Our team just returned from a fantastic week in awesome Austin, and here we bring you our top takeaways from the final days of the 26th annual AACE Scientific and Clinical Congress. Many thanks and congrats to the organizers. See below for updates from Tandem and TypeZero, Dr. Alan Garber on the level of evidence for the cardioprotective benefit of GLP-1 agonists vs. SGLT-2 inhibitors, Dr. Timothy Garvey on AACE’s new name for obesity (adiposity-based chronic disease, or ABCD) – plus much, much more. Also check out our past coverage of days #1 and #2. We’re already counting down the days until AACE 2018 – May 16-20 in beautiful Boston, MA!
Top Diabetes Technology Highlights
1. Medtronic Global Medical Director Dr. Scott Lee shared how he explains the 670G value proposition to patients, excellent safety data from the continued access phase, and some of the positive feedback he’s heard from patients. We were quite moved when Dr. Lee commented that speaking to a nocturnal hypo-prone patient in the pivotal study about the overnight benefits of the 670G was “remarkable” and “one of the most moving experiences in [his] 20 years of practicing diabetes.
2. At a sponsored dinner, Tandem management shared that the t:slim X2-Dexcom G5 integration could be approved by FDA “very shortly”/“any day now.” Notably, we also learned that the t:sport patch-like durable pump is still in development, with plans to integrate advanced algorithms. Good news for everyone on this front.
3. At a Tandem-sponsored dinner, TypeZero CMO Dr. Daniel Cherñavvsky provided an encouraging look at the startup’s pipeline, including the first trial timing we’ve heard for the inControl Advice advisor (type 1 trial to begin in 2Q-3Q17; type 2 trial to begin in 1Q-2Q18) and population risk analysis remote care platform (trial to begin in 2Q18). We are particularly moved on the type 2 news.
4. Former FDA Commissioner Dr. Robert Califf delivered a plenary in front of a packed house on Saturday in which he explained why the FDA is so overburdened, elaborated on the “information revolution” in healthcare, and gave new details on Verily’s Project Baseline study.
5. Former AACE President Dr. George Grunberger highlighted the hot off the press Endocrine Practice Letter to the Editor in which he and Tulane’s Dr. Vivian Fonseca provide a follow-up to last year’s AACE CGM consensus conference with two recommended standard reports, as well as a third exhibit with additional suggested (non-standardized) CGM reports.
Top Diabetes Therapy Highlights
1. AACE/ACE diabetes guidelines committee member Dr. Alan Garber expressed his view that the evidence for cardioprotective benefit is stronger in GLP-1 agonists than in SGLT-2 inhibitors, given that two CVOTs has demonstrated benefit for GLP-1 agonists. Overall, he suggested that “additional studies will be necessary before we can go out whole hog for a single drug or even a single class of agents.”
2. In a deep-dive session on the renal effects of SGLT-2 inhibitors, both Drs. Ralph DeFronzo and Matthew Weir were extremely positive about the renal benefit of these agents and expressed strong confidence that the benefits extend to all members of the class.
3. Dr. Sue Kirkman discussed the treatment of type 2 diabetes in older adults, ultimately emphasizing her view that the strategy to treat diabetes is more important than the actual A1c target in these patients.
4. Through a comprehensive overview of the research connecting type 1 and type 2 diabetes to bone fracture risk, Dr. Clifford Rosen wove in some commentary on how different diabetes drug classes impact bone. He suggested that DPP-4 inhibitors may improve fracture healing, while insulin has neutral effects on the skeleton and insulin-sensitizers like TZDs require more evaluation. He refrained from sharing any specific details on SGLT-2 inhibitor Invokana (canagliflozin) and its association with bone fractures – “I can’t tell you about it. You’ll have to wait until CANVAS presents at ADA.”
5. Less than 24 hours after the US House of Representatives passage of the American Health Care Act (AHCA), Ms. Jill Rathbun, a managing partner at Galileo Consulting Group, offered her take on what the next few months of the Trump Presidency might mean for healthcare. Providing an overview of the litany of changes in the law that will very likely translate into reduced health coverage overall, she framed the Trump Administration’s healthcare efforts with one concept: Less. “This administration is really about ‘less,’” as she put it, “Sometimes less is more and sometimes less is just less.” Despite the bleak outlook on healthcare as the AHCA is written, Ms. Rathbun offered some hope by emphasizing the long road and challenges the bill must navigate before it is signed into law.
Top Obesity Highlights
1. In a poster, a sub-analysis of people over 65 in the Novo Nordisk-sponsored ACTION study described the experience of obesity in older Americans: they are diagnosed with obesity less frequently despite having more complications, and seek less support from physicians and yet succeed at weight loss more often. Additionally, a greater proportion of older people with obesity reported that a specific medical event (heart attack, stroke, etc.) had a profound influence on their desire to manage weight and cited improving existing health conditions as an overall goal to achieve as part of weight management.
2. Dr. Timothy Garvey reviewed the recent AACE position statement on obesity, which proposes a new name for the medical condition – adiposity-based chronic disease (ABCD). We’re encouraged to see AACE stepping up with clear obesity treatment guidelines as well as this effort to medicalize the term. ABCD combats stigma and unconscious provider bias.
3. In a very actionable talk, the always-engaging Dr. Lee Kaplan (Harvard Medical School and Massachusetts General Hospital, Boston, MA) presented an overview of his core principles for obesity treatment.
4. In a highly-entertaining talk, Dr. Tim Harlan (Tulane University, New Orleans, LA), a chef and restaurateur turned physician, provided a fascinating overview of his “culinary medicine” approach to obesity.
