Diabetes Treatments

Products” may have interesting implications for diabetes. diabetes panel with Drs. Charles Clark (Indiana University) and George King (Joslin Clinic) was …

Diabetes Close Up, V3, 6 March 17, 2004 The short version 1 2 Happy St Patricks Day Two FDA reports see Appendix A, page 2-4 a Part 1: Yesterdays report Innovation Stagnation: Challenge and Opportunity on the Critical Path to New Medical Products may have interesting implications for diabetes b Part 2: Last weeks report on obesity Calories Count less than compelling Cowen Conference: SG Cowen had a terrific investment conference in Boston last week; see highlights in Appendix B, page 5-8, on Medtronic, Lilly, Novartis, and others In particular, the diabetes panel with Drs Charles Clark Indiana University and George King Joslin Clinic was outstanding In the standing-room-only big ballroom, the good doctors mused on everything from inhaled insulin decidedly negative to the growth of type 2 diabetes patients are walking time bombs to dual PPARS very exciting - and were waiting for a trial to show these are antiatherogenic to DPP-IVs probably not a more effective and safe method of regulating GLP-1 than administering a GLP-1 analog to Lantus impact on insulin pump prescription No impact they said, flatly to timing of continuous sensor technology 5-10 years for a serious impact then
again, what does serious mean? Taking even 10 share of the most profitable episodic monitoring customers could enable blockbuster sales results for the category Obesity roundup: All this obesity news is frankly exhausting, no? Information is good, but now, now, we have enough information Lets focus on action, pun intended the energy equation is theoretically simple; so lets look at how to change behavior See Appendix C, page 9-11 for a review of obesity news to date in 2004, along with an in-depth look at the USs official objection to WHOs plan to halt obesity, which we see as an, um, suboptimal approach to the issue Media Roundup: Numerous peer-reviewed pieces of note, and a cool documentary - see Appendix D a Diabetes Care, March, 2004 two key pieces of note: 1 Improved Glucose Excursions Using an Implantable Real-Time Continuous Glucose Sensor in Adults With Type 1 Diabetes: DexComs first published results are the March Diabetes Care; and 2 Dr David Klonoffs Editorial, The Need for Separate Performance Goals for Glucose Sensors in the Hypoglycemic, Normoglycemic, and Hyperglycemic Ranges b Super Size Me In this novel documentary, the director seeks to find out what happens
when McDonalds is eaten three times a day for 30 days straight ADA preview/other conferences: This time of year is so exciting, as the schedules start to come out for all the major conferences Were at Diabetes 2004 UK wwwdiabetesorkuk/apc starting today, in Birmingham, England; then weve got the UCSF diabetes update wwwmedicineucsfedu/cme and AACE wwwaacecom next month, ADA Southeastern in May, ADA in June both wwwdiabetesorg, AADE wwwaadenetorg in August, and EASD wwweasdorg in September Preview highlights, coming soon Observations: a Diabetes 2004 This is now available; see our website wwwcloseconcernscom Please let us know if youd like to receive the table of contents b St Patricks Day Hope you have had a wonderful day; even though I changed my name from Shaughnessy to Close three years back, I still consider this one of the most important holidays of the year Im thinking today fondly of my grandfather, father, brother, and cousin all named Patrick Great name, isnt it Patrick Shaughnessy

