Excellence in Diabetes 2014

February 28 – March 2, 2014; Doha, Qatar Day #1-3 Full Commentary - Draft

Executive Highlights

Hello from the Souk Al Bahar in Dubai, United Arab Emirates where we are reflecting on the lessons learned at the second annual Excellence in Diabetes (EiD) congress. EiD 2014 drew 820 delegates from 29 countries to Doha, Qatar last week. This was a big increase from the 500 attendees at the 2013 meeting in Istanbul, Turkey, though more countries were represented (59) last year. The conference was jointly hosted by EiD 2014’s Steering Committee (including Dr. David Matthews [Oxford University, UK], Dr. John Buse [University of North Carolina, Chapel Hill, NC], Dr. Ele Ferrannini [University of Pisa, Italy], Dr. Pamela Dyson [Churchill Hospital, Oxford, UK], and Dr. Luc Van Gaal [Antwerp University Hospital, Antwerp, Belgium]) and the Gulf Group for the Study of Diabetes (GGSD). Thus, the conference featured notable commentary both on international controversies in diabetes, as well as more detailed discussion of the challenges and opportunities Middle East’s diabetes and obesity epidemics pose. We believe the conference is growing largely due to reputation and renown of the organizers and speakers, and that the attendance was also big in the middle east due to interet in the area.

On the international side, Dr. Buse voiced several uncharacteristically strong opinions at EiD. In the conference’s closing session, Dr. Buse was “interrogated” by attendees on “The Good, The Bad, and The Ugly” of clinical trials in diabetes. In Dr. Buse’s view the two ugliest trials in the history of diabetes were the cardiovascular outcomes trials of Takeda’s alogliptin (Nesina) EXAMINE and AZ’s saxagliptin (Onglyza) SAOVR-TIMI 53 because they were expensive, required a lot of participants, and offered limited meaningful results due to their short duration in a relatively unhealthy population. During a Novo Nordisk symposium he called Novo Nordisk’s Tresiba (insulin degludec) and Victoza (liraglutide) “arguably the two most powerful glucose-lowering agents on Earth.” Furthermore, he thinks IDegLira, the fixed-ratio combination of Tresiba and Victoza, is the “most powerful agent we have even contemplated in type 2 diabetes.” In other highlights on global diabetes care, Dr. John Wilding (University of Liverpool, Liverpool, United Kingdom) suggested that SGLT-2 inhibitors could be renal protective (indeed J&J is currently exploring that with the CREDENCE renal outcomes trial), and Dr. Jens Holst (University of Copenhagen, Denmark) said of liraglutide 3 mg’s (Novo Nordisk’s Victoza for obesity) phase 3 results, “Ahhh, it’s fantastic.”

Turning to the Middle East, speakers on both local and global topics underscored how daunting the diabetes and obesity epidemics are in this region. As background, the 6th Edition of the IDF Atlas indicates that the prevalence of diabetes in the Middle East and North Africa was 10.9% in 2013. Among the top ten countries for diabetes prevalence are Saudi Arabia (24%), Kuwait (23%), and Qatar (23%). Furthermore, it is our understanding that the Middle East is a young region (~50% of the population is under 18 years old), suggesting that as the population ages the prevalence of type 2 diabetes and its complications could by even “quite” terrifying. More specifically, Dr. Khalid Al-Rubeaan (King Saud University, Riyadh, Saudi Arabia) noted that about one-fourth of adults in the Gulf States have prediabetes, and the annual incidence of diabetes is 1%. The diabetes and obesity epidemics are also taking a financial toll: according to Dr. Al-Rubeaan, one-fifth of the GCC’s annual health budget is spent on diabetes and its complications. Additionally, Dr. Davit Sargsyan (Hamad Medical Corporation, Doha, Qatar) provided details on the performance of bariatric surgery in Qatar. In 2013, the center conduced 686 surgeries, which Dr. Sargsyan indicted compares against an average at North American and West European surgery centers of 200-300 cases a year.

See bellow for our top ten learnings from the meetings, as well as detailed reports on the most nuanced presentations we attended.