Top Diabetes Technology Highlights
1. Dr. Scott Lee: 670G Auto Pilot at Night, Co-Pilot during Day; 630G->670G Training Protocol
Medtronic Global Medical Director Dr. Scott Lee shared how he explains the 670G value proposition to patients, excellent safety data from the continued access phase, and some of the positive feedback he’s heard from patients. The importance of effectively communicating the role of the 670G to patients can’t be understated, and to ensure the average person gets it, Dr. Lee resorts to metaphors. He compares the PID algorithm to cruise control, and tells patients that the system works like auto pilot at night, while it is more of a co-pilot during the day. We like this idea, as it emphasizes that the patient still has to drive – give insulin with a meal, respond to hyperglycemia, check blood glucose, etc. – but the 670G will provide some daytime guardrails in the background, forgiving carb-counting inaccuracies, stress, high-fat meals, etc. In the continued access phase, Dr. Lee emphasized that there have been zero episodes of DKA and only two (!) episodes of severe hypoglycemia, both unrelated to closed loop (i.e., large boluses while in open loop). The safety profile of this device is definitely solid (especially compared to nothing), and on AACE Day #1, Dr. Bruce Bode shared encouraging efficacy data from ~560 patients via CareLink (average glucose=151 mg/dl; standard dev=52 mg/dl – a standard deviation less than 50% of the “average” is typically seen as very good so a standard deviation less than 35% of the average is quite notable). Notably, Dr. Lee also commented that speaking to a nocturnal hypo-prone patient in the pivotal study about the overnight benefits of the 670G was “remarkable” and “one of the most moving experiences in [his] 20 years of practicing diabetes.” We were very moved by this - we’d love to see more moments of success for providers. Dr. Lee’s then said that traditional pump therapy seems “pretty crude and rudimentary” next to the automatic micro-doses the 670G provides every five minutes. “The most common clinical conundrum we see is patients doing the same thing every day and having very different day-to-day outcomes, and this helps address that problem for the first time.” The most important aspect of the 670G for patients he’s spoken to? It accommodates around imperfections, human-ness, allowing them to not feel guilty if they misestimate a bolus. This early feedback was very illuminating and reinforces our view that eventually, anyone on mealtime insulin should have the help of a computer – bolusing “in the wild” unaided by technology will thankfully become less and less common.
- Texas Diabetes and Endocrinology’s Dr. Thomas Blevins gave his account of the 670G training process in his clinic; see image below for protocol, which is the same that Yale’s Dr. Jennifer Sherr spoke about at CDTM. Dr. Blevins has only had patients on the system for three to four weeks, but he characterized training as straightforward, and his patients, who come into the office two at a time, picked it up well, he said. On the whole, he called 670G “one of the nicest developments in diabetes that [he’s] seen in [his] 30 years practicing. Notably, one of the slides characterized use of “close follow-up” as a the key to success, and it will be interesting to see how scalable this device is for the average diabetologists. How easy will it be to prescribe and train once it is more broadly available?
2. Tandem t:slim X2 with G5 approval “any day now”; t:sport still in development, plans to integrate advanced algorithms
- Tandem management shared that the t:slim X2-Dexcom G5 integration could be approved by FDA “very shortly”/“any day now.” Per the 1Q17 call, approval was expected by this summer and Tandem planned to launch this product within 30 days of approval. Subject to approval, current t:slim X2 users (10,000+ patients) will be able to update their pump’s software for free to add G5 integration (via the Tandem Device Updater). We think patients and providers will be thrilled by this capability. EVP Mr. Brian Hansen reiterated that this update will be free, but the company is unsure if the same will be said about the PLGS (launch expected early 2018) and hypo-hyper minimizer (launch expected by the end of 2018) systems. However, if they are not free, they will likely be “in the $199-$299 range, not in the thousands.” We’re glad to hear this, since many t:slim X2 customer would be frustrated to hear of a significant upgrade fee. That said, it’s a far cry from the costs of old to upgrade with many other systems.
- Tandem is “working on embedding advanced algorithms” in the t:sport patch-like durable pump, which is still in development. This is the first allusion to the pump (~50% smaller t:slim, worn on the body, short infusion set, no screen or buttons, wireless controller) since 2Q16, when management pushed PMA submission timing back to 2018 due to upcoming R&D work on the t:slim X2 with Dexcom CGM integration and automated insulin delivery. We were surprised to hear this mentioned, given the pressure Tandem has to execute on its current pipeline; perhaps we’ll hear an update on the next call. While the t:sport doesn’t match Insulet’s truly tubeless OmniPod, it would certainly bring a more competitive product for Tandem to court MDIs and differentiate from standard durable pumps.
3. TypeZero inControl Advice/Remote Care Platform Trial Timing, Planned Studies, and Closed Loop Future Directions
At a Tandem-sponsored dinner, TypeZero CMO Dr. Daniel Cherñavvsky provided an encouraging look at the startup’s pipeline, including the first trial timing we’ve heard for the inControl Advice advisor to inform open-loop insulin dosing (type 1 trial, n=142, open for enrollment; type 2 trial to begin in 1Q-2Q18) and population risk analysis remote care platform (trial to begin in 2Q18). Dr. Cherñavvsky, who also holds an appointment as an assistant professor of the Center for diabetes technology at the University of Virginia, spoke about a truly impressive breadth of ongoing or planned closed loop clinical trials:, adjunctive inhaled insulin (Afrezza) with closed loop (starting soon, collaboration between Yale University and the University of Virginia), fixed dose insulin/pramlintide mixture in closed loop (collaboration between Mayo Clinic’s Dr. Ananda Basu and UVA), physical activity informed closed loop (in collaboration with Dr. Marc Breton at UVA, and surely many more. Of course, there’s also the NIH-funded iDCL study, which is in the training phase and doubling as Tandem’s pivotal study, Project Nightlight (n=84, 11 months of closed loop vs. SAP), and Safety at Home (n=22, five months of use). Notably, the iDCL is designed for patients ages 14+, but the University of Virginia Center for diabetes technology has also submitted a grant application with NIH for adding pediatric patients ages 6-13, which (if funded) would also be in collaboration with TypeZero. Thanks to its UVA ties, this company is extremely prolific when it comes to generating clinical data – on top of the aforementioned studies, the TypeZero system has been tested in more than 42 trials since 2006, amounting to ~300,000 collective hours (>30 years) of closed loop! Read on for a list of TypeZero’s closed loop future directions, t:sport, inControl Advice and Remote Care Platform, and more!