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The l o n ger version Appendix A: The FDAs Latest Part 1: The FDA on Innovation
Stagnation The FDA put out a new report yesterday, Innovation Stagnation: Challenge and Opportunity on the Critical Path to New Medical Products on ways to speed drugs to market Im not sure how much is rhetoric, but the main finding appears to be that the medical product development process is no longer able to keep up with basic science innovation Whats that old saying about acknowledgement being the first step to change? Hopefully weve moved out of the state of denial A concerted effort is obviously needed to apply the new biomedical science to medical product development, which would enable faster, more successful drug development A few points of interest directly or indirectly related to diabetes and/or obesity, clearly the major public health issues of the moment: 1 The FDA notes a basic disconnect between discovery and product development FDA is now planning an initiative that will identify and prioritize 1 the most pressing development problems and 2 the areas that provide the biggest opportunities for rapid improvement and public health benefits Theoretically, this bodes well for diabetes, so Id view it as a positive; although its unclear how quickly the agency will act in
practice If theres any doubt that were at a troubling point, see Figures 1 and 2 in the report, which can be found at wwwfdagov/oc/initiatives/criticalpath/whitepaperpdf - Figure 1 shows how pharma and NIH spending has increased substantially over the last decade, while major drug and BLA submissions have plummeted Indeed, the contrast is striking, and while we all know these numbers, actually looking at the trend over the past decade is sobering The slowdown in medical device submissions is also highlighted An analysis by Windhover and Bain show that from 1995-2000, the estimated cost of taking a drug from discovery phase to launch was 11 billion; from 2000-2002, this estimate rose to an alarming 17 billion While the latter figure may be skewed due to a small number of approved drugs, it is still quite disturbing Unsurprisingly, the majority of the increased costs over that short time period stem from Phase III and launch expenses The report implies that many more drugs should be killed earlier in the process, and that the FDA alone has valuable information that could make that happen FDA reviewers, they say, are in a unique position to help identify common themes and systematic
weaknesses in similar products and can draw key lessons from what they find Id love to see this report - as yet, it too appears to be theoretical Areas with guidance documents are said to be nearly twice as likely to be approved after the initial review process and are approved in a third less time Stay tuned a guidance document is in the works for weight loss drugs see Appendix A, part 2 The agency says there is an urgent need for improvement in efficiency and effectiveness of the clinical trial process, including improved trial design, endpoints, and analyses They claim they will address this in roadmap efforts, which I would take as a cautiously positive sign, depending on how fast they can work The report quotes an article in which an official from Pfizer notes that liver toxicity alone has cost them over 2 billion in the last decade This of course is an oblique reference to Rezulin While the FDA seems to suggest that this is solely due to an unforeseen safety issue, I would argue that it is more complex; that labels werent followed, patients were not always getting tested when asked to, and doctors werent able to spend enough time with patients discussing tests1 The report
offers examples of tools that are urgently needed, namely methods to further enhance the safety of transplanted human tissues others listed are better predictors of human immune responses to foreign antigens and new techniques for assessing drug liver toxicity I would view this

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I had a letter published in the New York Times business section on Sunday, March 6, 2004 responding to a February 29, 2004 piece entitled Is Biotechnology Losing Its Nerve? Unfortunately, the NYT doesnt include letters on its website but let us know if youd like a copy and we will send it to you

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as a potential positive on the islet cell front, though cell source supply with immunosuppression in second place still represents a major challenge The report also stresses that more focus is needed on industrialization challenges - many product failures during development are ultimately attributable to problems relating to the transition from lab prototype to industrial product, the report notes The FDA highlights progress in blood glucose monitoring as a success for the countrys
patients with diabetes, emphasizing that numerous new devices are being developed for blood glucose monitoring I would take as a successful sign, as one of these - TheraSenses Navigator is at the agency now and Medtronics Guardian 2 should be submitted shortly I cant imagine if prospects were poor for continuous monitoring that they would highlight, even in sideways fashion, the new technology In terms of their success, the report reference the fact that separate accuracy and precision goals were defined for extreme ranges to keep pace with changing clinical demands for tighter glucose measurement True, although the ranges probably arent extreme enough, per Dr David Klonoffs impressive editorial in this months Diabetes Care see Appendix D, Media Roundup A quick follow up - I was surprised and disappointed to see the report reference the countrys 16 million diabetics - this statistic is flipping two years outdated The current estimate exceeds 18 million I sent them an e-mail referring them to the CDC website - while the agency frequently stresses how committed it is to diabetes, this wont heighten confidence Also of potential importance to the blood glucose monitoring front, the
report says that additional characterization procedures and standards for implanted drug-device combinations are urgently needed This will be interesting to watch as work progresses on the artificial pancreas front Ultimately, I would be cautious about interpreting this report as a real positive; for now, I would stand aside and watch how things play out The report does appear to heighten the urgency with drug development and hopefully this will play out to our collective benefit: If we do not work together to find fundamentally faster, more predictable, and less costly ways to turn good biomedical ideas into safe and effective treatments, the hoped-for benefits of the biomedical century may not come to pass or may not be affordable Exactly Lets push for moving rhetoric into real action