Top Ten Highlights

1.During a Novo Nordisk symposium, Dr. Buse stated his belief that Novo Nordisk’s Tresiba (insulin degludec) and Victoza (liraglutide) are “arguably the two most powerful glucose-lowering agents on Earth.” IDegLira, the fixed-ratio combination of these two drugs, is, in his view, the “most powerful agent we have even contemplated in type 2 diabetes”,— strikingly powerful words that he proceeded to support with IDegLira’s phase 3 data. Dr. Buse characterized the phase 3 trials of IDegLira DUAL-I and DUAL-II as the “two most exciting studies [he has] done” out of the roughly 200 research studies he has conducted over the last 30 years. Looking to the day IDegLira reaches the market, Dr. Buse suggested that physicians might initiate a type 2 diabetes patient on IDegLira when they feel it is particularly crucial for a therapy to “work” (i.e., not require subsequent escalation of injectable therapy or cause major tolerability issues, both of which are demoralizing for patients). The question remains whether IDegLira will be seen as an initial injectable or as a second-line injectable – Novo Nordisk continues to position it as an escalation step for people already on GLP-1 or basal insulin and needing extra help, although we can see how it would also make sense to simply start someone on IDegLira rather than sticking to the old treat-to-failure model. IDegLira has better efficacy and a better side effect profile (less nausea than GLP-1 agonists, less hypoglycemia than basal insulin) than either GLP-1 or basal insulin alone. For more details on Dr. Buse’s comments and DUAL-I and DUAL-II please see the appendix.

2.In Dr. Buse’s “Interrogate the Expert” session, he suggested that “the two ugliest trials in the history of diabetes” were EXAMINE and SAVOR-TIMI 53, the cardiovascular outcomes trials of Takeda’s alogliptin (Nesina) and AZ’s saxagliptin (Onglyza), respectively. Dr. Buse also hypothesized that ongoing CVOTs are “extremely unlikely to show benefit with CV outcomes.” His rationale was that EXAMINE and SAVOR were done for “the somewhat crass reason that the FDA required some evidence of CV safety,” and were expensive and required many participants. Furthermore, to speed along the trial, the companies opted to enroll quite ill patients (in the case of EXAMINE) or a very large number of patients (in the case of SAVOR; n=16,492) (EXAMINE and SAVOR participants were followed for a median of 2.1 years and 1.5 years, respectively). As a result, Dr. Buse thinks it is difficult to draw complex conclusions on the agents’ long-term efficacy and safety in relatively healthy patients. Dr. Buse was more optimistic about the potential for TECOS Merck’s CVOT of sitagliptin (Januvia) and LEADER Novo Nordisk’s CVOT of liraglutide (Victoza) to produce more nuanced results since they will be longer in duration (about five years of follow-up in each). In particular, Dr. Buse was hopeful these trials, as well as meta-analyses of multiple CVOTs, would teach researchers about unexpected adverse events and disprove (or prove) safety concerns raised in preclinical and epidemiological studies.

3.In a presentation updating attendees on SGLT-2 inhibitors (none have been launched in the Gulf yet), Dr. John Wilding (University of Liverpool, Liverpool, United Kingdom) suggested the class might be renal-protective. Dr. Wilding stated that he would not detail his reasoning; however, at CODHy 2012, Dr. Ralph DeFronzo (University of Texas Health Science Center, San Antonio, TX) explained that an SGLT-2 inhibitor could protect the kidney by reducing the hyper-filtration of glucose it typically conducts in type 2 diabetes. Additionally, he noted that in rats SGLT-2 inhibitors have been shown to reduce the intraglomerular pressure, and prevent kidney failure. Dr. DeFronzo also drew attention to end-stage renal failure being the only renal endpoint currently accepted for demonstrating renal protection in humans. Dr. DeFronzo did not believe that a company would perform a study of a SGLT-2 inhibitor long enough to look at this endpoint. Nonetheless, J&J recently initiated a renal outcomes study for its SGLT-2 inhibitor, Invokana (canagliflozin), called CREDENCE.

