 250 minutes/week; the “small changes” intervention emphasized making small daily changes to prevent weight gain, reducing dietary intake by 100 calories/day and exercising enough to burn an additional 100 calories/day (approximately 2,000 extra steps). Both interventions emphasized weighing oneself daily to maintain awareness of target weight. The interventions involved 10 face-to-face meetings over the first four months of treatment, followed by biannual online refresher courses for the remainder of the trial. Weight change after two years was a loss of 0.78 and 1.5 kg in the small and large intervention groups, respectively, and a gain of 0.54 kg in the control group (p<0.001). Furthermore, the large change intervention produced significantly greater improvements in fasting insulin and HOMA-IR than the control group (-1.49 and -.28 uU/ml respectively for insulin, p=0.009  and -0.33 and -0.03, respectively for HOMA-IR p=0.005).  Thus, such lifestyle interventions not only prevent weight gain but also produce metabolic benefits. Dr. Wing noted that even though these changes are modest after two years, the effects could multiply over time. To evaluate this, an extended version of the study, SNAP-E, will follow participants through six years of follow up, additionally assessing how their cardiovascular risk factors are influenced by the weight gain prevention program. More on the SNAP study can be found in its original JAMA Internal Medicine publication.

Engaging Minorities in Weight Programs

Nia Mitchell, MD (University of Colorado, Denver, CO); Flavia Mercado, MD (Emory University, Atlanta, GA); Nicolette Teufel-Shone, PhD (University of Arizona, Tucson, AZ)

A symposium on engaging minorities in weight programs reinforced, once again, that there is no one-size-fits-all solution to weight loss in light of the vast racial, ethnic, and cultural diversity in American society. Dr. Nia Mitchell (University of Colorado, Denver, CO) reviewed the results of the recently-completely SWITCH (Senior Wellness Initiative and TOPS [Take Off Pounds Sensibly] Collaboration for Health), a project designed to address obesity in African American women over the age of 50. According to Dr. Mitchell this is the demographic most likely to develop obesity, due to a combination of cultural views about acceptable body weight and unavailability of culturally-sensitive weight loss interventions (for context, 82% of African American women were overweight or obese in 2014). Through a low-cost series of peer-led weekly meetings featuring lessons on nutrition and exercise, the project showed preliminary success: the program had an impressive 79% retention rate after 52 weeks, and after one year 33% lost up to 5% of their initial body weight, and 48% lost over 5% of their initial body weight (n=48). Next, Dr. Flavia Mercado (Emory University, Atlanta, GA) presented strategies to engage the Hispanic community in weight loss programs – a prominent issue because only 5% of physicians are Hispanic, and the rate of obesity in Hispanic populations is twice that of non-Hispanics. Dr. Mercado underscored the importance of reducing early childhood obesity among Hispanics by educating families on obesity in a culturally-sensitive way and knowing how to tailor this messaging for particular communities (“not all Spanish is the same”). Finally, Dr. Nicolette Teufel-Shone (University of Arizona, Tucson, AZ) explored strategies that Native American communities have developed to address weight loss. Dr. Teufel-Shone emphasized that because the Native American community has strong social cohesion, the best strategies to promote healthy choices would be team challenges, engaging leadership and visibility, and changing community norms and tribal policies. Overall, these presentations thoughtfully illustrated that various communities view obesity in nuanced and different ways, so obesity management interventions must be tailored thoughtfully for each unique group.

Intervention Implementation in Schools and Student Outcomes in the Massachusetts Childhood Obesity Research Demonstration (MA-CORD) Project

Kirsten Davison (Harvard University, Boston, MA)

Ms. Kirsten Davison (Harvard University, Boston, MA) presented results from the two-year CDC-funded MA-CORD (Massachusetts Childhood Obesity Research Demonstration) project, aimed at decreasing the incidence of childhood (ages 2-12) overweight and obesity. Working with the Massachusetts Department of Public Health in low-income communities, Ms. Davison implemented two types of school interventions: Eat Well & Keep Moving for fourth and fifth grade students, and Planet Health for sixth and seventh grade students. Both of these school interventions were evidence-based curricula incorporating teacher training and education on nutrition and physical activity. Ms. Davison evaluated the effectiveness of these programs in two communities, tracking the percentages of students with obesity and measuring changes in the percentage of students meeting healthy behaviors (based on student self-reports of their diet, physical activity, and media usage). After 2 years of this intervention, obesity rates significantly decreased among seventh-grade students (p<0.049). This was not the case for any other grade, perhaps because the seventh-graders received the greatest amount of intervention efforts compared to the others. Additionally, among all students overall, there was a significant increase in water consumption (p<0.0001 for one community, p<0.05 for the other). There was no significant pre-post differences identified for juice consumption, fruit and vegetable consumption, sleep, and physical activity. Teachers who were surveyed after the program responded positively and continued to implement the program, though materials will continue to be revised and redeveloped to ensure sustainability and further successes. Promoting a culture of health in schools is clearly a gradual process, and we look forward to learning the longer-term results of the CORD project.

Additional Topics

The Gut Microbiome: An Environmental Factor in Developing Obesity and Metabolic Syndrome?

Ronald Kahn, MD (Joslin Diabetes Center, Boston, MA)

The esteemed Dr. Ronald Kahn (Joslin Diabetes Center, Boston, MA) delivered a keynote lecture emphasizing the complex interplay between genes, environment, and the gut microbiome in the development of obesity. Dr. Kahn drew upon his own research, recounting how his lab has observed a differential response to a high-fat diet between two genetically distinct mouse lines – where B6 mice are obesity prone, 129 mice appear show obesity resistance. Responses to diet can also dependent on external environment. Dr. Khan explained how 129 mice ordered from different breeding facilities (signaling different diets and animal care techniques) display significantly different gut microbiome profiles which, despite their identical genetic background, leave one 129 strain with even greater obesity-resistance than the other. As further demonstration of the microbiome’s plasticity, Dr. Kahn’s team determined that after three generations of living in the same environment, mice of different genetic and environmental backgrounds (the B6 mouse line and the 129 mouse lines from different facilities, all of which had previously demonstrated very different phenotypes) now exhibited a remarkably similar, though not identical, microbiome profile and weight gain response to a high-fat diet. Altogether, this body of work underscores the incredibly complex relationship between genes, the environment, and the microbiome to determine an organism’s metabolic phenotype. Microbiome research remains in its infancy, but the topic is certainly exploding with interest – the session moderator remarked that Obesity Week 2015 featured only a single microbiome talk, whereas the current meeting features entire symposia dedicated to the subject. While several unanswered questions remain, the microbiome’s influence on metabolism is becoming more clear. The exciting implication of this is that the microbiome could be the next target for advanced obesity therapies.

