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Combating the global obesity epidemic

  1. Top of page
  2. Combating the global obesity epidemic
  3. The Obesity Society’s 28th Annual Scientific Meeting
  4. Asia-Oceania Conference Preview: April–June 2011
  5. References
  6. Appendix

Currently, obesity is the leading preventable cause of death worldwide and it is viewed as one of if not the most pressing public health epidemics of the 21st century. Individuals who are obese are at a greater risk of developing various diseases, including Type 2 diabetes, cardiovascular disease, sleep apnea, certain types of cancer, osteoarthritis, asthma, erectile dysfunction, and others.1 Moreover, the risk of early death is increased by 30% with every 3.1 kg (6.8 lbs) gained and severely obese individuals tend to die 8–10 years sooner than normal weight individuals.2 One of the major concerns about obesity is the increasing health care expenditures required to treat these individuals. In mid 2010, the Organization for Economic Cooperation and Development (OECD) and the World Health Organization (WHO) released a report that used an economic approach to highlight trends in obesity, causal factors affecting obesity, and effective prevention strategies.2

The first part of the OECD report discusses the alarming increase in the worldwide rate of obesity over the past 30 years, especially as the physical, social, and economic environment continues to present an obesogenic milieu. Before 1980, obesity rates were generally below 10% worldwide, but these rates have doubled or tripled in most countries. In almost half of the OECD countries (Australia, Austria, Belgium, Canada, Chile, Czech Republic, Denmark, Finland, France, Germany, Greece, Hungary, Iceland, Ireland, Israel, Italy, Japan, Korea, Luxembourg, Mexico, Netherlands, New Zealand, Norway, Poland, Portugal, Slovak Republic, Slovenia, Spain, Sweden, Switzerland, Turkey, UK, and US), 50% or more of the population is now overweight. Overall, the increasing obesity epidemic has developed as a result of multiple factors that have made lasting changes in people’s lifestyles. One commonly discussed factor is the increasing supply and availability of food and the shift from traditional meals prepared with raw ingredients to fast food. Compounding this change in diet are general decreases in levels of physical activity.

Although the obesity trends do provide a great deal of data to describe the current situation, the more interesting part of the OECD report looks at what can be done to stem this epidemic. The authors first discuss the role that governments can take to improve health-related behaviors.

It will be important for governments to either increase the availability of new healthy dietary and lifestyle options or to make existing healthy options more affordable and accessible. At least in the OECD countries, several governments have tried to promote a culture of living a healthy life through school programs or changes in health systems. For example, programs targeting school-age children are designed to educate them about healthy lifestyles through healthier school lunches and increased physical activity. With health systems, there have been steps to widely disseminate information about nutrition guidelines and active lifestyles. What will be particularly important as we move forward are policy changes in the food and beverage industry that affect food product formulations and provide information about food contents.

The report moves on to discuss which interventions have been shown to be successful and effective. Interventions tackling obesity tend to fall into three areas: (i) health education and promotion; (ii) regulation and fiscal measures; and (iii) counseling in primary care. If these measures are combined into a comprehensive prevention strategy, it is estimated that the price of countering obesity would be as low as US$12 per capita in Mexico, US$19 per capita in Japan and England, US$22 per capita in Italy, and US$32 per capita in Canada. Furthermore, these programs are estimated to prevent 55 000 deaths from chronic disease in Mexico, 155 000 deaths in Japan, 70 000 deaths in England, 75 000 deaths in Italy, and 40 000 deaths in Canada. Interestingly, the report highlighted that individual counseling by primary care physicians was the most effective preventative measure, but it was also the most expensive. One thing to keep in mind with these preventative strategies is that it may not necessarily reduce healthcare expenditures because people will be living longer. Yet, there should be improved population health, longevity, and quality of life.

Although the OECD report focused almost exclusively on obesity rates in Western countries, the obesity epidemic is also concerning in Asia, where globalization, population movements, technology transfers, economic growth, and East–West exchanges have promoted the adoption of a more Western diet and lifestyle.3 Although the percentage of the population that is overweight or obese in Asian countries is generally lower than that in Western countries, the prevalence of diabetes in most Asian countries (including China, Korea, Singapore, Taiwan, and Thailand) is similar to or higher than the prevalence

rates in Western countries.2,4,5 Such trends indicate that the risks for Type 2 diabetes begin at a lower body mass index (BMI) cut-off for Asians. In fact, a recent study by Palaniappan et al. found a significantly higher prevalence rate of metabolic syndrome among Asian Indian, Chinese, Filipino, Japanese, Korean and Vietnamese

individuals than non-Hispanic White individuals in every BMI category.6 With these apparent differences in the pathophysiological manifestation of Type 2 diabetes between those of Asian and European descent, the prospects of soaring obesity rates in Asia, which will likely accompany the rapid economic development in this region in the coming decades, is alarming, at best. It is clear that tremendous efforts will need to be made in Asia to stem both the obesity and diabetes epidemics in the near future, not only through the implementation of effective and comprehensive prevention strategies, such as those outlined above, but also through increased investment and research into improved diagnostic tools, therapies, and treatment strategies aimed specifically at Asian populations.