4.During a Medtronic sponsored workshop, Dr. Ghassan Naboulssi (Education Manager, Medtronic Diabetes, Middle East & North Africa, Lebanon) expressed great confidence in Medtronic’s artificial pancreas program. Dr. Naboulssi passionately told attendees, “the Veo will be the heart of the artificial pancreas; I can confirm this. That is why we call the Veo the semi-artificial pancreas.” When asked when the closed-loop system would be available Dr. Naboulssi responded “soon enough.” He acknowledged that researchers have been guiding for the AP being available “in the next five years” for more than a decade. Yet, he pressed that recently the timeline has become “much, much earlier than five years. At least I can promise to you now, but I cannot deliver anything.” He went on to note “the closed-loop system is ready.” For background, the first-in-human data for Medtronic’s orthogonally redundant CGM (using glucose oxidase and optical sensing) was presented at ATTD 2014, and a study of the system is ongoing. Medtronic also has an overnight closed-loop system in development, which according to the company’s 2012 Analyst Day Timeline, is to be launched in May 2016 or later.

5.Throughout EiD, speakers emphasized their concern with the Gulf region’s strikingly high – and rapidly rising – diabetes prevalence. Dr. Khalid Al-Rubeaan (King Saud University, Riyadh, Saudi Arabia) presented more details on the “Diabetes Storm Hitting the GCC Countries:” about one-fourth of adults in the Gulf States have prediabetes, and the annual incidence of diabetes is 1% (i.e., each year an additional percentage point of the population develops diabetes). Among people with diabetes, about one-third have retinopathy and 10% of these are blind. Furthermore, one-fourth of people with diabetes in the GCC have heart disease at some point during their life, and 10% of people with diabetes in the region die each year. Diabetes is also coming at a great financial cost to the region. According to Dr. Al-Rubeaan, one-fifth of the GCC’s annual health budget is spent on diabetes and its complications. In Saudi Arabia, this translates to ~$10 billion being spent each year on type 2 diabetes and an additional $1.8 billion being spent on type 1 diabetes. We note that experts on diabetes care in the Middle East frequently cite lack of reliable data as an obstacle to care. Very few diabetes registries exist so the important epidemiological studies that are conducted often have to make more estimates than would be ideal – and this, in a very data-driven region.

6.Dr. Davit Sargsyan (Hamad Medical Corporation, Doha, Qatar) also provided details on the performance of bariatric surgery in Qatar. Dr. Sargsyan painted a picture of the current obesity epidemic in Qatar: a 2013 survey conducted by the Supreme Council of Health in Qatar found that 30% of people in Qatar are overweight and 41% are obese. Since the Hamad Medical Corporation (the main provider of healthcare in Qatar) established a bariatric surgery center in February 2011, the center’s six surgeons have conducted 1,697 bariatric surgeries. The number of surgeries performed at the center has increased each year, and in 2013, the center performed 686 surgeries. For comparison, Dr. Sargsyan remarked that the average North American or West European surgery center conducts 200-300 cases a year. Dr. Sargsyan indicated that the main barrier to more bariatric surgeries being preformed in Qatar is the shortage of trained surgeons ­– his center currently has a wait-list of almost 4,000 people.  

7.Looking at liraglutide 3 mg’s (Novo Nordisk’s Victoza for obesity) phase 3 weight loss data, Dr. Jens Holst (University of Copenhagen, Denmark) exclaimed, “Ahhhh, it’s fantastic.” Additionally, Dr. Holst highlighted that in SCALE-Obesity and Prediabetes, 69% of the prediabetes subgroup (61% of all study participants had prediabetes) treated with liraglutide no longer showed signs of prediabetes at week 56, compared to 33% of the placebo-treated group. Among people without prediabetes at randomization, 7% of those on liraglutide and 21% of those on placebo developed prediabetes. Therefore, Dr. Holst expressed optimism that liraglutide 3 mg might be able to prevent type 2 diabetes. On the safety side, Dr. Holst was confident that the agent will not have any CV issues since it acts on a person’s appetite rather than his/her metabolic rate. He also noted that liraglutide 3 mg is “surprisingly well behaved”  (presumably meaning on the side-effect front). In SCALE-Obesity and Prediabetes, the completion rate was 72% for liraglutide and 64% for placebo. Withdrawals due to adverse events were below 10% in both arms (specific withdrawal rates were not provided). For background, Novo Nordisk announced in December 2013 that it had filed liraglutide 3 mg in the US and EU. Novo Nordisk noted during its December Capital Markets Day that clinical trials of liraglutide 3 mg have shown imbalances in pancreatitis and gall bladder disorders. Novo Nordisk expects in-depth discussion on these concerns at a likely Advisory Committee meeting in 3Q14.