  • Dr. Kahn’s research has identified certain single bacterial genuses driving metabolic phenotypes. For instance, Clostridiales bacteria are correlated with body weight, Clostridium bacteria are correlated with liver weight and adipose inflammation, and Lactobacillus gasseri bacteria are correlated with blood glucose. This finding drove most of the Q&A session, during which Dr. Kahn commented that the next task for scientists is to identify the most important single bacterial species within these genuses driving the effects on weight, adiposity, and blood glucose. From there, it may be possible to design probiotics containing a combination of desired species of bacteria to improve specific metabolic outcomes. We’re so intrigued by this prospect for a novel obesity and diabetes therapy, though again, we must acknowledge that microbiome research remains early-stage with much room for growth in the years to come.

Microbial Changes in Relation to Obesity, Sugar Intake, and Health Status in Humans and Animal Models

Anthony Fodor, PhD (UNC Charlotte, NC)

With incredible enthusiasm, Dr. Anthony Fodor (UNC Charlotte, NC) shared highlights of microbiome research in obesity over the past 10 years, underscoring great progress, despite the lingering questions that remain. He made special note of the ease of study replicability and the decrease in DNA sequencing costs, both of which have facilitated progress in the field. That transfer of obesity between mice via transplant of the microbiome has been successfully replicated, Dr. Fodor explained, and has established consensus over the role the microbiome plays in obesity development. Similarly, researchers have come to agree that a juvenile diet can impact the later-life microbiome. That said, the impact that different drugs have on the microbiome remains to be fully understood. Dr. Fodor suggested that the microbiome should be carefully tracked when patients are taking different pharmacotherapies in order to elucidate the confounding effects of drugs. We were inspired by Dr. Fodor’s passion for the microbiome (and by his good humor throughout the presentation!). The microbiome is increasingly talked about in diabetes and obesity circles, and we hope to see future progress on the microbiome as a target for therapies, though we understand that much more research and investment may be necessary as a means to this end.

Opening Session and Keynote: Neural and Physiological Mechanisms Involved in Human Energy Balance

Sadaf Farooqi, PhD (University of Cambridge, UK)

Speaking to an absolutely packed hall, Dr. Sadaf Farooqi kicked off Obesity Week 2016 by addressing how the prevalence of stigma against obesity in the general population is at odds with the breadth of evidence suggesting that many genetic variants predispose certain individuals to obesity. Dr. Farooqi asserted that a deeper understanding of genetic determinants would ameliorate the widespread stigma against obesity. Her presentation surveyed the literature to describe the genetic determinants of energy homeostasis, with a particular focus on studies evaluating loss of function mutations in the leptin, MC4R, and KSR2 genes. On the other hand, she also explored a rather counterintuitive and intriguing alternative approach to studying obesity – investigating the physiology of thinness to inform drug discovery for obesity. Dr. Farooqi concluded by calling for an integrated, multidisciplinary approach to treating obesity, citing the extensive network of pathways that act to protect against starvation and thus increase propensity for accumulation of adipose tissue. The audience was very receptive to her lively talk, peppered with plenty of humor and anecdotes. We greatly appreciated Dr. Farooqi’s comprehensive overview of the cutting edge of obesity research and we can only hope that some of this early-stage discovery work can be translated into viable therapies. The obesity field has been increasingly challenging – with Novo Nordisk most recently acknowledging that the field is increasingly becoming a single-player market – and we hope that this does not discourage innovative biotech firms or established pharmaceutical companies from investing in this field.

The Early Home Environment Modifies Genetic Influence on Child Weight

Clare Llewellyn, PhD (University College London, UK)

Dr. Clare Llewellyn (University College London, UK) presented results to support that the early home environment modifies the heritability of BMI, such that the genetic influence on weight is stronger in more obesogenic home environments. Using subjects from the UK’s Gemini twin cohort, Dr. Llewellyn and colleagues collected anthropometric data for 1,850 twin pairs born in 2007, as well as information about the home environment (in terms of the availability of and parental policies surrounding food, physical activity, and media) for these twin pairs at age 4. Twins share upwards of 50% of their genes (depending on whether they are identical or fraternal) but 100% of their home environment; therefore, the extent to which BMI matches in twin pairs reflects how genetically-driven (rather than environmentally-driven) weight is. Using maximum likelihood statistical techniques, Dr. Llewellyn quantified the correlation between genetic influence and weight as 0.86 (95% CI: 0.68-0.89) in “high risk” (i.e. more obesogenic) homes, versus only 0.39 (95% CI: 0.21-0.57) in “low risk” homes. On a more granular level, the correlation between genetics and weight was 0.83 (95% CI: 0.65-0.87) in homes with unhealthy food options (versus 0.40 [95% CI: 0.23-0.59] in homes where physical activity was encouraged) and 0.80 (95% CI: 0.60-0.84) in homes where physical activity was not encouraged (versus 0.49 [95% CI: 0.33-0.65] in homes where physical activity was encouraged). Although replication is necessary to validate these findings, these results importantly suggest that, even for people with a high genetic predisposition for weight gain, modification of the home environment could limit the extent to which this predisposition is expressed. The finding that the influence of genetics depends on environmental context may also perhaps explain the current lack of consensus in the literature on the heritability of BMI: 32 existing studies report that BMI is between 31-90% heritable, with a mean of 73%).