- No avenues are off-limits in terms of future directions for TypeZero’s algorithms, devices, cloud usage, and hormones. Dr. Cherñavvsky displayed slides depicting the following potential future directions – since TypeZero now has a partnership with Cellnovo as well, these could apply to Cellnovo and/or Tandem:
- Algorithms: Activity/exercise/sleep detection based on accelerometer or heart rate monitor; goal-oriented algorithms (user-selectable targets and thresholds, turning modules off and on); tunable algorithms that can be more or less aggressive; real-time estimation of insulin-sensitivity; and personalized algorithms that adapt to a patient’s individual, evolving physiology.
- Devices: New sensors (Senseonics’ Eversense and Abbott’s FreeStyle Libre specifically called out); occlusion detection (JDRF grant proposal already submitted with Dr. Claudio Cobelli, as principal investigator in collaboration with UVA and TypeZero) modularity (swap pumps/sensors as needed); and integrated or standalone accelerometers.
- The cloud: Semi-automated therapy optimization under the guidance of a physician; machine learning and AI tools to support personalization; and improved meal input through natural language processing and text input (in example working with Amazon Echo and Google so meals can be literally announced).
- Hormones: Basal and bolus insulin; amylin for post-prandial control; glucagon for hypoglycemia rescue.
- TypeZero CSO Dr. Patrick Keith-Hynes introduced the inControl projects at DTM 2016 (including screenshots): InControl Advice is a smartphone app that provides open-loop insulin dosing advice and pattern recognition for those on MDI or pumps and CGM (including smart bolus calculator physical activity advice, interactive risk monitoring, and clinician messaging via a chat-based interface), and inControl Remote Care Platform is a tool for clinicians to optimize insulin pump or MDI therapy. The platform conducts risk-based therapy optimization using 2-4 weeks of CGM, BGM, and meal data to propose changes in insulin therapy, including basal, carb ratio, and correction factor. These tools could be tremendously useful for saving physician time while improving patient outcomes in a scalable way, especially for those who can’t afford or are not interested in closed loop systems.
4. Former FDA Dr. Califf Explains Why FDA is So OverBurdened, and Discusses “information Revolution” and Verily’s Project Baseline
Former FDA Commissioner Dr. Robert Califf delivered a plenary in front of a packed house on Saturday in which he explained why the FDA is so overburdened, elaborated on the “information revolution” in healthcare, and gave new details on Verily’s Project Baseline study. It is widely held that FDA is under-staffed, and the former Commissioner has seen it first hand: “Sometimes FDA appears to be slow because our people are doing so many other things that you may not realize.” Tobacco, food supply safety and security, cosmetics, veterinarian medicine, and even counterterrorism (of the biological and chemical varieties) all fall under FDA’s domain, in addition to medical therapies and devices. On a much more positive note, Dr. Califf has seen a revolution in healthcare during his career – a halving of CV death risk, plus a number of exciting drugs and devices – and the next revolution, in his opinion, will result from the transformation of information, something he has championed tirelessly. Currently, there exists tons of data, and hoards of information go into computers, but so little insight comes out – Dr. Califf pointed to the facts that the average doctor spends 2.5 hours in front of the computer for every hour with patients, and that <15% of major clinical decisions are supported by solid evidence. The former stat is even more harrowing than one from a February JAMA Viewpoint on physician burnout, which estimates that physicians spend approximately 33% of their work hours performing direct clinical work vs. 49% completing clerical tasks and interfacing with the EHR. Dr. Califf referenced many of the positive information aggregation and integration efforts currently ongoing: NEST (National Evaluation System for Health Technologies; aims to track medical device data and patient-reported outcomes through the use of real-world evidence); PCORnet (“we’re about to launch a very active phase of this”); and the NIH Collaboratory (“brings the cost of conducting trials from $150 million to $5-$15 million). At the end of the day, data collection infrastructure is imperative, but with the quantity of information increasing exponentially, the key is to detect signals amongst the noise and generate insight whenever possible. In Dr. Califf’s wise words, “the best technology is good information. If we don’t figure out how to deal with it, it could be overwhelming and do more harm than good.”
- According to Dr. Califf, the Verily Project Baseline study population (a deep dive into human physiology and behavior that kicked off recently), will be enriched for those at risk of breast cancer, ovarian cancer, lung cancer, and cardiovascular disease, and will generate six terabytes(!) of data per visit. While the latter statement generated an audible “Oh my god” from the audience, we were more psyched to hear that cardiovascular disease will be a major focus of the study, considering the degree of comorbidity between CV risk and diabetes.
- “Up until now, because of the limits of computation data storage and analysis, we’ve all been like the blind people and the elephant. We’ve all seen the part of human we’re interested in, not the whole picture.” The hope is that Project Baseline will help zoom out and bring a more holistic picture.
- “Activated patients are critical for diabetes, cardiovascular disease, pulmonary disease. There is already good patient advocacy, but it doesn’t have the same impact as advocacy for rare diseases or cancer. I don’t want to diminish the advocacy for those diseases, but as a society with fixed resources, you would be well served to help patients organize better when it comes to which therapies are developed and paid for.”
- “It would be good if every part of medicine could be like Google search, connected to every other thing so we know everything about that patient. Also, whenever we do a Google search, we’re participating in on average 10 clinical trials [A/B testing]. They wouldn’t think about changing anything without testing it rigorously first, yet in medicine, it’s special to randomize.” While clinical trials are still the standard, we’re hopeful that registries and large health systems will be able to provide settings for pseudo-randomized trials, where patients are “randomized” to different therapies and use them in the real-world.