Part Two: The FDA on Obesity So the FDA published a long-awaited obesity report last week http://wwwfdagov/oc/initiatives/obesity/ Im not going to spend much time on this report because in my view its not worth it Suffice to say, I did not find this 39-page piece particularly compelling at first read the references are the best part Why? There is just not a lot of conviction in the report about
what should happen; mostly, it encourages food companies and restaurants to do things like make new labels with bigger font for calories sort of strange, its written as if its a new idea, give nutrition information on menus I know its expensive for restaurants to do this and I sympathize, but how about a plan, even over the next decade, to enforce this rather than just suggest it? and encourages consumers to eat less and exercise more ah yes, the old energy equation We know it backwards and forwards At first glance, to say the least, I would not imagine that obesity is going to decline in the near or long term as a result of the report While I realize that we need to tread carefully here admittedly, a lot of ideas I like are costly I think its shameful that it took them this long to come up with most of these ideas The one great thing is some new advertising see http://wwwadcouncilorg/campaigns/healthy_lifestyles/ These are excellent ads apparently the government is spending about 10 million on them wont come close to the billions spent by fast food and soft drinks, but its a start Some other ideas the report doesnt explore: 1 How about looking further into a fat tax? Possibly
unpopular and maybe even wrong, but I bet it would have some serious impact look what taxes did for tobacco use 2 How about if insurance gave people a break for good cholesterol scores, achieving and maintaining weight loss, achieving and maintaining better A1Cs, etc? Yes, costly to track, but people do anything for a deal 3 How about if the government subsidized gym expenses? 4 How about mandating over time no sugar-sweetened drinks in schools? Put water bottles in those machines

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How about mandating, again, over time, more physical activity both at home and work, and heres the rub, think creatively about how to reward people I attended recently an AHA symposium on Prevention of Overweight and Its Consequences Beginning in Youth where USC exercise expert Dr Russell Pate pointed out that while 13 of American schoolchildren get to school in a nonmechanical way ie, walking or biking in Australia, that figure climbs to 43, and in Denmark and Germany, to 60 and 85, respectively The worst thing? Pate thinks 13 is an overestimate How about even simple things, like signs reminding people
to take the stairs?

The main item of note with possible industry implications was a recommendation to revise and reissue the FDAs 1996 draft guidance for the clinical evaluation of weight-control drugs This action item reflects the fact that some obese and extremely obese individuals are likely to need medical intervention to reduce weight and mitigate associated diseases and other adverse health effects FDA would issue this revised guidance for public comment It may take eons to emerge, but this is one to watch for — by Kelly Close

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Appendix B: SG Cowen Conference Review Fantastic I found the SG Cowen conference an extremely impressive investment conference Many of you know that they bring in loads of experts and do series of panels on various therapeutic areas The panel on diabetes was excellent, as the doctors spoke very candidly Although its true that Drs Charles Clark and George King represent two viewpoints only, two very highly regarded viewpoints at that A summary of my interpretation of their most interesting points follows The companies may have been a bit less transparent than
the doctors but here, too, an interpretation of nuggets of interest is noted below SG Cowen analysts started off the session by reeling off some statistics on the diabetes front: 1 Drugs related to diabetes achieved 13 billion in worldwide sales last year and should reach 20 billion by 2008 10 compound growth Compound 2003 sales 2008E sales a Insulin 47 billion 93 billion b Glitazones 36 billion 63 billion c Sulfonylureas 10 billion 12 billion d Other 37 billion 32 billion Revenue is concentrated; sales by Novo, Takeda, Eli Lilly, and Glaxo represent 68 of the total Diabetes is most key to Novo and Takeda in terms of overall product portfolios Trends: a Insulin will become a more primary treatment insulin sales should double over next five years, capturing nearly 50 of the diabetes drug market for b Glitazones have been and will continue to be big, as they delay the onset of insulin requirements, which is still a major goal for many type 2 patients c Dual PPARS will be key to watch, especially for lipid management d Inhaled insulin could further expand the insulin market, but long-term safety is still a stock overhang e Emerging GLP-1 compounds have terrific physiological
profile and broad use between these agents and insulin is expected Survey highlights: As part of the conference, panelists and audiences participated in real-time voting on a range of questions This is always excellent fun At the diabetes panel, a discussion with Drs Clark and King ensued King, by the way, is one of the patent holders in an exciting area, the PKC beta inhibitor2 a Dual PPARs: i The most promising dual PPAR is being developed either by AstraZeneca or Eli Lilly, according to the good doctors 24 of the audience chose BMS ii New PPARs in the clinic are promising in light of potential benefits related to lipid modulation, glucose reduction, body weight reduction, and relative side effect profile iii Both of the doctors believed that newer glitazones offered key advantages over Avandia and Actos iv Innovation in this area is very exciting, said Dr King Most PPARS are dual agnostics, meaning they have lipid and other advantages, and they may be antiatherogenic The animal data is strong, but we are still waiting for larger trial data v On current TZD agonists: 16 of people on insulin have fluid accumulation that could be clinically significant, said Dr King vi Dr Clark
expressed enthusiasm about the drugs Type 2 patients are a walking time bomb for cardiovascular disease, he said, noting that they take two to three pills each for blood glucose, hypertension, lipids, etc If we can have drugs do some or all of this, it would be promising vii Side effects may be an issue edema noted

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PKC-beta protein kinase C-beta mechanism of action increases new blood vessel formation