Macronutrients, Calories, or Physical Activity? Game of Truths

David Ludwig, MD PhD (Boston Children’s Hospital, Boston, MA); Kevin Hall, PhD (NIH, Bethesda, MD)

A symposium on the effects of diet and exercise on weight loss evolved into an indirect debate between Dr. David Ludwig and Dr. Kevin Hall on the importance of macronutrient content versus simple caloric content for weight loss. Dr. Ludwig (Boston Children’s Hospital, Boston, MA) is well known as a champion of the carbohydrate-insulin model, which points to high-carb, low-fat diets as the culprit for the nationwide rise in obesity. He emphasized that major evidence for this point of view comes from five recent meta-analyses, all of which demonstrate inferiority of low fat diets compared to higher fat diets for weight loss. (Specifically, a 2015 meta-analysis in Lancet, demonstrating that low-carbohydrate diets led to significantly greater weight loss [weighted mean difference of 1.15 kg] than low-fat diets in a review of 18 recent weight loss trials.) Dr. Ludwig also reviewed animal and human studies showing less fat accumulation and faster metabolic rate on higher fat and low glycemic index diets. Dr. Hall (NIH, Bethesda, MD), by contrast, hypothesizes that fat loss is a balance of fat intake and net fat utilization. He believes that although reduced carbohydrate intake shifts the body into a fat oxidation mode, it does not equate to fat loss. He qualified his retort by stating that many of his points actually coincided with the carbohydrate-insulin model, save for a few key details. However, Dr. Hall did have room for a caveat – although he disagreed with the assumptions of the carbohydrate-insulin model, he conceded that there may be positive health effects of reduced carbohydrate intake that do not relate to energy expenditure.

  • To conclude the symposium, Dr. Barry Braun (Colorado State University, Fort Collins, CO), not a participant in the contentious diet debate waged by the previous speakers, added physical activity to the discourse. Surveying an extensive literature, he emphasized that physical activity had a dosage effect such that improved outcomes in baseline blood pressure and blood glucose in increments correspond to the weekly duration of an individual’s activity. Though this is perhaps intuitive, it emphasizes the importance of regular and frequent exercise as an adjunct to a healthy diet.

Reducing Weight Bias in Health Care

Nanette Adams (Harahan, LA); Trina Histon, PhD (Kaiser Permanente, Oakland, CA); Kimberly Gudzune, MD (Johns Hopkins University, Baltimore, MD)

A packed symposium on reducing weight bias in healthcare featured valuable patient, clinical, and systemic perspectives on how to reduce the scourge of obesity stigma. Obesity counselor Ms. Nanette Adams (Harahan, LA) shared the physical, emotional, and social hardships she endured being obese from a young age, and told the remarkable story of her years undergoing lap band, sleeve gastrectomy, and roux-en-y gastric bypass surgery (all three major bariatric surgery procedures!). As both a patient and a provider, Ms. Adams poignantly described her struggles with obesity care and how healthcare providers can work to better mitigate this. She urged that healthcare providers should use “people first” language and challenged the HCPs in the audience to evaluate their own subliminal biases toward patients with obesity. “Believe your patients when they say what they are doing. Don’t dehumanize them,” she advised, “understand that your words do impact them – they may leave and cry for hours because you used the wrong words.” Ms. Adams reflected that by decreasing her own bias, she was able to better intellectually understand health and weight, in addition to enhancing her empathy for people affected by obesity. She ended her presentation with the inspiring message that “as a patient, I am more than my weight.” Next, Dr. Trina Histon (Kaiser Permanente, Oakland, CA) shared some of Kaiser Permanente’s initiatives to address weight bias. Dr. Histon pointed out that seemingly small adjustments – such as ensuring that the facility’s chairs, beds, gowns, and scales can accommodate patients with obesity – can make a huge impact on the patient experience. However, she also noted that, despite these institutional improvements, “we’re not perfect – before you’re a doctor or a nurse you’re still a human being.” Indicating that there is still much to be done in clinical management to reduce weight bias, she also remarked, “we don’t have it all figured out, but we have made a lot of progress.” This was a great talk that we hope receives significant attention.

  • Dr. Kimberly Gudzune (Johns Hopkins University, Baltimore, MD) reviewed the evidence on interventions designed to mitigate weight bias in clinical practice. Dr. Gudzune pointed out that a patient’s obesity immediately shapes a clinician’s attitude, interpretation of symptoms, decision-making, and ultimately treatment, making individuals with obesity vulnerable to receiving less efficacious treatment recommendations. (This bias appears to arise even before physicians begin clinical practice; Dr. Gudzune shared saddening statistics that 74% of US medical students have anti-fat bias and 67% have explicit weight bias.) She urged for more designs and program tests to minimize effects of weight bias in healthcare settings. Interventions including virtual and in-person patient encounters and bariatric sensitivity training have been able to promote stigma reduction and induce empathy in medical students, though other interventions including a four-week curriculum on the controllable reasons of obesity actually increased weight bias among students. Dr. Gudzune noted that these interventions were brief in duration, and more studies are required to conclusively determine best practices. Nevertheless, this is a cogent reminder of the wide scope of weight bias and the need for careful bias reduction.

Clearing Up the Diabetes and Obesity Conundrum

Peter Vash, PhD (UCLA Medical Center, Los Angeles, CA); Charlotte Hayes (Director of Research and Education, Team Novo Nordisk)

This symposium provided clear guidelines for clinicians to follow when treating the growing number of patients with comorbid diabetes and obesity. Dr. Peter Vash (UCLA Medical Center, Los Angeles, CA) explained that the main objective in treating patients with diabetes should be individual glycemic goals within realistic limits. He advocated for the use of SGLT-2 inhibitors and GLP-1 agonists as a way to intensify therapy in obese patients with diabetes, due their weight loss side effects. He further warned clinicians to be aware of any additional medications the patient may be taking with adverse weight gain side effects (anti-depressants are particularly notorious), recommending that these be replaced with weight-neutral alternatives whenever possible. Acknowledging the challenge of treating diabetes and obesity, Dr. Vash noted that the use of medication is part science and part art, and the doctor-patient relationship is “the active ingredient” in the design of an effective obesity and diabetes treatment regimen.