- “We are faced with an exciting set of opportunities in science and medicine, but there are probably a lot of problems we aren’t prepared for yet.” Dr. Califf specifically referenced the Precision Medicine Initiative (PMI), complex regenerative medicine, and CRISPR/Cas9 gene editing.
- On the PMI, he polled the audience “how many of you are ready to deal with whole genomes in your EMRs?” So little is known about the significance of genetic variations, and with whole-genome sequencing dropping in cost rapidly and no limit to EMR storage, physicians could be faced with human genomes and metagenomes (resident bacteria included!) in the near future.
- Dr. Califf recalled that all in one day, the plant side of FDA, animal side, and human side of FDA briefed him on the potential of CRISPR/Cas9 gene editing. The plant side told him it could fix global hunger, the animal side said that animal models of human disease could do wonders for research (he also claimed that bacon grown in a dish tastes pretty good), and the human side said that there are 5,000 diseases with no treatment, and gene editing could hold the key.
Questions and Answers
Dr. R. Mack Harrell (Memorial Healthcare System, Hollywood, FL): We’ve gone through a 20-year phase of registry development, and the era seems to have come, so maybe it’s possible for small organizations like ours to enter it. What opportunities do you see for us to get on the board early?
Dr. Califf: It would be a big mistake to try to copy the strategies of decades ago. The organizing principle will be the integrated health system. Specialty societies should own the use of broader information capabilities to answer questions pertinent to patients, not create data.
Dr. Harrell: Hoards are still doing private practice, and they’re nervous about how they can survive and use information in the future.
Dr. Califf: [Venrock’s] Dr. Bob Kocher would be worth googling if you’re in that situation. He was part of the ACA, and has recently taken the position that small practitioners should band together into federations that share information. Learning increasingly will be done though machine learning, you can’t do that as an individual. In imaging especially, machines outperform radiologists hands down for static images. You still need the radiologist, but they now need to decide what to do with the computer’s diagnosis.
Dr. Harrell: What are your thoughts on IBM Watson?
Dr. Califf: Like most of this stuff, the hype greatly outdid the performance at the start. But all of Silicon Valley has failed in healthcare almost 100% of the time. We’re complicated, the current president found that out. I’m not giving up on Watson, it can do some things really well, but coming back to curation of information. One thing systems should be good at is serving up good information – one of the problems with Watson is if you put garbage in, you get garbage out. The most valued person in Silicon Valley is the data janitor who curates data.
5. AACE’s Recommended Standard CGM/BGM Reports Published in Endocrine Practice
Former AACE President Dr. George Grunberger highlighted the hot off the press Endocrine Practice Letter to the Editor in which he and Tulane’s Dr. Vivian Fonseca provide a follow-up to last year’s AACE CGM consensus conference with two recommended standard reports, as well as a third exhibit with additional suggested (non-standardized) CGM reports. The reports are essentially modified Ambulatory Glucose Profiles, with the first designed for CGM, and the second for BGM. Both have a top line containing information about usage/frequency of testing, with a dashboard below containing average glucose, eA1c, time in range, coefficient of variation, and standard deviation. Below the dashboard is the IDC-developed AGP, with the median glucose trace surrounded by clouds indicating 10-90 percentiles and 25-75 percentiles. The recommendations in the third figure were derived from last year’s AACE/ACE Consensus Conference on CGM, where CGM thought leaders convened to discuss data reporting, among other hot topics. Included in the list of recommendations for non-standardized reports, which are intended to be tailored to the individual clinic, are: (i) Individual daily tracings; (ii) pattern identification for hypoglycemia, hyperglycemia, and glycemic variability; (iii) glucose tracing that integrates logbook information; (iv) detailed information on the number of hypoglycemia events, duration and timing; (v) hypoglycemia reported <55 and <45 in addition to <70; (vi) risk indices – measures of frequency and extent of low and high blood glucose; (vii) post-meal glucose summaries; (viii) summaries of log book averages; and (ix) number and timing of calibrations (if applicable). We are delighted to see this guidance from AACE, and hope that manufacturers will continue to adopt the report as Abbott, Roche, Glooko/Diasend, Tidepool, and others have already done. As Dr. Grunberger always says, when cardiologists look at EKGs, they’re first question is never “which device did this come from?” – everything is immediately decipherable regardless of manufacturer, and glucose reports should be as universally understandable and “glance-able” as an EKG. This was the strongest call we’d heard yet for CGM data to be defined and measured consistently, and we believe patients would benefit profoundly from this approach – here’s to leadership from Drs. Grunberger and Fonseca.
- “Having FreeStyle Libre Pro in the office has truly, truly changed the way I and my patients think about diabetes. Isn’t it fun that this technology is finally hitting the market?” Dr. Grunberger isn’t the first to express the “how did we get along without this?” sentiment, but it is so impactful coming from a physician who has been caring for people with diabetes for multiple decades.
- “The plea has been expressed by many patients, even regulators – just get away from this A1c-centric culture. Practitioners get graded on A1c. I can get all patients’ A1c lower than 6%, and probably half would survive. And it’s the whole stupidity of relying on A1c to dictate care.” Following the highly successful FDA Workshop on Outcomes Beyond A1c in August, we look forward to future gatherings that discuss ways to move the needle away from sole focus on A1c and toward metrics such as time in range, hypoglycemia, and patient-reported outcomes that also incorporate A1c but contextualize it. We know a session at ADA will address this topic, as will other efforts ongoing in the community (e.g., JDRF’s T1D Outcomes program). “We need better codes, how we get paid for expertise. We can figure out what’s going on in a fraction of a minute, but I’m not sure anyone understands the effort that goes in [to the entire process]. It’s incredibly labor-intensive. If you did in-depth analysis every day, maybe you’d see one patient a day.” We second this – there are so much better payments for analysis of heart disease and we hope this can be extended to CGM. Our sense is also that the codes that do exist aren’t well understood enough or optimally used and we hope to see improvement on this front.