The Obesity Society’s 28th Annual Scientific Meeting

  1. Top of page
  2. Combating the global obesity epidemic
  3. The Obesity Society’s 28th Annual Scientific Meeting
  4. Asia-Oceania Conference Preview: April–June 2011
  5. References
  6. Appendix

Shortly after the publication of the OECD’s report on obesity, we attended The Obesity Society’s 28th Annual Scientific Meeting, held 8–12 October 2010 in San Diego, California (http://www.obesity.org/obesity2010/abstracts.asp, accessed September 2010). Every year, The Obesity Society’s meeting is one of the more important and well-attended obesity conferences worldwide, and this year was no different. At the meeting we had the opportunity to learn from a number of leading experts on a variety of topics, including obesity prevention, weight loss drug development, bariatric surgery, nutrition, and public policy. Below we present some of our top highlights.

Aila Rissanen, MD, PhD (Helsinki University Central Hospital, Helsinki, Finland), presented new data on the effects of Novo Nordisk’s glucagonlike peptide-1 (GLP-1) agonist liraglutide (Victoza) on the prevalence of prediabetes and metabolic syndrome in obese adults without Type 2 diabetes over 104 weeks. Study participants (n = 564) were randomized to one of six arms: orlistat 120 mg t.i.d.; placebo; liraglutide 1.2 mg; liraglutide 1.8 mg; liraglutide 2.4 mg; or liraglutide 3.0 mg. The inclusion criteria required participants to have a BMI between 30 and 40 kg/m2, a stable body weight, and fasting plasma glucose (FPG) <126 mg/dL (i.e. non-diabetic). At 52 weeks, patients on all doses of liraglutide and placebo were switched to the 2.4 mg dose, the most efficacious dose of the drug with regard to weight loss (those on orlistat continued treatment with orlistat for the duration of the trial). However, after analysis of the initial 52-week data, the 3.0 mg dose of liraglutide was determined to provide the greatest reductions in weight. Consequently, patients on the 2.4 mg dose were subsequently switched to the 3.0 mg dose for the remainder of the trial. After 104 weeks, there was a considerable decline in the prevalence of metabolic syndrome across all treatment groups: orlistat (38% prevalence of metabolic syndrome at baseline vs. 20% at week 104), placebo (51% vs. 21%), liraglutide 1.2 mg (42% vs. 22%), liraglutide 1.8 mg (36% vs. 15%), liraglutide 2.4 mg (37% vs. 16%), and liraglutide 3.0 mg (42% vs. 16%). The prevalence of prediabetes also fell significantly with liraglutide treatment: orlistat (29% prevalence of prediabetes at baseline vs. 32% at week 104), placebo (33% vs. 24%), liraglutide 1.2 mg (31% vs. 22%), liraglutide 1.8 mg (30% vs. 14%), liraglutide 2.4 mg (34% vs. 16%), and liraglutide 3.0 mg (29% vs. 16%). Notably, those in the orlistat group experienced a 14% increase in the prevalence of diabetes; we assume this is due to the fact that diabetes is a progressive disease, although it makes us wonder about the impact of orlistat on β-cells. Of the patients with prediabetes at baseline (approximately one-third of the population), a sizable 63% of the liraglutide 2.4 mg and 3.0 mg patients (n = 51) had normalized their glycemic control after 104 weeks. Of the remaining 37% of these liraglutide-treated patients with prediabetes at baseline, 35% continued to have prediabetes at week 104 and 2% progressed to diabetes. Liraglutide demonstrated a marked improvement over orlistat (n = 22), with 32% of patients normalizing their glucose and 68% remaining prediabetic (the percentage going to diabetes was zero). Of those with normoglycemia at baseline, 7% of liraglutide 2.4 mg/3.0 mg-treated patients progressed to prediabetes, compared with 17% of orlistat-treated patients. (All numbers are based on the intent-to-treat (ITT) population with last observation carried forward (LOCF) analysis.) Dr Raissanen briefly presented data on adverse events. Approximately 6% of patients in both the orlistat and placebo groups experienced serious adverse events, compared with 10%, 11%, 8% and 11% in the 1.2, 1.8, 2.4, and 3.0 mg liraglutide-treated groups, respectively. The percentage of patients withdrawing from the study due to adverse events tended to increase with dose (3% with orlistat, 6% for placebo, 8% for liraglutide 1.2 mg, 13% for liraglutide 1.8 mg, 14% for liraglutide 2.4 mg, and 10% for liraglutide 3.0 mg). Not surprisingly, gastrointestinal (GI)-related adverse events were the most commonly reported with liraglutide, with significantly higher rates of nausea and vomiting for all doses of the GLP-1 agonist than with placebo or orlistat. There were no major hypoglycemic episodes requiring third-party intervention and no confirmed cases of FPG <56 mg/dL for any treatment.

In a separate poster presentation, Michael Lean, MD (University of Glasgow, Glasgow, UK), presented the weight loss results from the above study on liraglutide. Weight loss was significantly greater for patients receiving liraglutide 2.4/3.0 mg than for patients receiving orlistat. Using ANCOVA analysis on the ITT population with LOCF from randomization, patients receiving liraglutide 2.4/3.0 mg reached an estimated average of 5.3 kg (11.7 lbs) weight loss compared with an estimated average of 2.3 kg (5.1 lbs) weight loss with orlistat (P < 0.001). Using similar analyses on the completer population from screening, including 2 weeks run in period with lifestyle changes, patients on liraglutide 2.4/3.0 mg lost an estimated average of 7.8 kg (17.2 lbs), whereas those on orlistat lost 5.4 kg (11.9 lbs) on average (P = 0.09).