  • ADA Professional Practice Committee member Ms. Charlotte Hayes provided an outline of the most up-to-date ADA Standards of Medical Care, highlighting the newest section added about obesity management for treatment of type 2 diabetes. This section explains that clinicians should design diet, physical activity, and behavioral therapy to achieve an initial 5% weight loss, after which comprehensive weight maintenance should be prescribed. Perhaps the boldest update to these guidelines is an explicit recommendation against the consumption of sugar-sweetened beverages as a means of controlling weight and minimizing cardiovascular risk. On the subject of healthy eating and weight control, Ms. Hayes disclosed that there was no “ideal” eating pattern (i.e., Mediterranean diet, vegetarian, low carb, etc.) that is demonstrated to benefit all individuals with diabetes. Although total energy intake is an important consideration, individuals with diabetes should focus on choosing nutrient-rich whole foods rather than adhering to a “rigid prescription” for diet. Indeed, Dr. Donna Ryan (Pennington Biomedical Institute, Baton Rouge, LA) did mention during the recent Cleveland Clinic Obesity Summit that the best diet is simply the one that people can best stick to.

Weight Loss Maintenance

Holly Wyatt, PhD (University of Colorado, Aurora, CO)

Dr. Holly Wyatt (University of Colorado, Aurora, CO) emphasized one of the biggest challenges for patients living with obesity and their clinicians – maintenance of weight loss. Conference hall attendance is usually indicative of what the “hot button” issues are in conference, and this session was no exception. As with other popular sessions, this one began with a full conference hall, with every seat occupied, attendees lining the walls, and some even sitting on the floor in the aisles. One challenge surrounding the issue of weight loss maintenance, according to Dr. Wyatt, is the lack of a clear definition of precisely what weight loss maintenance is, leading to ambiguous conclusions about long-term trends. In discussing the major contributing factors for weight loss versus weight loss maintenance, Dr. Wyatt noted that at first, caloric intake is the largest contributing factor to acute weight loss. However, physical activity was implicated as the largest contributing factor for maintenance. Regarding effective strategies for weight loss maintenance, she recommended obesity pharmacotherapies. By targeting the phenomenon of metabolic adaptation, these drugs excel at promoting weight loss maintenance (much more so they than do at promoting initial weight loss).

  • The most memorable line from Dr. Wyatt's presentation was a critique of what she perceived as complacency in setting weight loss goals. She explained that "losing as much weight as you can in a finite period of time and THEN maintaining it works better. We are setting the bar too low." This assertion came from her unique perspective of serving as the medical expert in the reality television show "Extreme Weight Loss," where transformative weight loss yielded the best long-term results.
  • Also of note, Dr. Wyatt's reviewed a recent publication in the February issue of Obesity which highlighted the effects of water and non-nutritive sweetened (NNS) beverages in the context of weight loss maintenance. Over the course of this one year study, participants assigned to consume 24 ounces per day of beverages sweetened by non-nutritive sweeteners (versus caloric sweeteners) maintained 6.21 kg weight loss versus 2.45 kg in the group assigned to consume 24 ounces of water daily (n=303, p<0.001). Both study groups consisted of obese (BMI=~33-34), mostly female (~80%) individuals. These results suggest that NNS beverages can be an effective tool for weight loss maintenance – perhaps providing a more palatable alternative for individuals who find it difficult to reduce their consumption of sugar-sweetened beverages.

Pre-Conference Course: Review Course for the ABOM Exam

Maria Collazo-Clavell, MD (Mayo Clinic, Rochester, MN);

The power of adherence was a major theme during a pre-conference review course for the American Board of Obesity Medicine examination, with speakers almost unanimously emphasizing its significance in the context of diets, medication management, exercise, and supplementation following bariatric surgery. Dr. Maria Collazo-Clavell (Mayo Clinic, Rochester, MN) showed data supporting this observation, demonstrating that weight loss is more strongly correlated to diet adherence rather than diet type. She overviewed a classic study by Dansinger et al. in JAMA comparing absolute weight change over 12 months in patients assigned to Atkins, Zone, Weight Watchers, and Ornish diets; no significant differences were observed, and high variability was present in each diet group.  Although these data were published in 2005, the emphasis on adherence is as timely a topic as ever across all categories of obesity care – from nutrition to pharmacotherapy to physical activity. This is a message we heard recently from Dr. Donna Ryan at the Cleveland Clinic Obesity Summit: the best weight loss regimen is, quite simply, the one patients can best stick to.

  • Dr. Collazo-Clavell emphasized that the issue of adherence goes beyond individual willpower: she astutely pointed out that much of the decisions involving food over the past several decades have been made by people other than consumers. According to Dr. Collazo-Clavell, everyday decisions involving food – such as fast food portion sizes and serving sizes of bottled drinks – have all increased dramatically without the input of consumers. This change, she posited, has added to the difficulty of maintaining consistency in diets. In addition, current literature has not progressed in terms of offering an “optimal” supplement regimen. These and other factors act as major barriers to nutritional adherence.
  • The ABOM review session also reviewed previously-reported data supporting the use of diabetes medications co-opted for obesity treatment – most notably canagliflozin, liraglutide, and metformin. These trials demonstrate a trend towards multifaceted treatment of obesity that targets multiple pathways, in order to yield a synergistic effect in weight reduction.

Corporate Symposia

Barriers to Effective Obesity Care: Results from the National ACTION Study (Sponsored by Novo Nordisk)

Lee Kaplan, MD (Massachusetts General Hospital/Harvard Medical School, Boston, MA)

Dr. Lee Kaplan (Massachusetts General Hospital/Harvard Medical School, Boston, MA) presented the results of the Novo Nordisk-sponsored national ACTION study (Awareness, Care, and Treatment in Obesity MaNagement), the first ever study exploring the factors underlying the barriers to weigh management. The conversation on this groundbreaking study continued at a subsequent Novo Nordisk-sponsored corporate symposium. The ACTION study used a questionnaire to survey the attitudes and perceptions regarding obesity in three groups of participants: people with obesity (n=3,008), healthcare professionals (n=606; 83% primary care providers and 17% weight loss specialists), and employers (n=153). These results were concurrently announced in a Novo Nordisk press release. A previous qualitative version of the ACTION study, based on two-hour focus group sessions as opposed to a quantitative survey, were presented last year at Obesity Week 2015.