Top Diabetes Therapy Highlights
1. Dr. Alan Garber: AACE Guidelines and Positive CVOTs
During a Sanofi-sponsored corporate symposium, Dr. Alan Garber expressed his view that the evidence for cardioprotective benefit is stronger in GLP-1 agonists than in SGLT-2 inhibitors. In response to a question on when the AACE/ACE diabetes treatment guidelines might incorporate the data from EMPA-REG OUTCOME and LEADER trials demonstrating a cardioprotective benefit for SGLT-2 inhibitor empagliflozin and GLP-1 agonist liraglutide, Dr. Garber suggested that more evidence is needed. He emphasized that the EMPA-REG OUTCOME findings in particular were very surprising, without a demonstrated benefit on more traditional atherosclerotic endpoints (MI and stroke) despite strong results on reduction of death. As such, he stated, “Additional studies will be necessary before we can go out whole hog for a single drug or even a single class of agents.” On the other hand, he expressed somewhat more confidence in the cardiovascular benefit of GLP-1 agonists, given that results from two trials indicate a strong benefit: LEADER and SUSTAIN 6 (though he acknowledged that SUSTAIN 6 was designed as a safety study). Overall, however, Dr. Garber suggested that more trials and data may be necessary before a substantial change to the guidelines. Clearly, between his comments and those of Dr. Daniel Einhorn the day before, there is quite a lot to think about and consider in terms of potential changes to guidelines – this is likely true for the AACE/ACE guidelines as well as others. We look forward to seeing what the leadership decides on the positioning of empagliflozin and liraglutide in the next iteration of the algorithm – it will be very interesting to see where consensus comes out on the committee. While we certainly agree that replicating CV findings in additional studies lend further confidence to the validity of the benefit, we’re not sure how realistic this will be given the extremely high cost of outcomes trials to say nothing of the length of time required – we don’t imagine Novo Nordisk would repeat the LEADER trial, for instance. Additionally, while trials for additional agents in the class can certainly provide more information and confidence in findings if also positive, differences in trial design and participant population – not to mention potential differences in the molecular agent – will certainly make it hard to compare the results apples to apples (there’s lots of differences in the trial designs). We’ve already seen this even amongst the GLP-1 agonist class – the ELIXA trial of lixisenatide, after all, was neutral and it’s unclear if that’s due to the even higher-risk patient population, the relatively short duration of the trial, the short-acting nature of lixisenatide, or the fact that lixisenatide is less homologous to human GLP-1 than liraglutide or semaglutide – or a combination of all three. While we see the logic of a more cautious, “wait-and-see” approach, we have also heard that the inclusion of these data in guidelines is enormously important for busy providers (particularly in primary care) who rely on these guidelines to learn about the unprecedented CV impact of these drugs. We also have begun to think more about patients and their reaction to cardio-protective data. At present, we think far more patients think day to day about the importance of glucose rather than cardiovascular risk – we certainly don’t think most patients are used to thinking about daily or weekly medicines from a cardio-protection perspective. And, yet, CV events prompt some of the highest costs in the system, practically speaking, to say nothing of reductions in quality of life that come from CV events (or dialysis, etc.) We look forward to the field doing more thinking about how to motivate patients in terms of CV risk reduction as this could be a way that some patients begin to feel more motivated (the notion of reducing the risk of a heart attack or stroke).
2. Drs. Ralph DeFronzo and Matthew Weir on Renal Benefit of SGLT-2 Inhibitors
In a deep-dive session on the renal effects of SGLT-2 inhibitors, both Drs. Ralph DeFronzo and Matthew Weir were extremely positive about the renal benefit of these agents and expressed strong confidence that the benefits extend to all members of the class. While acknowledging the mechanistic pathway in which SGLT-2 inhibitors can increase risk of diabetic ketoacidosis (DKA), both thought leaders emphasized that this is a rare and manageable adverse event in type 2 diabetes. As Dr. Weir put it, “The risk is vanishingly small relative to the cardiorenal protection.” Though renal outcomes were only a secondary endpoint in the EMPA-REG OUTCOME CVOT for Lilly/BI’s Jardiace (empagliflozin), both Drs. DeFronzo and Weir were impressed and excited by the data suggesting a renal-protective benefit for the agent. Both speakers acknowledged that the CREDENCE renal outcomes trial for J&J’s Invokana (canagliflozin, expected completion January 2020) will provide more definitive evidence (and potentially support a renal indication), and Dr. DeFronzo passionately stated, “I will drop dead if these drugs don’t give us renal protection.” Indeed, Dr. Weir pointed out that SGLT-2 inhibitors have impressive benefits on blood pressure and albuminuria and “if renal outcomes don’t point in the right direction, it raises questions about everything we’ve learned about RAAS inhibitors in the treatment of diabetic nephropathy.” Further, Dr. Weir suggested that there’s no reason to believe that there are within-class differences between the agents, though he acknowledged that it’s difficult to say with 100% certainty without a head-to-head study, which manufacturers are unlikely to conduct (though presumably we could learn something from big data on this eventually). Overall, Dr. Weir emphasized that the upside to SGLT-2 inhibitors – both from a cardiovascular and a renal standpoint – is “substantial.” Dr. DeFronzo characterized EMPA-REG OUTCOME, along with positive GLP-1 agonist and TZD pioglitazone CVOTs, as heralding a new era of diabetes care in which we are going beyond glucose control to impact CV and renal outcomes. He suggested that it would be great to see outcomes studies of some of these agents in combination, in order to better understand if, say, empagliflozin and liraglutide have additive or synergistic effects on long-term outcomes. We would love to see this as well. Since such a study would likely be quite lengthy and costly, we’re curious if real-world data might be able to shed some light on this topic in lieu of a long-term randomized, controlled trial. The cost of this trial is, of course, extremely low compared to the billions of dollars spent each year on CV and kidney disease in people with diabetes. While a well-designed ambitious outcomes trial would cost in the hundreds of millions, tens of billions are spent annually on these presumably avoidable complications.