8.Dr. Stephen Leeder (The University of Sydney, Australia) cited a US study in which 19% of elderly respondents indicated that they had to cut back on their diabetes medication in the prior year due to cost (Piette et al., Diabetes Care 2004). We find this result to be distressing because the costs saved by reducing medications may have ultimately compounded into more costly complications and hospitalizations. Furthermore, this survey was conducted before reducing healthcare expenditures came under such heavy focus. This finding suggests that some people were already struggling with the out of pocket expenses of diabetes, and we fear an even greater percentage did not have to cut back on medications due to cost but had little financial buffer for their medical expenses to increase. We hope that as policy makers and healthcare administrators work to eliminate the waste that exists in the healthcare system that they will be mindful of not creating financial disincentives for people to take preventative medications.

9.Dr. Stephen Colagiuri (University of Sydney, Australia) was interrogated on the “unfolding nightmare” of diabetes and obesity. Dr. Colagiuri, who is currently Chair of the IDF Task Force on Clinical Guidelines, indicated that the IDF’s model for the current and future prevalence of diabetes is probably “quite conservative.” As a reminder, the 6th Edition of the IDF’s Diabetes Atlas states that 382 million people had diabetes in 2013 and projected that 592 million people will have diabetes in 2035. Dr. Colagiuri noted that a Markov model (which unlike the IDF model considers trends in smoking and urbanization) of Saudi Arabia’s diabetes prevalence than the IDF’s has been published, which suggests IDF’s estimate is low for the nation (Al-Quawaidhi et al., Diabetes Res Clin Pract 2014). The Markov model placed Saudi Arabia’s diabetes prevalence at 29% in 2011, as compared to the IDF’s estimate of 17%. It also projects Saudi Arabia’s prevalence to be 44% in 2030 in contrast to IDF’s estimate of 21%.

10.Dr. George Bray (Pennington Biomedical Research Center, Baton Rouge, LA), a Look AHEAD investigator, provided additional insight on what went wrong – and right – in the trial. First, according to Dr. Bray, when the trial was being originally developed the researchers thought that they might be able to use weight loss agents like sibutramine to ensure people lost more weight. Second, Dr. Bray hypothesized that the reason the control group began to lose weight toward the end of the trial’s duration (shrinking the gap between the control and intervention arms) is because elderly people naturally lose weight, and the enrollees were too old at baseline (59 years). Finally, Dr. Bray repeatedly suggested that microvascular outcomes should have been the primary endpoint. Other attendees joined Dr. Bray in pressing that the Look AHEAD trial should not be considered a failure, since it proves the dramatic impact lifestyle intervention can have on many aspects of health, even if one of those benefits is not macrovascular outcomes.  

Appendix: Detailed Discussion and Commentary

Corporate Symposium: Advancements in Diabetes Treatment and Improvement in Patient Outcomes

Advancement in Diabetes Treatment and Improvement in Patient Outcomes

John Buse, MD, PhD (University of North Carolina, Chapel Hill, NC)

Dr. John Buse stated his belief that Novo Nordisk’s Tresiba (insulin degludec) and Victoza (liraglutide) are “arguably the two most powerful glucose-lowering agents on Earth.” Together, in his view, they form the “most powerful agent [the fixed-ratio combination IDegLira] we have even contemplated in type 2 diabetes”— strikingly powerful words that he proceeded to support with the IDegLira’s phase 3 data. Dr. Buse called the phase 3 trials of the agent DUAL-I and DUAL-II “the two most exciting studies I have done” out of the ~200 research he has conducted in the last 30 years. Looking to the day IDegLira reaches the market, Dr. Buse suggested that physicians might initiate a type 2 diabetes patient on IDegLira when they feel it is particularly crucial for a therapy to “work” (i.e., not require subsequent escalation of injectable therapy or cause major tolerability issues, both of which are demoralizing for patients). The question remains whether IDegLira will be seen as an initial injectable or as a second-line injectable – Novo Nordisk continues to position it as an escalation step for people already on GLP-1 or basal insulin and needing extra help, although we can see how it would also make sense to simply start someone on IDegLira rather than sticking to the old treat-to-failure model. IDegLira has better efficacy and a better side effect profile (less nausea than GLP-1 agonists, less hypoglycemia than basal insulin) than either GLP-1 or basal insulin alone.