  • On the patient side, a majority of surveyed individuals with obesity (65%) perceived obesity as a disease, an encouraging sign that public education campaigns have been effective in spreading this message. Paradoxically, however, a huge 95% consider themselves personally responsible for their weight (82% “completely;” 17% “somewhat”). While an encouraging 73% of people with obesity have at some point discussed their weight with a healthcare professional, 36% reported that they did not end up seeking support from this HCP for weight loss and only 16% attended follow-up appointments to specifically discuss their weight. This perhaps underlies the worrisome finding that only 55% of Americans with obesity have received a formal diagnosis. Accordingly, only 51% of people with obesity self-identified themselves as such (48% opted for the perhaps more neutral term “overweight” and 2% described themselves as “normal weight). On average, these individuals have undergone seven serious attempts at weight loss over a lifetime, with only 11% successfully achieving 10% weight loss lasting one year. Frustration over this is reflected in the statistic that 38% of individuals with obesity believe they cannot achieve weight loss “even if they set their mind to it.”
  • Providers widely agree (80%) that obesity is a serious chronic disease and 72% report feeling a “responsibility to actively contribute” to their patients’ weight loss efforts. Although the majority of physicians (67%) indicated that they were “very comfortable” or “extremely comfortable” initiating conversations with their patients about obesity management, a substantial proportion also reported deprioritizing such conversations. Not unexpectedly, about half of HCPs reported having deemphasized discussions of weight due to “limited time” (52%) and “more important issues” to address (45%). Rather startlingly, however, many did so because of a belief that the patient was “not motivated” (27%) or “not interested (26%) in losing weight. Dr. Kaplan pointed out that this reveals a troubling disconnect between words and actions: “If providers view obesity as a serious disease, why isn’t it being addressed as such in clinical practice?”
  • Employers largely understand obesity as a serious disease (62%) but feel fairly little responsibility for actively supporting individuals’ weight loss efforts (46% none; 37% “somewhat”). During the corporate symposium, Dr. Tom Parry (President and Co-Founder, Integrated Benefits Institute, San Francisco, CA), an esteemed expert on the intersection between health and business, pointed out that the employer’s role in obesity care runs far deeper than simply the provision of health insurance. After all, people spend over 40 hours/week at the workplace; thus, employers have the power to structure their environment to create or alleviate a culture of health. Health conditions impact workplace productivity, not only through costs of medical appointments and prescription drugs (typically the main variables employers focus on) but also through absenteeism and lost productivity. Although obesity is the least costly chronic condition for employers in terms of medical appointments and prescription drugs alone, it becomes the second most expensive (after depression) when absenteeism and lost productivity are also accounted for. Thus employers should view the active promotion of obesity management as a mutually beneficial arrangement that both promotes employee health and makes economic sense. Though many workplaces have wellness programs that 72% of employers and 64% of HCPs find valuable, only 17% of people with obesity agree. This constitutes a resounding call for a restructuring of these programs – and clearly underscores a need for clearer communication between patients and providers on patients’ weight loss intervention progress.
  • Together, Dr. Kaplan dichotomized these results as being indicative of (i) barriers to seeking care; and (ii) barriers to receiving care. People with obesity may feel discouraged from seeking care because of the widespread perceptions that weight loss is exclusively the individual’s responsibility, that long-term weight loss is rarely achieved, and that employer wellness programs have limited value. Likewise, barriers to receiving care may exist because, even when weight is discussed, “obesity” is rarely a diagnosis and follow-up care is uncommon.
    • These learnings from the aptly-named ACTION study parallel nicely with the call to action issued by The Obesity Society (TOS) for more engaged obesity care. Throughout the conference, in the spirit of National Obesity Care Week, attendees have been encouraged to sign the pledge to treat obesity seriously and “Take 5” – that is, dedicate five minutes out of each appointment to have a productive and empathetic conversation with their patients about weight management. Eye-catching signs adorn the conference hall reading the pledge: “I believe obesity isn’t just a problem. It’s a disease that warrants serious evidence-based treatments – nutritional and physical activity guidance, intensive behavioral counseling, drug therapy, and surgery. I agree to learn more and help more. I treat obesity seriously.”

Improving Outcomes in Difficult-to-Treat Patients with Obesity: Challenge Accepted (Sponsored by Novo Nordisk)

Donna Ryan, PhD (Pennington Biomedical Research Institute, Baton Rouge, LA)

At this Novo Nordisk-sponsored corporate symposium – to thundering applause and laughter – powerhouse obesity expert Dr. Donna Ryan (Pennington Biomedical Research Institute, Baton Rouge, LA) issued her “Ten Commandments of Obesity Management.” At the core, her recommendations all center on the notion that good weight management is good chronic disease management; rather than focusing on body weight, BMI, and an ideal target weight, physicians should encourage their patients to frame weight loss in the context of overall body health. Dr. Ryan noted that she has detected an encouraging shift in obesity management guidelines away from BMI-centricity toward a more personalized approach where the patient’s unique health risks, not their body size, drives treatment intensity. Of course, the actual implementation of these improved treatment guidelines is an ongoing challenge: obesity care mostly rests largely with primary care physicians, who do not always receive sufficient education on the latest behavioral, pharmacological, and surgical weight management techniques; furthermore, reimbursement remains difficult for obesity therapy. Dr. Ryan’s Ten Commandments of Obesity Management provide a simple framework to make obesity care more tractable for health care providers. They are as follows:

  • (1) Thou shalt use BMI as part of the electronic health record, but thou shalt not use it as a diagnosis that directs treatment;
  • (2) Thou shalt consider the patients’ genetic/ethnic background as part of the BMI and waist circumference risk assessment;
  • (3) Thou shalt not treat on BMI alone. Thou shalt remember that waist circumference is a risk factor and use it and other health risks to direct treatment;
  • (4) Thou shalt not worship at the shrine of ideal weight, but rather extoll the virtue of good health and set a weight goal based on a health target;
  • (5) Nor shalt thou worship at the shrine of any one diet;
  • (6) It is your job to teach the skills training in behaviors to produce weight loss or to refer the patient to someone who can;
  • (7) Thou shalt not impugn thy patient’s willpower, but rather prescribe aids to help thy patient adhere to the diet and exercise plan;
  • (8) Thou shalt prescribe medications according to the label, and if the patients lose 5% or more, thou shalt continue those medications.
  • (9) Thou shalt refer patients for bariatric surgery, especially if they suffer metabolic complications of obesity;
  • (10) Thou shalt expect a relapse if treatments are stopped.

Top 5 Strategies for Success: An Integrated Approach to Obesity and T2D Patient Management (Sponsored by Cleveland Clinic and Medtronic)

Bartolome Burguera, MD, PhD (Cleveland Clinic, OH)

In this corporate symposium co-sponsored by the Cleveland Clinic and Medtronic, Dr. Bartolome Burguera (Cleveland Clinic, OH) provided a most-welcome “reality-check” – “we treat the comorbidities, but we don’t treat the main problem, which is obesity.” He pointed out three problems with our current approach to obesity care that impede directed treatment: (i) Obesity is not widely recognized as a disease, and without formal diagnosis, it can be difficult to implement an intervention; (ii) Only a fraction of people with obesity are referred to bariatric surgery, which Dr. Burguera called the most effective therapy for obesity; and (iii) Cost barriers, safety concerns, and general patient/provider reluctance to talk about obesity as a real disease lead to under-utilization of the therapeutic tools that are available for obesity management. Dr. Burguera spoke boldly about a bias that exists among HCPs, in that they assume people with obesity are difficult to treat. We appreciated his willingness to bring these issues into the limelight, and we hope that with greater education, awareness, and weight management guidelines HCPs are better supported in providing optimal obesity care – this was the theme of Dr. Donna Ryan’s (Pennington Biomedical Research Center, Baton Rouge, LA) keynote address at AADE 2016, which continues to resonate with us. Overall, Dr. Burguera’s talk was a tremendous wake-up call to confront obesity as a disease and to stop missing opportunities to treat it.

Posters

3-Year Efficacy and Safety for Liraglutide 3.0 mg in Adults with Obesity/Overweight, Prediabetes and Baseline BMI <35 vs ≥35 kg/m² in the SCALE Obesity and Prediabetes, Double-Blind, Placebo-Controlled Trial

A-P Cancino, MD; B McGowan, MD, PhD; X Pi-Sunyer, MD; F Greenway, MD; C Le Roux

The three year results of Novo Nordisk’s phase 3 SCALE trial were presented in poster form, demonstrating the enormous potential of the GLP-1 agonist liraglutide to produce weight loss and health-related quality of life improvements in people with prediabetes. A multinational population of individuals with prediabetes and overweight or obesity were advised to adopt lifestyle changes (500 calories/day reduction and ≥150 min/week exercise) and randomized to receive either once-daily liraglutide 3.0 mg (n=1505) or placebo (n=749). Individuals treated with liraglutide were significantly more likely to achieve categorical weight loss over three years, with 25% losing between 5-10% body weight, 14% losing between 10-15% body weight, and 11% losing ≥15% body weight (versus 14%, 7%, and 3% of individuals on placebo, respectively). This is remarkable to see how well the “super-responders” are doing, three years out. 40% of individuals on placebo gained weight over the course of the trial, as compared to under 15% of those treated with liraglutide. Furthermore, across both the liraglutide and placebo treatment arms, with greater categorical weight loss came significantly larger improvements in health-related quality of life (as measured by the IWQOL-Lite questionnaire, measured on a 100-point scale; p <0.001). From an overall baseline IWQOL score of ~71, individuals who lost up to 5% body weight (n=554), 5-10% body weight (n=358), 10-15% body weight (n=201), and ≥15% body weight (n=132) respectively increased their scores by an average of approximately seven, 10, 13 and 16 points. These results highlight the promise of liraglutide as a treatment for prediabetes – a condition that is present in epidemic proportions (86 million people in the US alone), but for which there are currently no approved therapies. Although the fact that liraglutide is already approved for both diabetes (as Novo Nordisk’s Victoza, a 1.0 mg dose) and obesity (as Novo Nordisk’s Saxenda, a 3.0 mg dose) represents an important advantage in acquiring a prediabetes indication, we continue to strongly believe that far more work is necessary (e.g., getting prediabetes guidance from FDA) before any progress could be made on this front.

  • The SCALE trial is distinctive in its use of quality of life outcomes. To echo the sentiment of the recent FDA workshop on outcomes beyond A1c, we are pleased to see outcomes beyond body weight beginning to emerge in the obesity/prediabetes arena. Clearly effective obesity and prediabetes care involves so much more than pure weight loss, and we should strive for pharmacotherapies that, like liraglutide, improve the lives of individuals on top of their weight benefits. One key would be proving quality of life is connected to adherence – of course we know this is true, but it’s got to be proven.