3. Dr. Sue KirkMan on Diabetes in Older Adults
Dr. Sue Kirkman discussed the treatment of type 2 diabetes in older adults, ultimately emphasizing her view that the strategy to treat diabetes is more important than the actual A1c target in these patients. She underscored that there is great heterogeneity in the health status of older adults, with a wide range in functional ability and frailty in those 50 and older. What’s more, functional status is only loosely correlated with age and age by itself is not a good predictor of how frail an individual patient is. Thus, it’s important to assess the functional status, cognitive abilities, etc. of these patients and individualize treatment based on this assessment rather than rely on age thresholds to determine therapeutic goals. Like other thought leaders on the treatment of older adults, Dr. Kirkman emphasized the importance of minimizing hypoglycemia risk in this population that is especially vulnerable and acknowledged that the 5-10 year benefits of glycemic control may not be felt by a patient with a less than five year life expectancy. (How a PCP or other doctor would establish whether someone 50 or over would have less than five years’ life expectancy wasn’t established.) On the other hand, while some have advocated for A1c targets up to 9% for older, more frail adults, Dr. Kirkman argued, “Some of this focus on A1c is a bit misguided and it’s more important how we’re lowering A1c.” She expressed dissatisfaction with the American Geriatrics Society Choosing Wisely campaign, which in her view essentially imply that treating to a target A1c<7.5% using any agents besides metformin is bad clinical care. Rather than focus on recommendations for higher A1c targets in older adults, Dr. Kirkman advocated for carefully choosing appropriate medications based on a thorough consideration of their risk/benefit profile as it applies to a particular patient. We applaud this approach and have felt that the focus on “relaxing” A1c guidelines for some older adults can have unintended consequences if busy providers (especially in primary care) interpret them too broadly or too casually. Further, a recent study led by Joslin Clinic’s highly-regarded Drs. Katie Weinger and Medha Munshi showed that higher A1c targets don’t necessarily reduce hypoglycemia rates in older patients, suggesting that the choice of therapy and the use of CGM and other technological tools may be more helpful in reducing hypoglycemia than higher targets in and of itself.
- Dr. Kirkman discussed the pros and cons of all the major diabetes drug classes for the treatment of older adults. She underscored the substantial hypoglycemia concerns associated with sulfonylureas and shared that she tends to avoid their use as much as she can. She was particularly positive about the benign benefit/risk profile of DPP-4 inhibitors – indeed, we feel have learned from many KOLs that the older adult population is particularly suited to this easy-to-take, low-risk oral medication, particularly early in their disease (DPP-4 inhibitors do not have the potency of other classes like GLP-1, SGLT-2s, or insulin). Dr. Kirkman also felt that once-weekly GLP-1 agonists could be a good option for patients requiring greater potency and the ability for a greater impact on higher A1c, especially due to the low risk of hypoglycemia associated with the GLP-1 class. Interestingly, she suggested that the once-weekly formulations could be a good option for patients with cognitive impairments, as a family member could come by once a week to administer the drug. On the other hand, the weight loss effect of GLP-1 agonists (a boon for many patients with type 2 diabetes) may be a concern in some underweight older patients, she said. Dr. Kirkman also touched on the positive evidence for SGLT-2 inhibitors, from low risk of hypoglycemia and weight loss to potential reduction of CV events and death, though she does keep an eye out for hypotension in her older patients on these agents. Despite their overall favorable clinical profiles, Dr. Kirkman lamented the high cost of these newer medications, a particular concern for her patients on Medicare Part D who may be nearing the “donut hole” for coverage. Overall, she emphasized that there is no perfect drug for all older patients and all of these considerations, including cost, must be taken into account when individualizing therapy. We are glad that the medications were developed and point out the broad societal benefits that Big Pharma is enabling longer-term when these drugs can be made available to tens of millions more patients when they are in generic form.
- Dr. Kirkman suggested that, while she likes the clinical profile of DPP-4 inhibitors, their cost must be weighed against their impact on glycemic control and hypoglycemia. She pointed to Dr. Kasia Lipska’s findings that increased usage of newer diabetes drugs and decreased usage of SUs between 2006 and 2013 did not improve glycemic control or reduce hypoglycemia rates in the overall population. Dr. Lipska’s paper certainly lends itself to broad brush conclusions in the mainstream media that “newer diabetes drugs aren’t worth the money” – importantly though, Dr. Kirkman was not making this point herself and was largely pointing out that cost is an important consideration when weighting the benefits (or lack thereof) of a therapy against its downsides. That said, we’ve written extensively about this paper and we think it’s extremely important for those who write or speak about this paper to present a more nuanced view of its implications. First, while DPP-4 inhibitor and GLP-1 agonist usage significantly increased and SU usage decreased in the study population, the usage of SUs in 2013 (31%, down from 39% in 2006) still eclipsed that of the other two classes (15% usage of DPP-4 inhibitors in 2013, up from 0.5% and 5% usage of GLP-1 agonists, up from 3%). Furthermore, none of the patients in this paper were on SGLT-2 inhibitors – and overall usage of “new drugs” was only 20% at the end of the study period. Additionally, this study looked at the general population of people with type 2 diabetes, not just older adults who are at higher risk of hypoglycemia, so it’s possible that the relatively low rate of hypoglycemia in the general type 2 diabetes population masked the benefits of newer therapies in those more vulnerable to hypoglycemia, such as older adults. Overall, in our view, it would take much greater usage of DPP-4 inhibitors, GLP-1 agonists, and SGLT-2 inhibitors to sway hypoglycemia rates at the population level. We would have loved to see several subgroup analyses of this data: How did glycemic control and hypoglycemia rates change in older adults specifically? What were hypoglycemia rates specifically for those starting DPP-4 inhibitors and GLP-1 agonists during this time period? Since the publication of this study, we’ve been concerned about the broad brush takeaways and headlines these findings and the study authors’ (in our view, misguided) conclusions about the cost-effectiveness of new diabetes drugs can prompt. Indeed, this is the second time in a month that we’ve heard a high-profile leader in the diabetes field cite Dr. Lipska’s data – Dr. David Nathan also pointed to this data in his highly controversial debate with Dr. Daniel Drucker at ENDO 2017. That said, Dr. Kirkman’s citation of Dr. Lipska’s paper was a relatively small part of her overall wide-ranging and thoughtful discussion of diabetes treatment in older adults and she emphasized to us that she was in no way advocating for the use of all older drugs or suggesting that newer drugs are uniformly not cost-effective. We appreciated Dr. Kirkman’s clarification and hope that other leaders cite Dr. Lipska’s work with similar care and thoughtfulness; we also hope that Dr. Lipska will take on the requested sub-group analysis to see how hypoglcyemia in GLP-1 and DPP-4 inhibitors compared to hypoglycemia in SFUs, as that’s the real question, not just how hypoglcyemia changed wholesale in a population over the long-term.