Using observed values (ITT but not LOCF), at the end of 104 weeks those on orlistat lost an average of 6.7 kg (14.8 lbs), whereas those originally assigned to placebo lost an average of 9.4 kg (20.7 lbs) and those originally assigned to liraglutide 1.2, 1.8, 2.4, and 3.0 mg experienced average weight losses of 8.8 kg (19.4 lbs), 9.9 kg (21.8 lbs), 9.4 kg (20.7 lbs), and 10.3 kg (22.7 lbs) from baseline, respectively (baseline weights were not provided). Although the placebo weight loss looks high at first glance, as a reminder these patients were switched to liraglutide at 52 weeks. This enabled the gathering of additional safety data on the high doses of liraglutide (for those originally in the placebo group) and also showed that weight loss seen in active treatment groups from randomization could be repeated when liraglutide was used to “replace” placebo starting at week 52. The percentage of patients achieving 5% and 10% reductions in weight at the two-year mark was also significantly higher for patients receiving liraglutide 2.4/3.0 mg compared with patients receiving orlistat. Using logistic regression analyses on the ITT population with LOCF from randomization, 52% of patients on liraglutide 2.4/3.0 mg lost at least 5% of body weight, whereas only 29% of those on orlistat lost over 5% in body weight (P < 0.001); 26% of patients on liraglutide 2.4/3.0 mg experienced at least 10% weight loss, compared with 16% of patients on orlistat (P = 0.04). We certainly see the results from this trial as a major positive for liraglutide (and likely the GLP-1 class as a whole); the drug now appears to hold promise not only as a treatment for Type 2 diabetes, positioning liraglutide as a powerful tool with which to address both the diabetes and obesity epidemics. We hope future studies will confirm these findings and encourage companies to work with regulatory agencies to create official prediabetes and weight loss indications for currently available and future GLP-1 agonists.

Also in the poster session, Corby Martin, PhD (Pennington Biomedical Research Center, Baton Rouge, Louisiana), discussed results from a double-blind randomized trial that sought to elucidate whether lorcaserin (Arena Pharmaceutical’s 5-HT2c receptor agonist under development as a weight loss therapy) mediates weight loss by reducing energy intake and appetite. Overweight and obese adults were randomized to receive placebo (n = 28) or 10 mg lorcaserin twice daily (n = 29) for 56 days. In the first 7 days of the study, weight maintenance was imposed on all study participants. Beginning on day 8, all participants began targeting a 600 kcal/day energy deficit through a standardized diet and exercise plan. Food intake was measured in the laboratory at lunch and dinner after an overnight fast. Furthermore, ratings of appetite were measured using the Eating Inventory. At baseline, the average age was approximately 49 years, body weight was 101.3 kg (23.4 lbs) in the placebo arm and 96.7 kg (213.2 lbs) in the lorcaserin arm, and average BMI was approximately 35 kg/m2. Participants in the lorcaserin arm achieved significantly greater weight loss than those in the control arm at the end of the study. Patients treated with lorcaserin averaged 3.7 kg (8.1 lbs) weight loss, whereas individuals treated with placebo averaged 2.2 kg (4.8 lbs) weight loss (P < 0.01). We note that much of the difference in weight loss between the groups was attributable to differences in fat-free mass. Lorcaserin was also found to significantly decrease energy intake and appetite ratings compared with placebo. After 7 days, the period in which weight maintenance was enforced, while food/energy intake was observed to decrease in both groups, the reduction in food intake was significantly greater in lorcaserin-treated patients (470 kcal) than in placebo-treated subjects (205 kcal; P < 0.01). Appetite/prospective food eating was also significantly decreased over the 56-day study in the lorcaserin group, as determined by the Eating Inventory (P < 0.05). Thus, the investigators concluded that lorcaserin reduces weight primarily through its effects on energy intake and appetite. On 22 October 2010, Arena received a complete response letter from the US Food and Drug Administration (FDA) for lorcaserin (see http://invest.arenapharm.com/releasedetail.cfm?ReleaseID=521977, accessed October 2010), delaying the drug candidate’s approval in the US. The agency’s concerns included the unknown implications of mammary masses in female rats, the exposure–response relationship for mammary adenocarcinomas, and the unclear mechanism of action and safety margin for lorcaserin-related brain astrocytomas. Arena is preparing to file lorcaserin in the European Union in 2011.