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viii These new drugs wont take over in 3-5 years, but in 5-8 years, well see some movement GLP-1: i According to the majority of the audience, once approved, Exenatide will be used in up to 25 of patients with diabetes ii One doctor agreed, while the other thought it could be used in a whopping 5175 of patients with diabetes iii Clearly anything close to 25 share would be a major hit, to say nothing of the higher percentages iv Both doctors felt that the LAR was likely to at least modestly improve efficacy, convenience, and market penetration v As more and more patients go on insulin, more may choose GLP-1 after its approved, due to potential weight loss, versus
weight gain vi Regarding prospects for Novos NN2211, the doctors felt this was probably a good drug, and pointed out that Novo is a potent marketer vii Despite the promise, daily shots are still an issue Dr King noted that this is a behavioral issue for some patients; once they progress to shots, they feel they have a serious disease there can be many cultural barriers DPP-IV: i Both doctors felt that inhibition of DPP-IV would probably not prove to be a more effective and safe method of regulating GLP-1 than administering a GLP-1 analog, while 59 of the audience thought that it would or probably would ii The doctors were split on whether Novartis or Merck had the more promising compound the audience voted for Novartis, 4-to-1 iii Novartis is about to go to phase 3, and go head to head trial with some unnamed agent, looking for equivalency If this happens, theyll be ahead Ruboxistaurin: i The doctors both felt that Lillys would gain approval for neuropathy and ophthalmology applications, but not necessarily for nephropathy ii The neuropathy study should be done in 2004 iii JJ, it was said, is working on a compound in this area, as is Novartis, and there may even be a fourth
Insulin: i We will see more and more insulin use here in the US, said Dr Clark In Europe, about 42 of type 2 patients use insulin, compared to 25-27 here, but he believes that Lantus has helped more and more physicians in this country feel comfortable prescribing insulin This makes sense, because theres less hypoglycemia with Lantus, which is a pain in the neck It is also pretty easy to teach and learn, especially once-per-day usage, although it seems there are probably plenty of patients on one shot a day that should be taking prandial insulin, as has been pointed out recently by key thought leaders ii Lantus current share of the insulin market is 22 - both doctors felt this would increase to 25-40 over time Most of the audience agreed i In terms of impact on pump therapy, both doctors said Lantus had no impact on their willingness to prescribe pumps, though 67 of the audience had expected it would have had a moderate impact My take: weve turned the corner on Lantus being a barrier the benefit to getting patients used to basal/bolus therapy now outweighs the belief that Lantus can do everything a pump can do I believe this is because while some patients have uniform basal
profiles, most do not, so problems with Lantus can emerge with dawn phenomenon, exercise, etc No question that Lantus is better than NPH or the other older, less stable insulins, however the product has enabled great strides in diabetes management I also believe, however, that the new smarter pumps, which also happen to be smaller, more aesthetically pleasing, etc, will also prompt greater penetration of this market

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ii On the oral insulin front, various challenges were discussed, including bioavailability/efficacy, dosing reproducibility, speed of onset/duration of action, and long-term safety The doctors were split on what represented the biggest challenge, with one opting for bioavailability/efficacy and the other choosing long-term safety Inhaled insulin: i Both doctors felt that inhaled insulin side effects, including pulmonary function declines, antibody formation, and cough, would delay Exubera approval by 3-5 years Both wanted longer-term data 1 Said Dr Clark: I am not a fan 31-gauge works referring to Becton Dickinsons 31-gauge, nearly painless syringes He added that some
subset of patients will definitely have adverse events, and its not possible to identify that until it happens the implication being theres a decent chance it doesnt happen until after approval, a la Rezulin Long-term fibrosis is difficult to reverse can take 5-10 years 2 Insulin has two types of action, acute and chronic, and Dr King noted that the second one is fairly unpredictable 3 The doctors allowed that it would be a great product for truly needlephobic patients 4 Lilly is in second place in the horse race they are thought to have an advantage in that they already take insulin If Lilly has an effective method, it may have a pricing advantage, because of higher bioavailability It was said that Lilly is trying to convince healthcare professionals that the powder form is a longer acting hormone The highest bioavailability Ive heard of is with Mannkinds inhaled insulin 5 In conclusion, Inhaled insulin is really not a big deal at the major meetings ii The audience was more updated on approval likelihood, though not necessary on uptake: 42 felt the side effect would delay approval by 1-2 years, and 41 thought it would not delay FDA approval beyond 2005 Of the 41 who felt it
wouldnt delay approval, 37 felt that the side effect profile would have a limited impact on uptake, while 63 felt it would have a significant impact iii If proven safe, inhaled insulin would be used in up to 20 of type 2 patients with diabetes in the US, according to the doctors For type 1 patients, one doctor felt it would be used in fewer than 10 of this population, while the other thought perhaps 21-30 would use it Although it may seem counterintuitive that a higher percent of type 1s would use versus type 2s, Dr Clark pointed out that only 26 of the current type 2 population in the US takes insulin far lower than in Europe and expected to move higher in the US according to Dr Clark so even if half this population moves to inhaled insulin thats still only 10-15 of the total type 2 population if these percentages stay constant 35 of the audience felt that inhaled insulin would be used in over 20 of type 2 patient population iv The doctors pointed out that their colleagues do not want to give a new class of drug for which the side effect profile will be uncertain for 10-15 years Misc: Continuous monitoring/LDL/anti-CD3: i While half the audience felt that continuous glucose sensor
technology would likely impact the market in fewer than five years not clear exactly what impact means, but I think most took it to mean a significant share, both doctors felt it would take 5-10 years Both doctors felt it was probably true that continuous glucose sensors would not replace conventional meter and strip testing Just as in todays market, there is room for a number of brands, I think the same will be true once continuous monitoring is proven, and particularly once its reimbursed ii Dr Clark noted that blood glucose monitoring is the most frustrating aspect of diabetes treatment for doctors, as it requires huge motivation for patients