  • Dr. Buse believes that IDegLira is a combination of “arguably the two most powerful glucose-lowering agents on Earth.” Together, in his view, the two form the “most powerful agent we have even contemplated in type 2 diabetes”— strikingly powerful words that he proceeded to support with the IDegLira’s phase 3 data. Regarding DUAL-I and DUAL-II, two major phase 3 studies for IDegLira, Dr. Buse exclaimed, “It’s time to wake up! I have conducted about 200 research studies over the last 30 years, and am going to talk about the two most exciting studies I have done.” See our ADA 2013 Incretin Report for Dr. Buse’s presentation of the full results from DUAL-I, which found a remarkable 1.9% mean A1c reduction (baseline of 8.3%) with IDegLira, helping over 80% of patients on IDegLira achieve a goal of 7.0% or below. IDegLira was also better than liraglutide or insulin degludec monotherapy with regards to hypoglycemia (one third less than with degludec despite a 0.5% lower A1C) and weight (slight weight loss, instead of weight gain with Tresiba). DUAL-II (full results presented at IDF) further demonstrated the benefits of IDegLira versus insulin degludec monotherapy for efficacy (A1c reduction of 1.9% vs 0.9% from a baseline of 8.7%) and weight (~6 lbs. lost versus weight neutrality).
  • Dr. Buse told the story of his first time using a GLP-1 agonist with a patient back in 1999, more than five years before exenatide (Byetta) became available in the US. At the time, Dr. Buse was conducting a five-day crossover trial comparing placebo and exenatide in six patients already on NPH. He remembered that the first patient he worked with had a blood glucose level of about 100 mg/dl in the morning. Dr. Buse gave the patient a shot of exenatide before breakfast. When he then tested the patient’s blood glucose level, he assumed the YSI Analyzer was broken, as it still read 100 mg/dl. “I had never seen numbers like that before,” Dr. Buse remarked. “The hair on the back of my neck stood up. I was so enervated by it.”
  • Looking to the day IDegLira reaches the market, Dr. Buse suggested that physicians might initiate a type 2 diabetes patient on IDegLira when they feel it is particularly crucial for a therapy to “work” (i.e., not require subsequent escalation of injectable therapy or cause major tolerability issues, both of which are demoralizing for patients). This level of almost guaranteed success has been elusive thus far, but IDegLira’s attractive efficacy/side effect profile (or lack of side effects) makes it quite unique. The question remains whether IDegLira will be seen as an initial injectable or as a second-line injectable. While Novo Nordisk has positioned it as an escalation step for those already on GLP-1 agonists or basal insulin, starting IDegLira when injectable therapy is needed seems to make sense since it does not add any extra injections, has a more attractive side effect profile, and has greater efficacy.

Interrogating the Expert

Diabetes Research in the 21st Century: The Good, the Bad, and the Ugly

John Buse, MD, PhD (University of North Carolina, Chapel Hill, NC)

Dr. John Buse feels that “the two ugliest trials in the history of diabetes” were EXAMINE and SAVOR-TIMI 53, the cardiovascular outcomes trials of Takeda’s alogliptin (Nesina) and AZ’s saxagliptin (Onglyza), respectively. His rationale was that EXAMINE and SAVOR were done for “the somewhat crass reason that the FDA required some evidence of CV safety,” and were expensive and required many participants. Furthermore, the companies opted to enroll quite ill patients (in the case of EXAMINE) or a large number of patients (in the case of SAVOR; n=16,492) in order to keep the study’s duration relatively short (EXAMINE and SAVOR participants were followed for a median of 2.1 years and 1.5 years, respectively). As a result, Dr. Buse thinks it is difficult to draw complex conclusions on the agents’ long-term efficacy and safety in relatively healthy patients. Dr. Buse seemed more optimistic about the potential for more nuanced results to come from TECOS Merck’s CVOT of sitagliptin (Januvia) and LEADER Novo Nordisk’s CVOT of liraglutide (Victoza), because these studies will be longer in duration (five years each). In particular, Dr. Buse was hopeful these trials, as well as meta-analyses of multiple CVOTs, will teach researchers about unexpected adverse events and disprove safety concerns raised in preclinical and epidemiological studies.