Robert Kushner, MD (Northwestern University Feinberg School of Medicine, Chicago, Illinois), presented on the use of bariatric surgery as a weight loss tool. He first provided an overview of the four bariatric procedures currently performed in the US: (i) lap adjustable gastric band surgery (LAGB); (ii) gastric sleeve surgery (GS); (iii) Roux-en-Y gastric bypass (RYGB); and (iv) bilial pancreatic diversion (BPD). Historically, RYGB has been the gold standard, although LAGB is gaining traction. RYGB has considerable impact on the GI tract, requiring two anastomoses and resulting in stomach division and decreased micronutrient uptake. In contrast, LAGB has minimal impact on the GI tract, with minimal trauma and no effect on micronutrient absorption, as well as being reversible surgery. However, LAGB surgery introduces the possibility of slippage leaks and infections. Meanwhile, RYGB remains the preferred method of bariatric surgery for patients with diabetes because of its effects on neuromodulation and gut hormone levels. Dr Kusher next detailed the efficacy of bariatric surgery for weight loss, as well as for its related comorbidities. In a meta-analysis performed by O’Brien et al. in 2006, RYGB, LAGB, and BPD all led to 50% or greater reductions in excess weight, sustained at 10 years after the operation.7 Patients who undergo RYGB tend to experience more rapid weight loss, whereas patients who undergo LAGB tend to experience more gradual weight loss (both result in an average long-term reduction in excess weight of 50%–60%). Furthermore, bariatric surgery also leads to improvements and resolution in Type 2 diabetes, hypertension, hyperlipidemia, and sleep apnea.8 In a study by Schauer et al. in 2003, patients with Type 2 diabetes who underwent bariatric surgery decreased insulin and oral antidiabetic medication use by approximately 80%.9 However, Dr Kusher pointed out that some bariatric procedures result in the malabsorption of micronutrients. Specifically, RYGB and BPD cause malabsorption of thiamine, iron, vitamin B12, folate, calcium, and vitamin D (BPD also leads to malabsorption of macronutrients). Hence, patients who undergo these procedures must take vitamin and mineral supplements for the rest of their lives. As Dr Kushner stressed, physicians should always ask patients who have undergone bariatric surgery what supplements they are taking, because moderate micronutrient deficiencies often have no clear clinical manifestations. Finally, Dr Kushner emphasized the importance of care and monitoring after surgery. As he noted, surgery is only the first step and the hard work begins after discharge. Improvements seen at the 1- or 2-year mark may not be durable or permanent, so primary care physicians need to have long-term follow-ups with their patients. More specifically, healthcare professionals should engage proactively in the identification and management of postoperative complications, comorbidities, and nutritional deficiencies while providing lifestyle and dietary counseling and support as needed. In conclusion, Dr Kushner asserted that bariatric surgery is not a cure for obesity and patients who undergo these procedures require life-long care. Hence, physicians must be attentive to their patients and become familiar with medical and nutritional complications that may arise.

John Jakicic, PhD (University of Pittsburgh, Pittsburgh, Pennsylvania), reported on the 4-year changes in fitness and physical activity between patients with Type 2 diabetes randomized to receive intensive lifestyle intervention (ILI) or standard diabetes support and education (DSE) in the Look Ahead Trial, as well as the effects of these therapy regimens on changes in glucose control (A1c). In this study, 5145 people with Type 2 diabetes were randomized to receive ILI (n = 2575) or DSE (n = 2570). All participants had to undergo a maximal exercise test before entry into the study and all participants received 1 h of diabetes education at the beginning of the study. Participants assigned to DSE subsequently received three group education sessions over the 4-year study period, whereas ILI participants targeted 7% weight loss, 175 min moderate-intensity physical activity per week, and received a dietary intervention involving portion control (liquid meal replacements or structured meal plans). The 4-year weight change, change in physical activity, and change in fitness were significantly different between the DSE and ILI groups. At 4 years, DSE participants experienced an approximate 1.0 kg (2.2 lbs) weight loss, whereas ILI participants lost an average 4.5 kg (9.9 lbs). At the 1-year mark, ILI participants increased energy expenditure by 871 kcal/week, compared with 107 kcal/week in DSE participants. At the 4-year mark, ILI participants only had increased energy expenditure from baseline by 349 kcal/week, compared with 104 kcal/week in the DSE group. The percentage increase in fitness was significantly higher in the ILI group than in the DSE group, even after adjusting for weight change and baseline maximal exercise test scores (METS). In both groups, participants who lost more weight had greater improvements in fitness and physical activity. At 4 years, A1c reduction from baseline was significant in both the DSE and the ILI arms for patients with a 10% or greater increase in fitness from baseline. On average, these participants experienced an approximate 0.30% reduction in A1c from baseline. Adjusted for age, gender, weight change, and diabetes medications, the A1c reduction was no longer significant in the ILI group, but remained significant in the DSE group for those who improved fitness. Dr Jakicic concluded by urging audience members not to disregard fitness as a way of improving outcomes for people with Type 2 diabetes.

After arguing that increased caloric intake (as opposed to inactivity) accounts for most cases of obesity, the highly regarded George Bray, MD (Pennington Biomedical Research Center, Baton Rouge, Louisiana), explored whether soft drinks are related to obesity, whether they are related to disease, and the potential mechanisms by which they act, with a focus on fructose. Dr Bray asserted that soft drink consumption is, indeed, related to obesity and disease. In a meta-analysis conducted by Olsen and Heitmann in 2009, soft drink intake was associated with weight gain and diabetes.10 In another study, soft drink consumption predicted increases in energy intake and body weight.11 In a meta-analysis by Malik et al., increased soft drink consumption increased the risk of cardiometabolic disease:12 the group with the highest soft drink consumption was shown to have a 24% higher risk of cardiometabolic disease than the group with the lowest soft drink consumption. Plausible mechanisms by which soft drink consumption could contribute to obesity and disease offered by Dr Bray included increased caloric intake (and the subsequent failure to compensate for these calories) and the effects of fructose. The effects of fructose consumption are markedly different than the effects of glucose consumption. Cohen and Schall demonstrated in 1988 that fructose consumption leads to smaller rises in insulin, smaller rises in leptin, greater rises in energy expenditure, and greater rises in triglycerides than glucose consumption.13 In addition, Brown et al. showed that fructose consumption is associated with rises in blood pressure, pulse rate, and the respiratory exchange ratio.14 In another study, Raben et al. demonstrated that sucrose (compared with aspartame) increased body weight, triglycerides, and various inflammatory markers.15 Furthermore, Stanhope et al. showed that fructose increases visceral fat and de novo lipogenesis.16 Finally, Johnson et al. demonstrated that fructose (but not glucose) increases uric acid production in the liver.17 Dr Bray recommended for people to focus on obtaining fructose from good sources (fruits, vegetables, dairy, and grains) instead of from bad sources (sugar, soft drinks, fruit drinks, and sweets). Notably, Dr Bray proposed for fructose to be added to food labels. In order to address the broader issue of excessive soda consumption, he suggested that we: (i) conduct clinical trials to demonstrate the benefit of reducing soft drink consumption; (ii) raise greater awareness of the problem; (iii) increase the availability of alternatives; (iv) garner cooperation from industry; and (v) encourage government action.