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iii Recent data from the PROVEIT trial showed the lower the LDL, the better Squirrels have LDL of 35 iv On anti-CD3 - the question is: Do these new immunosuppressants last? One sentiment was that they may work for a few months to a year, but the action may not persist — By Kelly Close Company points of note: 1 Medtronic: a No comments on diabetes Is that in itself a comment, some asked? No, a lot just happened at ACC Roughly 90 of the discussion
surrounded CRM, with the rest addressing the vascular business b One interesting albeit highly tangential note was MDTs focus on telemetry The company appears to be making an enormous push into telemetry technology allowing doctors to monitor/adjust CRM devices without the patient visiting the office through Internet/phone line telemetry The company believes this will be a major competitive advantage It is certainly possible that MDT could build on this presumably positive experience and push the telemetry angle into diabetes care; there certainly may be some opportunity/demand for CDEs to monitor patient glucose control on remote basis 2 Eli Lilly: a Ruboxistaurin, or PKC-beta inhibitor, targets underlying microvascular damage associated with microvascular complications, specifically diabetic neuropathy, diabetic retinopathy, and diabetic nephropathy Ruboxistaurins first indication will be for neuropathy; phase 2 data looked good and filing is expected for 2H05 b Cagily, the company noted that its PPAR modulator may have a positive balance between gamma and alpha PPAR receptors, which could allow it to address both insulin sensitivity and lipid metabolism c Least was said about
exenatide, the GLP-1 that is expected to be submitted by mid-year d Humalog reached 10 billion in 2003 Ed note: with the help of price increases 3 Novartis: a Look for filing of Sandostatin LAR retinopathy in 05, and LAF237 DPP-IV in 06 4 Eyetech: a Expecting phase 2 data for diabetic macular edema in mid-04 b The data looks good; importantly, the company has no competition, and to boot, the any improvement in eyesight is meaningful to patients Onward 5 Nektar: a Look for a US filing of inhaled insulin in late 2004 6 Aradigm: a Aradigm clearly believes liquid inhaled insulin formulations are better because results are more consistently reproducible, the aerosol quality is higher, and the formulation is more tolerant of abuse during shelf-time 7 Alkermes: a As expected, Exenatide LAR Phase 2 results will be released in 2H04 The AIR Insulin product is currently in Phase 2 studies in Type 1 patients and partner Lilly will make a go/no-go decision in 3Q04 The powder-based inhaler looks small and elegant, reminiscent of a Flash memory drive Panelists felt that Lilly may have a cost advantage 8 Kos Pharma: a The companys priority is clearly on cholesterol Kos believes an Exubera filing
would ultimately help them by reducing cynicism towards the notion of inhaled insulin, but theyre not looking to file until 2010 At this point, they havent yet completed an in-vivo safety study They clearly want to partner this diabetes drug, and likely will spend little without one Their tight relationship with Takeda may make them natural partners –By Stephen Simpson and Kelly Close