  • Dr. Buse hypothesized that the ongoing CVOTs are “extremely unlikely to show benefit with CV outcomes.” As evidence he cited ORIGIN’s non-superiority finding for insulin glargine (Sanofi’s Lantus), as well as the trials’ tendency to enroll people with established CVD and the tendency for short trial durations. Dr. Buse continued, however, to say, “Arguably, the [CVOTs’] point is to demonstrate no harm, which is a pretty low bar for management techniques.” The study population most suited for non-inferiority studies is also quite different from the population that one would study to show superiority – the latter would be much younger, earlier in the disease progression.
  • Dr. Buse concluded his presentation by voicing his agreement with the NIH’s letter in Nature on enhancing the reproducibility of clinical trials. In the letter, NIH Direct Dr. Francis Collins cites critical issues in 1) major trial design flaws and statistical analysis issues, 2) PI hyperbole in reporting the reports (i.e., trying to convey negative trial results as positive), 3) publication bias against negative studies or those that do not stir controversy (Dr. Buse noted how small trials suggesting incretin mimetics cause pancreatic events garnered more attention than large studies disproving this hypothesis), 4) reliance on often misleading preclinical models, 5) misrepresentation of epidemiological findings (these study’s should be hypothesis generating for further research, however, conclusions are often derived from them), and 6) professional evaluation standards.   

 

GGSD Symposium

Diabetes Storm Hitting the GCC Countries: Health and Economic Impact

Khalid Al-Rubeann, MD (King Saud University, Riyadh, Saudi Arabia)

Dr. Khalid Al-Rubeaan presented some startling details on the “Diabetes Storm Hitting the GCC Countries:” about one-fourth of adults in the Gulf states have prediabetes, and the annual incidence of diabetes is 1% (i.e., each year an additional percentage point of the population develops diabetes). Among people with diabetes, about one-third have retinopathy and 10% of these are blind. Furthermore, one-fourth of people with diabetes in the GCC have heart disease at some point during their life, and 10% of people with diabetes die each year. Dr. Al-Rubeaan stated that in a Saudi Arabian community survey of people with diabetes 65% had “poor control” as measured by a random blood glucose value (definition of “poor control” not provided), 25% had “moderate control”, and 10% had “good control.” In a hospital survey of inpatients with diabetes 75% had “poor control” as defined by A1c, 15% “moderate control”, and 10% “good control.” Diabetes is also coming at a great financial cost to the region. According to Dr. Al-Rubeaan, one-fifth of the GCC’s annual health budget is spent on diabetes and its complications. In Saudi Arabia, this translates to ~$10 billion being spent each year on type 2 diabetes and an additional $1.8 billion being spent on type 1 diabetes. We note experts on diabetes care in the Middle East frequently cite lack of reliable data as an obstacle to care.. Very few diabetes registries exist so the important epidemiological studies that are conducted often have to make more estimates than would be ideal.  