Christopher Gardner, PhD (Stanford University, Stanford, California), drew a few conclusions about diets, diet studies, and their limitations after reviewing a number of studies: (i) low-fat diets have not been proven to be superior in recent trials; (ii) low-carbohydrate diets have consistently demonstrated comparable efficacy for weight loss; (iii) low-carbohydrate diets are by nature higher in protein and fat; (iv) average weight loss for all diets in the A to Z study was modest after 1–2 years;18 (v) long-term adherence to diets is typically poor; (vi) studies on diets are all relatively short (often too short for weight stabilization); and (vii) there are many inherent challenges involved in conducting successful weight loss studies. Traditional low-fat diets may be particularly ineffective for weight loss in people with insulin resistance. Consistent with findings from a study by Ebbeling et al.,19 in which weight loss was minimal for insulin resistant subjects on low-fat diets, Dr Gardner came to the same conclusion after conducting an exploratory analysis on data from his own A to Z study,20,21 which included the Ornish (low-fat, high-carbohydrate) and Atkins (low-carbohydrate) diets. Interestingly, preliminary evidence suggests a simple DNA test could help dieters predict whether a low-fat diet or a low-carbohydrate diet would be more appropriate for them. A group that reviewed 200 potential genes related to weight loss approached Dr Gardner and his colleagues wanting to investigate whether a set of multi-loci genotypes they identified had predictive value in how effective low-carbohydrate and low-fat diets would be for each study participant. Of 121 subjects from which cheek swabs were obtained, the group predicted that approximately 40% of subjects would do better on low-carbohydrate diets (n = 50), 40% would do better on low-fat diets (n = 48), and 20% would not do well on either diet (n = 23). Strikingly, those who were properly assigned to the correct diet (Ornish for the low-fat genotype and Atkins for the low-carbohydrate genotype) lost, on average, 6.0 kg (13 lbs) more weight than those who were improperly assigned over the duration of the study.21 Although the numbers from the study are small, the data suggest that incredible heterogeneity in genetic predispositions exists, a presumably important factor that should be taken into consideration when choosing diets.

Finally, Robert Kushner, MD (Northwestern University Feinberg School of Medicine, Chicago, Illinois), reviewed the clinical guidelines for and the current state of obesity management. He recommended clinicians screen all adult patients for obesity and offer intensive counseling and behavioral interventions to promote sustained weight loss in obese patients. He referenced a report from the new Surgeon General entitled The Surgeon General’s Vision for a Healthy and Fit Nation 2010, which outlines a blueprint for communities to effectively combat the obesity epidemic.22 Moving to the clinical management of obesity, Dr Kushner highlighted several statistics that demonstrate the need for more communication between physicians and patients on the benefits of maintaining a healthy weight. He noted that from 1995 to 2004, 6% of office visits involved a discussion relating to weight and 24% involved a discussion relating to living a healthy lifestyle in general.23 He was particularly worried that the proportion of office visits pertaining to weight and healthy living remained relatively flat over this 9-year period. Dr Kushner referred to this phenomenon as a “gap in counseling”, given that 66% of US adults are either overweight or obese. Therefore, he urged clinicians to use all the available resources, including, but not limited to, patient handouts, pedometers, and electronic medical records.

Asia-Oceania Conference Preview: April–June 2011

  1. Top of page
  2. Combating the global obesity epidemic
  3. The Obesity Society’s 28th Annual Scientific Meeting
  4. Asia-Oceania Conference Preview: April–June 2011
  5. References
  6. Appendix

10–11 May 2011, Tokyo, Japan: The 5th Annual Conference in Japan for Asian New Drug Development (http://www.diahome.org/DIAHome/Education/FindEducationalOffering.aspx?productID=24457&eventType=Meeting)