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Appendix C: Obesity Timeline, 2004/US Objects to WHO Plan to Halt Obesity Obesity Timeline, 2004 1 January 5: A study of 6,212 kids aged 4-19 published in Pediatrics by food guru David Ludwig who has done some excellent research pointing to the significance of the glycemic index implies that every day, over 30 of US children eat fast food, which translates roughly to six extra pounds per child per year Consumption was highly prevalent across the US in both genders and all racial/ethnic groups The study abstract notes that children who ate fast food, compared with those who did not, consumed more total energy, more energy per gram of food, more total fat, more total carbohydrate, more added sugars, more
sugar-sweetened beverages, less fiber, less milk, and fewer fruits and nonstarchy vegetables Whew Mid-January: The US officially objects to WHOs plan to halt obesity See below for our detailed, very negative, look at the US perspective January 21: The CDC estimates that obesity cost the US 75 billion in 2002 in avoidable healthcare costs 64 of American adults are either overweight or obese as of 2002, up from 60 in 1990 An alarming 31 of the adult population is obese, up from 20 in 1990 a Tangent on type 2 in kids: In Houston, as of 1995, more than 95 percent of all childrens diabetes were type 1 cases In 2003, the number of type 2 cases accounted for 31 percent of all childhood cases at the Texas Childrens Hospital, said Dr Siripoom McKay in a recent Houston Chronicle piece February 24: The journal Surgery estimated there are 5,324,123 people, or 28 of the American population, who are eligible for obesity surgery Of these 38 rely on Medicare or Medicaid for their health insurance Of the 28,590 gastric bypass operations performed in 2000, only 13 of patients used Medicare or Medicaid to pay for the operation A significant fraction of the American population could potentially
benefit from obesity surgery However, many of those individuals are black, poorly educated, and impoverished Public assistance programs need to account for these patients Centers performing bariatric operations need to accommodate the educational and financial constraints these patients have when planning long-term postoperative care March 2: McDonalds caves, says it will cease supersizing Hooray Lets make this a national holiday For perspective, keep in mind that the average Coca-Cola size in the 1950s was 6 oz, in contrast to todays super-sized 64-oz soda March 10: The US House of Representatives voted to ban lawsuits against the food industry for obesity claims, squashing the likelihood of class action lawsuits that contend food companies are responsible for increased obesity March 10: No kidding, the same day, obesity expert Mokdad published in JAMA estimating 400,000 deaths from obesity in 2000, the 2 cause of death, just shy of tobaccos 435,000 level So guess which grew 9 and which grew 33 in just over a decade? Mokdads persuasive piece calls for a more preventive orientation to healthcare in the US stay tuned March 11: So, I was positive this was a joke, but apparently not
Krispy Kreme will offer a lowsugar donut for dieters and diabetics Note they didnt go into this on their March 10 webcast March 12: The FDAs overdue report on obesity Calories Count emerges, or as the website proudly announces, the agencys strategy is unveiled More on our dim view in Appendix A — By Kelly Close

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US Objects to WHOs Plan to Halt Obesity In the face of a growing obesity and diabetes epidemic, the US opposed the World Health Organizations strategy to halt and prevent the rise of obesity and diabetes worldwide During a meeting earlier this year, the 32-nation executive board of the WHO released a preliminary report that called for two primary changes: 1 the food and beverage companies reduction of fat, salt, and sugar content in their products, and 2 the restriction of food advertising aimed at children Specifically, the WHO and the Food and Agriculture Organization recommends that no more than 10 of a persons daily caloric intake be from added sugars, fat intake should be limited to 15 - 30, and saturated fats should make up less than 10 Additionally, the WHO and FAO report recommends one hour of moderate exercise per day