Proof of Concept for Treatment of a Second Rare Genetic Disorder of the Leptin-Melanocortin Pathway: Successful Therapy of Extreme Obesity in a Leptin-Receptor (LepR) Deficient Patient with the Melanocortin-4 (MC4) Receptor (R) Agonist Setmelanotide

C Poitou-Bernert, MD; S Wiegand, MD; A Gruters, MD; H Connors, MS; K Gottesdiener, MD; L Van der Ploeg, PhD; F Fiedorek, MD; S Farooqi, MD, PhD; H Krude, MD; K Clément, MD, PhD; S Wiegand, MD

Rhythm Pharmaceuticals presented a poster detailing positive initial phase 2 results supporting the safety and efficacy of the novel and potentially first-in-class melanocortin-4 receptor (MC4R) agonist setmelanotide in the treatment of leptin receptor (LepR) deficiency obesity. LepR deficiency obesity is an ultra-rare orphan disease, affecting ~1% of individuals with severe, early-onset obesity (between 500-2,000 Americans, according to Rhythm’s estimates); currently there is no approved treatment for LepR deficiency obesity. The poster detailed data for the first patient enrolled in this open-label clinical trial, who experienced substantial reduction of both weight and hunger. With setmelanotide treatment, the LepR patient lost almost 20% body weight over the course of 22 weeks (56.4 lb weight loss from a baseline of 288 lbs). Furthermore, the patient experienced a substantial reduction in subjective hunger from a baseline of 9 (on a 0-10 Likert scale with 0 representing no hunger and 10 representing extreme number) to 1.5. Setmelanotide was well-tolerated with no severe adverse events reported. These results provide important proof-of-concept for setmelanotide’s potential to treat this orphan disease. Rhythm is currently in the process of enrolling more candidates into the clinical trial in hopes of demonstrating setmelanotide’s effectiveness in more LepR patients. This same trial was recently featured in the New England Journal of Medicine for showing sustained and steady weight loss (~4 lbs/week) and marked hunger reduction with setmelanotide in two patients with a different rare form of genetic obesity, pro-opiomelanocortin (POMC) deficient obesity. As we heard from Dr. Lee Kaplan (Massachusetts General Hospital/Harvard Medical School, Boston, MA) at a symposium on promising novel therapies in obesity care on Day #1 of the conference, several other genetic obesity conditions are characterized pathophysiology downstream of the melanocortin 4 receptor that setmelanotide targets, suggesting that this drug may have even broader applicability beyond LepR and POMC deficient obesity.

  • To complement this clinical trial, Rhythm has also launched the Genetic Obesity Project to support greater genotyping and diagnosis of genetic forms of obesity, such as POMC and LepR deficiency. The spectrum of the presentation of genetic obesities is not well-understood, and it is very plausible that a substantial proportion of people with obesity may have a form of the disease that is setmelanotide-responsive.

Effects of Sugar-Sweetened Beverage Intake on Obesity Treatment Outcomes

R Wing, PhD; T Leahey, PhD; G Farenga

This study demonstrated that cessation of SSB intake led to significantly improved weight loss outcomes in individuals (n=214) enrolled in a three-month internet behavioral weight loss program. Individuals who drank SSBs at baseline but stopped once beginning the online weight loss program lost 6.3% body weight compared to only 4.1% in participants who did not change their SSB intake and 3.1% in participants who increased their SSB intake during the program (p<0.01). Participants’ baseline SSB intake had no association with baseline BMI and was not predictive of percent weight loss during treatment (p=0.21). However, over the course of the weight loss program, participants significantly reduced their SSB intake by approximately 7 ounces/week on average (p<0.03). Although this study is not a rigorous randomized trial, these results do support the idea that minimizing SSB consumption is an effective weight loss strategy (and, by extension, that discouraging SSB consumption via a soda tax may improve public health more generally.)

Relationships Between A1C, Insulin Resistance, and Degree of Weight Loss in an Ethnically Diverse Population with Obesity in a Lifestyle Modification Program

J Shaw, PhD; P McMorrow; E Pinkasavage; C Hopkins; R Berkowitz, MD; N Alamuddin, MD; Z Bakizada; T Wadden, PhD; RPearl, PhD; A Chao, PhD; N Alfaris, MD

This study assessed the effect of different magnitudes of weight loss (<5%, 5-9.9%, >10%) on insulin resistance and A1c levels in a largely African-American sample of adults (n=102) with obesity but not diabetes. Subjects participated in a 14-week group lifestyle modification program with weekly 90-minute sessions, prescribed a 1000-1200 calorie/day portion-controlled diet, and were encouraged to gradually increase physical activity to 175 minutes a week. Participants lost on average 8.4% of their baseline weight. Greater weight loss was associated with greater improvements in A1c (p=0.04) with mean changes of +0.03, -0.07, and -0.15 with weight loss <5% (n=17), 5-9.9% (n=52), and >10% (n=33), respectively. Changes in insulin levels for the three groups were +0.3, -2.1, and -3.7, respectively. The association between greater categorical weight loss and improvements in A1c and insulin sensitivity have been previously reported in predominantly white samples, and this study importantly confirms that the same is true among African Americans.

Association Between Expanded Normal Weight Obesity and Insulin Resistance among U.S. Adults in the National Health and Nutrition Examination Survey (NHANES)

K Martinez; L Tucker, PhD; L Davidson, PhD; B Bailey, PhD; J LeCheminant, PhD

This cross-sectional study expanded the evaluation of normal weight obesity (NWO) – a condition in which individuals are classified as normal weight by BMI but have excess body fat – and its association with insulin resistance using a nationally representative sample of US adults without diabetes (n=5,983). BMI, body fat percentage, and HOMA-IR data were acquired from the 1999-2006 NHANES data set.  Among NWO subjects, BMI averaged 27.9 kg/m2 for women and 27.8 kg/m2 for men, with respective body fat percentages of 40.5% and 27.8%. HOMA-IR levels were 2.04 for women and 2.47 f0r men. Insulin resistance increased incrementally per BMI levels primarily and body fat levels secondarily. For example, individuals in the overweight-low body fat category had significantly higher HOMA-IR levels than those in the normal weight-high body fat category. The cross-sectional nature of the study did not allow for the causality of the relationship between insulin resistance, BMI, and body fat percentage to be determined, but did conclude that both high BMI and high body fat percentage appear to be strongly related to insulin resistance. Due to the costs associated with precisely measuring body fat and the accuracy of measuring BMI independently, the researchers recommended that BMI continue to be used in its standard form to predict insulin resistance.