Leading members of pharmaceutical companies and regulatory agencies from China, the Republic of Korea, Chinese Taipei, and Japan will again convene to discuss issues and share experiences regarding drug development in Asia. Although prevention strategies will remain paramount to overcoming the increasing burden of chronic diseases in these populations, such meetings hold great importance for bringing needed therapeutics and medical devices to Asian patients in a safe and efficient manner. This is particularly true for the diabetes arena. Although the International Diabetes Foundation has estimated that the number of individuals with diabetes worldwide will increase from 240 million in 2007 to 380 million in 2025, more than 60% of the total diabetes population in 2025 is predicted to be Asian.3 Given the ever-growing and important nature of these markets for antidiabetic therapies, as well as the movement of several prominent diabetes pharmaceutical and device companies into these Asian markets already, we look forward to hearing any insights provided on how treatments can be best delivered to these Asian populations. Although the agenda has not yet been confirmed, program chairs Hirnobu Saito, PhD (Daiichi Sankyo, Tokyo, Japan), Herng-Der Chern, MD, PhD (Center for Drug Evaluation, Taipei, Taiwan), Yil-Seob Lee, MD, PhD, MBA (GlaxoSmithKline, Seoul, Republic of Korea), and Ling Su, PhD (Novartis, Shanghai, China), will lead discussions on several topics related to diabetes drug development, including safety reporting, pharmacovigilance, good clinical practice (GCP) compliance and inspection, and pharmacogenomics.

19–21 May 2011, Sapporo, Japan: The 54th Annual Meeting of the Japan Diabetes Society (http://www2.convention.co.jp/jds54/greeting/index_en.html)

With an overarching theme of Diabetes and its Complications: Prospects for Overcoming the Disease, healthcare professionals and scientists from the Asia Pacific region will gather at the 2011 meeting of the Japan Diabetes Society to discuss the future of diabetes care. Although the itinerary has not yet been posted, central to the meeting will be the recent discovery of incretin-based therapies, which have demonstrated an ability to not only control blood glucose levels, but also potentially protect β-cells from degeneration. In order to overcome diabetes and its complications, sessions at the meeting will focus on the need to move towards therapies that provide therapeutic benefits beyond glycemic control, especially with regard to slowing or reversing β-cell degeneration, one of the underlying causes of Type 2 diabetes.

References

  1. Top of page
  2. Combating the global obesity epidemic
  3. The Obesity Society’s 28th Annual Scientific Meeting
  4. Asia-Oceania Conference Preview: April–June 2011
  5. References
  6. Appendix
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    Ebbeling CB, Leidig MM, Feldman HA, et al. Effects of low-glycemic load vs low-fat diet in obese young adults. JAMA. 2007; 297: 2092102.
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    Gardner CD, Kiazand E, Alhassan S, et al. Comparison of the Atkins, Zone, Ornish, and LEARN diets for change in weight and related risk factors among overweight postmenopausal women. JAMA. 2007; 297: 96977.
  • 21
    Gardner CD. Diet as a treatment. Proceedings of The Obesity Society 28th Annual Scientific Meeting, 8–12 October 2010, San Diego, CA, USA.
  • 22
    US Department of Health and Human Services. The Surgeon General’s Vision for a Healthy and Fit Nation 2010. US Department of Health and Human Services, Office of the Surgeon General, Rockville, MD, 2010.
  • 23
    McAlpine DD, Wilson AR. Trends in obesity-related counseling in primary care: 1995–2007. Primary Care. 2007; 45: 32229.
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    James WP, Caterson SD, Coutinho W, et al. Effects of sibutramine on cardiovascular outcomes in overweight and obese subjects. New Engl J Med. 2010; 363: 9724.
  • 25
    Blevins TC, Bode BW, Carg SK, et al. American Association of Clinical Endocrinologists Continuous Glucose Monitoring Task Force. Endocr Pract. 2010; 16: 73045.

Appendix

  1. Top of page
  2. Combating the global obesity epidemic
  3. The Obesity Society’s 28th Annual Scientific Meeting
  4. Asia-Oceania Conference Preview: April–June 2011
  5. References
  6. Appendix