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Though the WHO member nations plan to formally adopt the strategy in May, the US objected, delaying the final version for at least another month by asking for more research The US questioned the scientific basis of linking fruit and vegetable consumption to decreased risk of diabetes and obesity, and argued that little research exists to support the recommended amount of exercise Several other countries, including Pakistan, South Korea, the Philippines, and Cuba, whose major industry is sugar, backed the US position The United Kingdom, Canada, and a number of European countries on the executive board opposed the US The Bush administration claims genuine doubts about the scientific validity of the councils recommendations and firm convictions that individuals remain responsible for obesity However, many skeptics contend that the administration is more focused on ingratiating itself with the powerful sugar industry, which provides substantial campaign funding and votes in key election states, including Florida The protests of the US have been criticized as a stalling tactic often used by food and beverage companies
that call for more research to delay changes Though the strategy would not be binding, many countries would use it as guideline for their own food policies Other critiques of the US cite the fact that the food and beverage industries are major political donors that could influence the next presidential election Additionally, US multinational companies whose major profits are from overseas may be threatened by a downward turn in marketing and sales of their foods The Health and Human Services and National Institutes of Health argue that the US is trying to strengthen the WHOs strategy by making it more accurate in its recommendations and restrictions Specifically, the NIH criticized the WHO report for not being specific enough by advising people to eat more fruits and vegetables in the place of less healthy foods, not just increasing consumption of fruits and vegetables Reports of the WHO on food and sugar consumption have been vehemently opposed by food and beverage companies in the past; though this time around, groups such as the Grocery Manufacturers of America whose members include Coca-Cola, PepsiCo, and Hershey, claim they support the fight against obesity Yeah, right A
conflict of interest? Florida Crystals Corporations Jose Pepe Fanjul has raised at least 100,000 for Bushs presidential re-election campaign, J Nelson Fairbanks, chief executive of US Sugar Corp, earned Pioneer status for raising at least 100,000 for Bushs 2000 campaign, and Cargill chief executive Warren Staley is a Pioneer for the 2004 campaign In an election year, Bush is certain to win the favor of industry and to keep the economy going at all costs, including health costs In fact, Bushs conviction that high caloric intake will keep Americas economy ablaze is most vividly demonstrated in a quote published in the Jan 31-Feb 6 2004 edition of The Economist: You [addressing David Gregory of NBC] get paid a lot of money; you ought to be buying some food here Its part of how the economy grows Youve got plenty of money in your pocket, and when you spend it, it drives the economy forward So what would you like to eat? Apparently, Bush equates the rate at which America stuffs its face with food with the growth of the US economy, ignoring the massive financial burden of obesity on the entire country not only on the ill, but on the corporations whose workers miss more sick days and on
the millions who shoulder the burden through rising health insurance costs According to HHS special assistant for international affairs William Steiger, who is representing the US at these WHO roundtables, Bushs chief objection involves the principle of shifting responsibility for the surge in obesity from an individual failure to exercise to recommending that government and industry assume a more proactive role in alleviating this great health burden Alongside the US, Russia, India, and sugar-producing nations Mauritius and Grenada also oppose the WHO proposition Although the WHO document does not mandate any direct government actions per se, public health workers believe the statement would greatly empower their efforts to recruit government action in the fight against obesity for example, restricting advertising of junk food or taxing it

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The WHO proposal reflects the growing recognition that such chronic illnesses as diabetes and cardiovascular disease are no longer luxuries of the rich developed world In fact, populations in developing regions may be at even greater risk from
high-calorie diets and sedentary lifestyles because they carry thrifty genes that predispose them to gaining weight during times of high availability of food The WHOs scientific report drafted by 36 of the worlds experts in activity and nutrition warned that India would have one of the worlds highest rates of type 2 diabetes by the year 2025 Having declared the fight against obesity one of his agencys top national priorities, and even promising to slim down himself to lead the crusade, HHS Secretary Tommy S Thompson now finds himself in a rather awkward position that has elicited wide criticism For example, Bruce Silverglade of the Center for Science in the Public Interest, a Washington-based consumer group ripped, What were surprised about is that Secretary Thompson, who has espoused so much concern about obesity, is privately working with representatives of the food industry to derail [this] initiative Professor Kaare R Norum of the Institute for Nutrition Research at the University of Oslo, who chaired WHO scientific advisory panel, already has drafted a scathing letter to Thompson attacking the US position Thompson seems to have been pressured by the food industry, the White
House, as well as the Senate Senators Larry Craig and John Breaux, cochairmen of the Senate Sweetener Caucus, asked Thompson to instruct WHO to cease further promotion of the report The food industry, through its powerful ties to the US Senate, even has threatened the WHO with withdrawal of the 416 million sum the US contributes to it each year The WHO votes on a final draft of the proposal when it reconvenes in May In the meantime, the Bush administrations contention that the WHO recommendations rest on shaky evidence certainly is bound to further fuel diet wars over what people should really eat and what role governments should play in protecting the public and particularly children from the influences of the food industry With at least 300 million adults clinically obese worldwide, the WHO continues to work on a final plan to be formally adopted by May — By Martha Nelson, Janet Ng, and Kelly Close