Exhibit Hall

AlterG

AlterG’s relatively minimalistic booth highlighted its centerpiece: the anti-gravity treadmill, which, bottom line, is very cool. The booth itself was difficult to locate, and almost symbolic of AlterG’s recent foray into the world of obesity care. Our conversation with the booth representatives told a narrative of an initial target market of professional athletes for the anti-gravity treadmill. The company then expanded to the world of physical therapy, and around 2010, this expanded once more to providing a resource for people with obesity. “All of the gain, none of the pain” was the slogan of choice, and we were delighted to have the opportunity to test this for ourselves.  The treadmill, markedly larger than a conventional treadmill, had all of its familiar staples – the start/stop buttons, the settings for speed, and the settings for incline percentage. (Yeah, we do this in our office.) The distinguishing factor was the setting that adjusted the percentage of the user’s body weight. Prior to stepping onto the machine, the user put on a pair of compression shorts called a “skirt” that served to form an airtight seal with the treadmill apparatus. It operated on the principle creating an air pressure differential – the higher the air pressure levels within the seal, the lighter the user would feel. (AlterG’s technology allows users to unload up to 80% of their weight – roughly equivalent to the weight one would experience on the moon!) During the test run, there was a discernible difference in weight-bearing, as lower weight percentage settings decreased the load on joints and tendons to the extent that it made higher speeds and inclines much easier. After the test run, we were pleasantly surprised to find that the most information-dense pamphlet was a packet that summarized the clinical research involving the anti-gravity treadmill. Although most of these studies were not nearly as large or as comprehensive as conventional clinical trials (but who cares!), we remain optimistic that this innovative treadmill will eliminate many of the barriers that impede adherence to physical activity programs in individuals with obesity, and provide an avenue through which patients can gradually gain self-confidence about exercise in a less physically-taxing way.

Eisai

Eisai displayed a large booth adorned with its classic red, white, and blue color scheme. Signage was dedicated to both Belviq (lorcaserin) and the recently released once-daily version, Belviq XR (lorcaserin extended-release). On one side, the booth featured tall touch screen displays with information on the drug’s clinical data, safety information, and patient support programs. In addition, pamphlets outlining drug details as well as reimbursement details with the company’s savings card were dispersed throughout the booth. Warmly welcoming representatives were more than happy to share information on Belviq and Belviq XR, also offering delicious healthy smoothies . On the other side of the booth, representatives sat behind a bar to answer any more specific questions about Eisai’s portfolio of obesity products.

Ethicon

Johnson & Johnson’s Ethicon had an impressively large and interactive booth. Underneath a revolving header inscribed with the Ethicon logo, representatives displayed the company’s line of products, headlined by an assortment of suture-assistant devices. A separate area of the booth was dedicated to Johnson & Johnson’s 7 Minute Workout App, giving attendees (and Close Concerns associates!) an opportunity to try out some of the app’s suggested short workouts as a respite from sitting in oral presentations all morning. Kelly’s family follows this app at home and loves it. We also refreshed ourselves with hydrating glasses of fruit-infused water and energizing freshly-made oat bars. Ethicon’s booth certainly emulated the company’s goal of shaping the future of surgery and creating innovative solutions in health care. This was further evidenced by a series of Ethicon-sponsored presentations over the course of Obesity Week on current and new approaches to the duodenal switch, building the successful and thriving bariatric program, and the potential of bundled payments resulting in increased bariatric surgery, all of which drew large audiences.

Medtronic

In contrast to Medtronic’s diabetes product line, the line of products displayed at Obesity Week’s exhibit hall was geared towards largely toward bariatric surgeons. The simple slogan, “Take a stand against obesity” sought to appeal to the surgeons’ role in dramatically improving patient outcomes through bariatric surgery. We’d love if this slogan could be a bit more broadly interpreted – c’mon, management, we’re counting on you! For example, one of Medtronic’s featured products, the ReliaTack articulating reloadable fixation device, claimed “superior access, stronger fixation, and lower cost of care.” With regards to reducing cost, the device accompanied the ReliaTack line of reloadable tacks, which dramatically increased the reusability of the tacking tool without requiring the purchase of a new tool after a limited number of tacks. This seemingly intuitive feature is again indicative of a growing trend of cost-effective quality of care, this time from the provider perspective. While we look sort of forward to learning more about Medtronic’s line of bariatric surgery devices in future conferences, we also look forward to learning how they are going to address obesity at a population level. The company is certainly a giant in the diabetes arena and it needs to generate similar success in the realm of obesity.

Novo Nordisk

Unsurprisingly, Novo Nordisk dominated the exhibit hall, featuring two front-and-center booths each with an enthusiastic crowd of visitors.  One booth at the very entrance – by far the biggest display in the exhibit hall – was dedicated entirely to Saxenda (liraglutide 3.0 mg). On its hanging posters, the booth boasted that Saxenda is “the first and only GLP-1 agonist” approved for chronic weight management with its ad featuring a woman holding up a pair of old larger jeans that are inscribed with “excess weight,” “high cholesterol,” “large waistline,” and “high blood pressure” (hinting toward the drug’s improvement in comorbidities). In the background, a video played discussing the “science of Saxenda,” and the mechanism by which GLP-1 receptors act. “It’s not about the will” to lose weight, the video explained, “it’s about having a way.” A second large both in the center of the exhibit hall was decorated in Novo Nordisk’s classic blue color scheme featuring a sign urging visitors to “rethink obesity.” Another display showed a diagram of the human body, indicating that obesity’s comorbidities affect nearly every organ system, and that even modest 5-10% weight loss can significantly reduce the risk of such comorbidities. The booth further featured a tea bar accompanied by an array of healthy snacks – a welcome change from the sugary fare found in most conference exhibit halls.  The company’s commitment to obesity is clear, and we hope Saxenda’s continued high revenues can reinvigorate the stagnant obesity market and convince payers of the value of obesity pharmacotherapies.

Orexigen

Orexigen’s small booth contained a table with two sales representatives available to speak about the company’s obesity portfolio. The booth was unbranded, with no mention of Contrave (naltrexone/bupropion).

-- by Abigail Dove, Sam Haque, Jennifer Zhao, Helen Gao, Payal Marathe, and Kelly Close