Company Updates

September 13:Novo Nordisk reported plans to double its research and development workforce in China from its current 100 employees to 200 by 2015. Most of this expansion will go towards a new Diabetes Research Unit, which will focus on novel biopharmaceutical therapies.
September 17:Transition Therapeutics announced the termination of its entire gastrin analog program, which included TT-223 (in development with Eli Lilly for the treatment of Type 2 diabetes), as well as several longer-acting preclinical candidates.
September 30:Sanofi-aventis released promising initial results from the Phase 3 program for lixisenatide, the company’s GLP-1 agonist candidate. In the GETGOAL-L Asia study (http://en.sanofi-aventis.com/binaries/20100930_GETGOAL_en_tcm28-29296.pdf, accessed September 2010), Asian patients insufficiently controlled on a basal insulin (with or without a sulfonylurea) treated with lixisenatide achieved an average A1c reduction of 0.77% compared with an average 0.11% increase in A1c experienced with placebo after 24 weeks. Results from all 10 Phase 3 trials are expected by the end of 2011. Sanofi-aventis is hoping lixisenatide can be the first GLP-1 agonist with a cardiovascular safety “claim” at its launch in the US (2013, assuming a successful and timely regulatory review). The company plans to file lixisenatide for approval in the European Union and Japan in 2011 and in the US in 2012.
October 8:Abbott announced the withdrawal of the weight loss drug Meridia (sibutramine) from the US market at the request of the US FDA. The decision ended a review process that had started in November 2009, when Abbott provided the FDA with preliminary results of the SCOUT study. As a reminder, the 6-year study showed elevated cardiovascular event risk in patients with prior cardiovascular risk.24
October 13:AT&T and WellDoc formed a partnership to provide mobile health solutions based on WellDoc’s chronic disease-management technology. The two companies plan to jointly market and sell mobile health systems to insurance providers and disease-management organizations, with AT&T also offering application hosting, secure infrastructure, and overhead support to complement WellDoc’s technology platform.
October 13:The American Association of Clinical Endocrinologists (AACE) released consensus statements from key opinion leaders on insulin pump management and continuous glucose monitoring (CGM).25 The authors emphasized the need for good education of patients and physicians, and they discussed the possibility of a certification program for clinicians who are experts in pump use.
October 15:GI Dynamics announced that its GI liner EndoBarrier had received CE mark approval (a mandatory mark certifying that a product meets European Union safety, health, and environmental requirements) for 12 months of treatment in the European Union. As a reminder, on 1 September 2010, GI Dynamics partnered with Elemental Healthcare to launch the EndoBarrier in England, Wales, Scotland, Northern Ireland, and Ireland. As we understand it, GI Dynamics is positioning the EndoBarrier towards Type 2 diabetes patients who are obese (with a BMI between 30 and 50 kg/m2).
October 18:Pfizer entered into an agreement with Biocon to obtain exclusive worldwide rights to commercialize Biocon’s biosimilar insulin program. Biocon will receive US$200 million upfront, US$150 in milestone-related payments, and additional undisclosed payments linked to global sales. Biocon will be responsible for the clinical development, manufacturing, supply, and regulatory approval of its insulin products, whereas Pfizer will be initially focused on commercializing Biocon’s recombinant human insulin, which is already approved in 27 developing markets. Pfizer and Biocon will also seek to clear the regulatory pathways for their biosimilar insulins in the US and European Union as soon as patents expire.
October 19:Amylin received a complete response letter from the FDA for Bydureon (exenatide once-weekly). In the letter (http://phx.corporate-ir.net/phoenix.zhtml?c=101911&p=irol-newsArticle&ID=1484584, accessed October 2010), the FDA requested a thorough QT study (i.e. a cardiovascular study that examines the effects of a drug on the QT interval of an electrocardiogram) of exenatide at supratherapeutic levels to assess cardiovascular risk in patients with renal impairment, as well as data from the recently completed DURATION-5 study. Amylin management conservatively estimated that the company would issue its complete response to the FDA by the end of 2011. Bydureon is still under review by the European Medicines Agency (EMA) and a response is expected sometime in the first half of 2011.
October 20:MacroGenics and Eli Lilly announced that the Phase 3 Protégé Trial of teplizumab (MGA031), an anti-CD3 monoclonal antibody therapy, failed to meet its primary efficacy endpoint, a composite of daily insulin usage and A1c levels after 1 year in recent-onset Type 1 diabetes patients. Owing to this lack of efficacy, the companies have suspended enrollment and dosing in the Phase 3 Protégé Encore Trial as well as the Phase 1b SUBCUE Trial.
October 22:Arena received a complete response letter for lorcaserin, the company’s weight loss drug candidate, from the US FDA (http://invest.arenapharm.com/releasedetail.cfm?ReleaseID=521977, accessed October 2010). The agency’s concerns included the unknown implications of mammary masses in female rats, the exposure–response relationship for mammary adenocarcinomas, and the unclear mechanism of action and safety margin for lorcaserin-related brain astrocytomas. The US FDA also highlighted the “marginal” efficacy of lorcaserin and requested the final BLOOM-DM data. The company remains focused on defining a path forward for lorcaserin (Lorqess) and has scheduled a meeting with the US FDA “before the end of the year”. Arena is preparing to file lorcaserin in the European Union in 2011.
October 26:Phenomix Corporation reported that it was shutting down after Forest Laboratories had stopped funding the development of Phenomix’s lead compound, a once-daily dipeptidyl peptidase-4 inhibitor dutogliptin (PHX1149), in April for “business reasons”. Unable to find another major partner in the intervening months and unable to afford a Phase 3 program with venture capital money alone, Phenomix is now seeking to sell its assets, including dutogliptin and a preclinical therapy for hepatitis C.
October 26:Bristol-Myers Squibb and Astra Zeneca announced that they remain on track to file dapagliflozin, a sodium glucose cotransporter 2 (SGTL-2) inhibitor, in the European Union and US by the end of 2010 or early 2011. Assuming a favorable and timely regulatory review, dapagliflozin may be available as early as 2011.