  • According to Dr. Al-Rubeaan, Saudi Arabia (which according to the IDF has 3.6 million people with diabetes) spends about $10 billion a year on type 2 diabetes and $1.8 billion a year on type 1 diabetes. The breakdown of money spent on type 2 diabetes included $6.6 billion on hospital care, $1.4 billion on drugs and supplies, $1.1 billion on foot ulcers, $840 million on dental care, $400 million on dialysis and kidney transplant, $142 million on impotence, and $83 million was spent on cataract surgery. In type 1 diabetes, $1.1 billion was spent on hospital care, $333 million was on drugs and supplies, and $150 million was on foot ulcers. For comparison, the United States has ~24.5 million people with diabetes and the ADA estimated that the direct medical cost of the disease in the US was about $176 billion in 2012. It is, of course, challenging to compare across cost-burden models (as each has different methodology), however, the IDF estimates that the US in 2013 spent a mean of $9,800 on each person with diabetes and that Saudi Arabia spends $943.   
  • Dr. Al-Rubeaan estimated that the indirect cost of diabetes in Saudi Arabia at almost $24 billion a year – about $6,500 per person with diabetes (using the IDF’s estimate of people with diabetes living in Saudi Arabia). For comparison, the ADA estimated the indirect cost of diabetes in the US at $69 billion in 2012, or $2,820 per person with diabetes (using the IDF’s estimate of people living with the disease). Dr. Al-Rubeaan did not highlight nor discuss this difference. His estimate of the disease’s indirect cost includes resultant salary deductions, sick leave, early retirement, disabilities, infections, and mortality.
  • Treatment demand from today to 2025 in the Gulf Cooperation Council (GCC; Bahrain, Kuwait, Oman, Qatar, Saudi Arabia, and the UAE) is expected to grow most dramatically for CVD and diabetes. Demand for CVD treatment is expected to rise 419% and demand for diabetes treatment 323%. Furthermore, other areas of high demand growth are related to diabetes. For example, the third greatest increase in demand (by 293%) is expected in “sense organ diseases,” which Dr. Al-Rubeaan noted largely consists of retinopathy. This is especially distressing given that landmark studies (UKPDS and other) show microvascular complications can be prevented with better glycemic control.
  • According to a report from the 74th Meeting of the Health Minister’s Council for Cooperation Council States, Bahrain’s government allocated the greatest percentage of its resources to healthcare at about 12%. This translated to healthcare spending by the government of $864 per capita and $1.1 billion total. The next highest was the United Arab Emirates at ~8% ($1,450 per capita and $11 billion total), then the Kingdom of Saudi Arabia at ~7% ($680 per capita and $19 billion total), Oman at ~6.5% ($574 per capita and $1.6 billion total), Qatar at ~6% ($1,489 per capita and $2.6 billion total), and lastly Kuwait at ~4% ($1,233 per capita and $3.3 billion total).  These countries financed about ~70% of all healthcare spending (with ~20% being self-funded and ~10% being other [likely private insurance companies]) – the Saudi Arabian government funded the smallest portion at ~60% (another 20% household funded and  10% other), and Kuwait’s government paid the largest portion at ~80% (~18% self-funded and 2% other).
  • Dr. Al-Rubeaan underscored the strain that is going to be placed on Gulf healthcare systems by rapidly rising demand for hospital beds. From today (at 65,250 beds) to 2025 the GCC overall the demand for hospital beds is expected to grow 140%. The highest jump in demand is expected to occur in the UAE (up 160%; followed closely by Saudi Arabia at 145%), and the smallest increase in Bahrain (80%).
  • Looking at the reasons for the GCC’s rapidly escalating diabetes and obesity epidemics, Dr. Al-Rubeaan highlighted the very high (and increasing) per capita food consumption in the region. The World Bank estimates that the average person in the GCC from 1997-1999 consumed ~3,400 calories a day, as compared to ~2,900 in industrialized countries, and ~2,700 in developing countries. In 2030, the average person in a GCC country is expected to consume ~3,600 calories a day (Dr. Al-Rubeann hypothesized calorie consumption might be actually increasing more dramatically and that some areas might have already passed 4,000 calories a day). This compares against ~3,200 in industrialized countries and ~3,000 in developing countries.

Role of Bariatric Surgery in Diabetes

Davit Sargsyan, MD (Hamad Medical Corporation, Doha, Qatar)

Dr. Davit Sargsyan provided details on the performance of bariatric surgery in Qatar. Dr. Sargsyan painted a picture of the current obesity epidemic in Qatar: a 2013 survey conducted by the Supreme Council of Health in Qatar found that 30% of people in Qatar are overweight and 41% are obese. Dr. Sargsyan indicated that “some experts” predict that 73% of Qatari women and 69% of Qatari men will be obese by 2015. Since the Hamad Medical Corporation (the main provider of healthcare in Qatar) established a bariatric surgery center in February 2011, the center’s six surgeons have conducted 1,697 bariatric surgeries. In 2013, the center conducted 686 surgeries. For comparison, Dr. Sargsyan remarked that the average North American or West European surgery center conducts 200-300 cases a year. Dr. Sargsyan indicated that the main barrier to more bariatric surgeries being preformed in Qatar is the shortage of trained surgeons ­– his center currently has a wait-list of almost 4,000 people.