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Appendix D: Media Roundup 1 Improved Glucose Excursions Using an Implantable Real-Time Continuous Glucose Sensor in Adults With Type 1 Diabetes: DexComs first peer-reviewed published
results appear in the March Diabetes Care The data clearly showed that continuous monitoring enabled more time spent in euglycemic range music to the ears of patients with diabetes Euglycemia is one of those novel concepts that most patients with diabetes would probably say they could never really fully achieve, certainly not with any consistency Heres hoping that with TheraSenses Navigator already at the FDA, with Medtronics Guardian 2 to be submitted shortly thereafter they have promised by end of April, and with DexCom leading the implantable front, were at the start of a new era All the excitement aside and I do think its extremely exciting, as profound change in diabetes care could stem from this new technology the FDA doesnt appear to be moving particularly quickly on any diabetes front these days eg, Detemir, Symlin, CozMonitor, and reimbursement that black box always seems to take longer than it seems it ought to Its tough to prescribe unless its reimbursed, but it wont be reimbursed until CMS sees a lot of experience with new products circular? Editorial, The Need for Separate Performance Goals for Glucose Sensors in the Hypoglycemic, Normoglycemic, and Hyperglycemic
Ranges: This piece by Dr David Klonoff is an important read for anyone following continuous monitoring A companion piece to the DirecNet piece in the same issue of Diabetes Care, it makes the point that GlucoWatch and CGMS do not reliably detect hypoglycemia in kids and teens and that all monitors perform worst in the hypoglycemic range Klonoff emphasizes that both episodic and continuous glucose monitors may detect hypoglycemia less accurately than many clinicians realize and that real-time continuous glucose monitor performance need to be closely scrutinized in the hypoglycemia range in particular Super Size Me Super Size Me, the buzzed-about Sundance prize-winning documentary wwwsupersizeme about filmmaker Morgan Spurlocks personal experience of the physical deterioration brought about by a month of consuming fast food three times a day As a result of the experiment, Spurlock gained 25 pounds over the month, while his total cholesterol level soared from 165 to 230 Super Size Mes domestic theatrical and home video rights were recently sold to Roadside Attractions and Samuel Goldwyn Films, and the film is now set to hit nationwide theaters in May At the 2004 Sundance Film
Festival, the film earned Spurlock the documentary directing award for the way he pretty ingeniously juxtaposes the films entertaining element with the dark, sobering results of his astonishingly rapid physical decline, which included vomiting, headaches, depression, and other signs of physical and mental deterioration The inspiration for Spurlocks month-long, 20-city Super-size journey came from viewing a television clip in which two teenage girls were suing McDonalds for their obesity This question of personal responsibility versus corporate responsibility represents a central issue in the film Corporate deceit takes the brunt of the blame in the film, and the documentarys main shortcoming could be its rather reductive message that eating junk food is the sole cause of obesity Another shortcoming could be the filmmakers methodology: essentially any food eaten to excessive consumption could cause gastrointestinal problems Thus, the main point of the film is not to condemn the fast food industry per se, but to criticize the way it markets itself for excessive consumption Spurlocks message derives much of its potency from a clever use of images that juxtapose fast foods happy image
against its grimmer reality For example, Spurlock split-screens a smiley Ronald McDonald commercial against Curtis Mayfield singing his classic Pusher Man In another powerful image, he shows a colorful map of Manhattan with 83 flags crowded into the 14-mile island, each of which represents a McDonalds location Truly horrifying Spurlock also inserts vignettes of interviews with people on the street, the US surgeon general, and a fast-food industry lobbyist in between his gorging and vomiting

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So, look for Super Size Me appearing soon in theaters But be prepared: you may not want to include an extra large butter popcorn and super-sized soda as part of your viewing pleasure Instead, order a childs diet soda 16 ounces or better yet, sneak in a bottle of water Before Super Size Me is released commercially, it will be shown at the San Francisco Film Festival April 24 Were buying a block of tickets so let me know if you will be in town and would like to come The film will also be shown in Austin this Friday, March 19 http://wwwsxswcom and in Durham on April 3
http://wwwfullframefestorg/2004new_docs_listcfm Morgan Spurlock, by the way, sounds very cool He was born in West Virginia and is a graduate of New York Universitys Tisch School of the Arts He has written and directed shorts, music videos, and plays and this is his first feature film — by Martha Nelson and Kelly Close

Diabetes Close Up is a newsletter highlighting notable information and events related to selected companies with diabetes/obesity businesses This newsletter is put forth as an unbiased commentary on the industry If you have any suggestions or comments regarding content, please contact info@closeconcernscom If you would like to 1 unsubscribe; 2 receive a monthly digest rather than realtime updates; 3 add a name to the DCU mailing list; or 4 offer any suggestions or comments regarding content, please contact info@closeconcernscom Disclosure: Kelly L Close is a specialized consultant to the medical technology/pharmaceutical/biotech industries Companies 1 in which Kelly Close has a personal investment; 2 that are clients of Close Concerns, Inc; and/or 3 on which Kelly Close serves on a speakers bureau, including Abbott, Animas, Amylin, Aventis, Inamed, Johnson Johnson,
and TheraSense All observations expressed are the opinions of Close Concerns alone and should not be viewed as recommendations to investors on any companies in the industry

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