October 27:Novo Nordisk’s liraglutide (Victoza) had its best quarter on the market, jumping 136% sequentially to DKK 700 million (US$121 million). Novo Nordisk noted that approximately two-thirds of liraglutide sales occurred in the US and that uptake has been strong in Japan since the product was launched in mid 2010. Novo Nordisk now expects liraglutide to achieve blockbuster status (US$1 billion revenue) in 2012, as opposed to previous guidance of 2015, given strong sales and the delay in approval for Amylin/Eli Lilly/Alkermes’s Bydureon. The company looks for potential regulatory approval for Victoza in China in the second half of 2011.
October 27:Novo Nordisk reported preliminary results from Phase 3 studies for its ultralong-acting basal insulin Degludec and its fixed combination Degludec/Novolog insulin product DegludecPlus (http://www.novonordisk.com/include/asp/exe_news_attachment.pdf?sAttachmentGUID=058b7592-98b8-456e-ad06-a3712eccd726, accessed October 2010). In a treat-to-target study, individuals with Type 2 diabetes administered Degludec in a flexible dosing schedule (at intervals between 8 and 40 h) achieved average A1c reductions at 26 weeks similar to those in patients treated with Lantus according to label. However, those in the Degludec arm experienced significantly lower fasting glucose levels than those in the Lantus arm. In a separate study, the safety and efficacy of DegludecPlus was compared with that of NovoMix 30 in individuals with Type 2 diabetes. At 26 weeks, patients in both groups achieved an average A1c reduction of 1.5% from a baseline of 8.6%. Hypoglycemia, particularly nocturnal hypoglycemia, was also significantly reduced in the DegludecPlus arm.
October 28:Vivus received a complete response letter from the US FDA for its obesity drug Qnexa (phentermine/topiramate). The letter requested an assessment of both topiramate’s and Qnexa’s potential risk for teratogenicity, an issue that received significant attention during the Advisory Committee meeting in mid-July, as well as evidence that the increases in heart rate observed in Qnexa-treated patients do not increase the risk for major cardiovascular events. The agency has also requested the final study report of the SEQUEL trial (OB-305), the 52-week extension of the CONQUER study. The company is planning to submit a formal response to the US FDA’s complete response letter by 15 December 2010.
November 1:Biodel announced the receipt of a complete response letter from the US FDA regarding Linjeta, the company’s ultrarapid insulin analog (formerly known as Viaject; http://ir.vivus.com/releasedetail.cfm? ReleaseID=524576, accessed October 2010). The US FDA requested two new Phase 3 trials of the commercial formulation of Linjeta, one in Type 1 diabetics and one in Type 2 diabetics, to demonstrate unequivocal efficacy and more definitive assessments on hypoglycemia and tolerability. In addition, the agency requested further data relating to the stability and manufacturing of Linjeta, as well as the resolution of manufacturing issues related to the recent site inspections at Hyaluron Inc. and Wockhardt Ltd, Biodel plans to either initiate new Phase 3 trials with Linjeta or to advance another formulation into the clinic after meeting with the US FDA, presumably in the first quarter of 2011.
November 4:Ortho-McNeil-Janssen Pharmaceuticals terminated its partnership with Arena Pharmaceuticals to develop APD597, a G-protein-coupled receptor 119 agonist for the treatment for Type 2 diabetes, after the completion of the Phase 1 program for the compound. Although results from the program were not released, Arena management noted that the program demonstrated the potential ability of APD597, both alone and in combination with a DPP-4 inhibitor, to treat Type 2 diabetes. Arena is presumably pursuing other partnership opportunities at this time.
November 5:Bristol-Myers Squibb and Astra Zeneca received approval from the US FDA for Kombiglyze XR, a fixed-dose combination of onglyza and metformin XR. This will be the first once daily fixed-dose combination of a DPP-4 inhibitor and metformin to reach the US market.
November 5:DexCom received responses from the FDA for all three of its products under review at the agency: the fourth-generation continuous glucose monitoring (CGM) sensor, the DexCom/Edwards first-generation IV-based in-hospital CGM, and the DexCom/Insulet combination CGM/pump product. Although the specifics of the FDA’s responses were not disclosed, management noted that “substantial” information was requested for each product, including human clinical data for the DexCom/Insulet product. Regarding the fourth-generation sensor, DexCom plans to submit its clinical trial protocol for FDA confirmation prior to starting the trial and it hopes to submit its next-generation hardware platform along with the amended filing for the fourth-generation sensor in the first half of 2011. The company must still clarify the path forward for the Edwards/DexCom in-hospital CGM.
November 9:Arena announced topline results from the BLOOM-DM trial, which examined the safety and efficacy of lorcaserin (a 5-HT2C receptor agonist under development as a weight loss drug) in overweight and obese patients with Type 2 diabetes (http://invest.arenapharm.com/releasedetail.cfm?ReleaseID=528113, accessed November 2010). Using a modified intent-to-treat analysis, lorcaserin met all three of its primary efficacy endpoints: 5% of lorcaserin-treated patients lost at least 5% of body weight, compared with 16.1% of placebo-treated patients; furthermore, 16.3% of those on lorcaserin achieved at least 10% weight loss, compared with 4.4% of those on placebo. Overall, those on lorcaserin experienced a mean weight loss of 4.5% compared with 1.5% in placebo-treated patients. Despite the modest weight loss, those on lorcaserin experienced a notable 0.9% reduction in A1c compared with a 0.4% reduction in those on placebo.
November 15:Santarus launched Cycloset (bromocriptine mesylate) in the US. Cycloset is a dopamine receptor agonist for the treatment of Type 2 diabetes recently in-licensed by Santarus from S2 Therapeutics and VeroScience.
November 16:Amylin and the Juvenile Diabetes Research Foundation (JDRF) announced their partnership to investigate the use of Metreleptin (Amylin’s leptin analog) as a treatment for Type 1 diabetes in a proof-of-concept Phase 1 trial. Through the agreement, the JDRF and Amylin will provide financial support for the trial, which will be conducted at UT Southwestern. Metreleptin was previously found to improve blood glucose levels, blood fats, and cholesterol levels in animal models of Type 1 diabetes (http://phx.corporate-ir.net/phoenix.zhtml?c=101911&p=irol-newsArticle&ID=1496945, accessed November 2010).