  • According to a survey conducted in 2007-2008 by Hamad, 53% of Qatari women over 20 years old and 47% of men had diabetes. For comparison, the Third Edition of the IDF’s Diabetes Atlas estimated that the national prevalence of diabetes for people 20-79 years old in 2007 was 12.7% (it projected that the national prevalence would be 17.1% in 2025; however, the Sixth Edition of the Atlas stated that the prevalence of diabetes had already reached passed 22% in 2013). A challenge in comparing these estimates is that Qatari nationals currently comprise ~30% of the country’s population. However, our understanding is that diabetes prevalence tends to be similar between expats and natives, so we are uncertain where the biggest discrepancies lie.
  • Of the 1,697 bariatric surgeries Dr. Sargsyan’s center has performed, the most common procedure has been the gastric sleeve (75%). The second most common procedure has been roux-en-Y gastric bypass (9%). Interestingly, this stands in contrast to western countries where Roux-en-Y gastric bypass is still largely considered the “gold standard,” and the sleeve’s popularity recently began to rise (though it is rising quite quickly).
  • The majority of the people who have undergone bariatric surgery at the Hamad Medical Corporation were women (65%) and Qatari (72%). The most common age-groups among patients were 30-39 years old (34%) and 20-29 years (26%); 6% of surgeries were performed in children 12-19 years old, and 1% was conducted in people older than 60 years. The most common BMI group was 40-49 kg/m2 (45%) and 2% of cases were in people with a BMI <30 kg/m2.
  • Dr. Sargsyan called bariatric surgery the “best treatment available for diabetes.” Fifty-nine percent of Hamad’s bariatric surgery patients had an obesity-related comorbidity, and 24% had diabetes at the time of operation. Dr. Sargsyan indicated that 61% of people with diabetes undergoing bariatric surgery at Hamad stopped their medications (length of follow up not provided), 34% reduced their medications, 5% stayed on the same medication doses, and 0% intensified their treatment.
  • When considering the question of bariatric surgery’s cost-effectiveness, Dr. Sargsyan noted that this is not a “top issue” in Qatar. This is because the Qatar government completely covers a Qatari national’s undergoing bariatric surgery.  Dr. Sargsyan noted that the cost-effectiveness of the approach could come under heavier scrutiny in the country if private payers begin to play a larger role in the nation’s healthcare. For context, other Gulf states, including the United Arab Emirates, have begun to see a gradual privatization of their healthcare systems.  Still, Dr. Sargsyan expressed confidence that bariatric surgery is cost effective due to its beneficial impact on many obesity-related diseases.

 

Obesity

Look AHEAD

George Bray (Pennington Biomedical Research Center, Baton Rouge, LA)

Dr. George Bray, a Look AHEAD investigator, provided additional insight on “what went wrong” in the trial. Dr. Bray hypothesized that the three main mistakes the trialists made were 1) not achieving great enough weight loss; 2) enrolling too old of a population; and 3) selecting the wrong primary endpoint. First, according to Dr. Bray, when the trial was being originally developed the researchers thought that they might be able to use weight loss agents like sibutramine to ensure people lost more weight. Second, Dr. Bray hypothesized that the reason the control group began to lose weight toward the end of the trial’s duration (shrinking the gap between the control and intervention arms) is because elderly people naturally lose weight, and the enrollees were too old at baseline (59 years). Finally, Dr. Bray repeatedly suggested that microvascular outcomes should have been the primary endpoint. Other attendees joined Dr. Bray in pressing that the Look AHEAD trial should not be considered a failure, since it proves the dramatic impact lifestyle intervention can have on many aspects of health, even if one of those benefits is macrovascular outcomes. 

  • Dr. Bray suggested that intensive lifestyle intervention’s maximum weight loss (at year one) of 8.6% might have needed to be >10% in order to have the impact on macrovascular disease the investigators were seeking. Indeed, according to Dr. Bray, when the trial was being originally developed the researchers thought that they might be able to use weight loss agents like sibutramine to ensure people lost more weight.
  • Dr. Bray could not review the microvascular results, as a paper on the topic is about to be published. However, at ADA, Dr. William Knowler (NIDDK, Phoenix, AZ) announced that the intervention reduced the incidence of very-high-risk CKD by 31% (HR:0.69; 95% CI: 0.55-0.87) and provided favorable effects on several renal endpoints (e.g., progression to eGFR <45 ml/min/1.73m2, albumin:creatinine ratio ≥300 mg/g, or renal replacement therapy).
  • Dr. Bray hypothesized that the reason the control group began to lose weight toward the end of the trial’s duration is because elderly people naturally lose weight, and the enrollees were too old at baseline (59 years). Since the average person was in the trial for 9.6 years, the average enrollee was almost 70 years old when the study was discontinued. Thus, the participants might have entered a phase of their life when they naturally lost weight, blurring the intervention’s impact.

 

--by Hannah Deming and Kelly Close