4. All About Bones with Dr. Clifford Rosen
Dr. Clifford Rosen (Maine Medical Center Research Institute, Scarborough, ME) discussed the impact of different diabetes drug classes on bone in a comprehensive overview of the research connecting type 1 and type 2 diabetes to bone fracture risk,. He suggested that DPP-4 inhibitors may improve fracture healing, since the enzyme DPP-4 slows down bone formation. In rodent models, osteoblasts (the cells that secrete the matrix for bone formation) recruit DPP-4 inhibitors, and when administered a drug from this class, mice show better osteoblast number. Dr. Rosen established early on in his talk that people with diabetes experience greater difficulty healing post-fracture, and he thus positioned DPP-4 inhibitors as “worthy of significant clinical attention” to address this complication. In our view, this evidence further reinforces the position of DPP-4 inhibitors as an ideal choice for older patients (many of whom are vulnerable to elevated fracture risk) based on their benign safety/tolerability profile. On the other hand, Dr. Rosen presented insulin as most likely having neutral effects on the skeleton, while he emphasized that insulin-sensitizers like TZDs require more evaluation. TZDs have long been associated with heightened fracture risk, but important differences have surfaced in recent years distinguishing rosiglitazone from pioglitazone. Given the CV benefits linked to low-dose pioglitazone in the IRIS trial (on top of the drug’s generic status/low cost), many thought leaders have been returning to this agent for diabetes care – we were encouraged to hear a similar beat from Dr. Rosen, though he cautioned that more research might perhaps confirm the bone-related safety risks that have previously been identified for this therapy class.
- Dr. Rosen refrained from sharing any specific details on SGLT-2 inhibitor Invokana (canagliflozin) and its association with bone fractures – “I can’t tell you about it. You’ll have to wait until CANVAS presents at ADA.” He underscored that fractures are not a class effect in this case. Back in September 2015, the FDA strengthened the label warning for bone fracture risk associated with J&J’s Invokana, but neither AZ’s Farxiga (dapagliflozin) nor Lilly/BI’s Jardiance (empagliflozin) have such label warnings. From our perspective, it seems like this safety warning (alongside concerns over DKA, lower limb amputation, and acute kidney injury) has negatively impacted J&J’s SGLT-2 inhibitor business – Invokana has been losing market share to Jardiance in the wake of positive EMPA-REG OUTCOME results, while Farxiga has mostly maintained its share of the market by value and by volume. All should do well commercially since this class is growing, though it is difficult to EMPA-REG OUTCOME found no significant difference in the incidence of bone fractures between participants treated with various doses of empagliflozin vs. placebo. Canagliflozin may tell the same or a different story, and we’ll have to wait until ADA 2017 in San Diego for the full CANVAS results to weigh in on this safety story. We’re itching for this data, not only because we’re hoping for more evidence in support of a cardioprotective class effect, but because any reassuring safety results on Invokana would likely boost the whole SGLT-2 inhibitor market – these agents show profound glucose-lowering and weight loss efficacy, and we’d love for more patients to benefit from them, provided they are safe and tolerable.
5. American Health Care Act (AHCA) and Trump Presidency: What’s Next?
Less than 24 hours after the US House of Representatives passage of the American Health Care Act (AHCA), Ms. Jill Rathbun, a managing partner at Galileo Consulting Group, offered her take on what the next few months of the Trump Presidency might mean for healthcare. Overall, she framed the Trump Administration’s healthcare efforts with one concept: Less. “This administration is really about ‘less,’” as she put it, “Sometimes less is more and sometimes less is just less.” While there are cases of the former in the Trump Administration’s efforts (such as reducing the burden of EHR reporting for providers), the AHCA is unquestionably a case of the latter, in which patients will very likely have less insurance coverage. Ms. Rathbun emphasized the importance of understanding the proposed law and its potential impact, so that providers and the rest of the diabetes and healthcare community can effectively advocate for changes. She emphasized that the current proposed law is likely to undergo significant change, and it’s crucial that those in the healthcare field are ready to provide specific policy advice during this process that will hopefully minimize the negative impact to patients. Overall, Ms. Rathbun concluded, “Their less is more – more room for our ideas, and we need to be prepared to offer them.” Given the enormous complexity of healthcare in the US, we greatly appreciated Ms. Rathbun’s detailed discussion of the implications of the AHCA and echo her thoughts on the crucial importance of patient and provider advocacy during this process. Within the diabetes field, we were pleased to see the ADA, JDRF, and the Endocrine Society take a stand against this bill on behalf of people living with diabetes and those who care for them.
- Ms. Rathbun provided an overview of the litany of changes in the law that will very likely translate into reduced health coverage overall, including repeal of ACA health coverage mandates, removal of actuarial standards for health plans that required a certain percentage of premiums to go toward health benefits (rather than marketing, etc. for insurers), and elimination of subsidies to purchase health coverage and pay for deductibles/copays. Instead, the AHCA will offer tax credits to replace the premium and cost-sharing subsidies – these tax credits will be based on age, which led Ms. Rathbun to worry that the low level of financial help in purchasing coverage will lead too many healthy young people to opt-out of the insurance market, which would drive up the cost of insurance and make it possible that even the max $4,000 credit would not be enough to cover the costs of health coverage for older and more sick adults. The responsibility for these older and more sick individuals would also largely shift to the states – the AHCA would create a “stability fund” of ~$138 billion (an additional $8 billion from the previous iteration of the AHCA, included to woo moderate Republicans) for states to help cover deductibles and premium costs for people with pre-existing conditions in a “high-risk pool.” That doesn’t sound good to us to have more variability introduced, though the devil will be in the details. That said, Ms. Rathbun noted that estimates have suggested that even this large pool of money will not be enough to adequately meet the needs to Americans currently living with pre-existing conditions – in fact, she pointed to estimates suggesting that this number is about $60 billion short of what’s needed. On top of all of these nationwide changes, the AHCA also offers individual states to waive the requirement of coverage for essential benefits, allow consideration of pre-existing conditions in determining plan cost in some circumstances, and remove age-banding, in which the cost of premiums for older members compared to younger members is capped.
- Despite the bleak outlook on healthcare as the AHCA is written, Ms. Rathbun offered some hope by emphasizing the long road and challenges the bill must navigate before it is signed into law. She suggested that the proposed law could change substantially in the Senate and it’s important to remember that this debate could go on until as late as December. First in the process moving forward, the Congressional Budget Office (CBO) must score the bill before it can pass forward to the Senate (in a rare move, the House had voted on the bill ahead of CBO scoring). Next, since the bill is being passed under the Reconciliation Process (in order to avoid a filibuster to potentially block an eventual vote on the bill), it is subject to a complex set of rules (including the “Byrd Rule”) which could force substantial changes in the bill, including to the major changes in the second version of the AHCA that swayed the more conservative members of the House to vote for it. Finally, Ms. Rathbun pointed out that Republican majority in the Senate is much more tenuous – the Republicans can only afford to lose two votes and still pass the bill and Ms. Rathbun estimates that they’re already eight to ten votes down with the current version of the bill.
Top Obesity Highlights
1. ACTION Study Sub-Group Analysis Uncovers Unique Factors Influencing Weight Management in Older Americans with Obesity
In a poster, a sub-analysis of people over 65 in the Novo Nordisk-sponsored ACTION study described the experience of obesity in older Americans: they are diagnosed with obesity less frequently despite having more complications, and seek less support from physicians and yet succeed at weight loss more often. These findings were also shared in a press release from the company. Novo Nordisk’s ACTION study made waves at Obesity Week 2016 as the first ever large-scale investigation exploring the factors underlying the barriers to weigh management from the differing perspectives of stakeholders ranging from healthcare professionals (n=606), employers (n=153), and, most crucially, people with obesity themselves (n=3,008). Although older people with obesity (who comprised 31% of the people with obesity enrolled in the ACTION study) report considering obesity a disease at a similar frequency as their younger counterparts (66% vs. 64%), this group showed important differences in how they perceive and manage their obesity. Perhaps most crucially, though unsurprisingly, older people with obesity report greater comorbidity prevalence than younger people with obesity – 73% have high blood pressure (versus 43% for those under 65), 62% have high cholesterol (versus 34%), 31% have sleep apnea (versus 22%), and 31% have type 2 diabetes (versus 18%). Despite these trends suggestive of greater disease severity in older people, fewer older people with obesity (50%) report having received a formal obesity diagnosis than their younger counterparts (56%; p<0.05). That said, a greater number of older people with obesity reported weight loss success (defined as at least 10% body weight loss) in the past year compared to younger counterparts (13% versus 9%, p<0.05) even though a greater proportion of older people with obesity reported that they “do not seek support” from their physician for weight loss (44% vs. 35%, p<0.05). These counterintuitive findings can perhaps be explained by different motivations for obesity management among older versus younger people: a greater proportion of older people with obesity reported that a specific medical event (heart attack, stroke, etc.) had a profound influence on their desire to manage weight (16% vs 12%, p<0.05) and cited improving existing health conditions as an overall goal to achieve as part of weight management (67% vs. 62%, p<0.05). This sub-analysis has immediate implications for obesity clinical practice. According to the study authors, clinicians should be especially attentive to the barriers and challenges toward obesity management in older people. Furthermore, given that previous health events are especially motivating forces for weight loss in older people, clinicians should change the conversation so that patients receive counseling about weight management before and not after such an event takes place. This study reinforces that older patients have significantly different motivations and concerns from younger patients, and these considerations are important to keep in mind when individualizing therapy for older adults.
2. ABCD: A New Name for Obesity
Dr. Timothy Garvey (University of Alabama, Birmingham, AL) highlighted the recent AACE position statement on obesity, which proposes a new name for the medical condition – adiposity-based chronic disease (ABCD). The suggested term is fitting, although we’re not sure patients (or some doctors) would be able to rattle off what it stands for: that said, obesity is indeed a chronic disease that requires lifelong management, is associated with complications that confer morbidity and mortality, and aligns with the classic primary, secondary, and tertiary prevention phases of a chronic condition. Dr. Garvey argued that “obesity” was severely lacking as a label because it’s not actionable, it’s not informative for overall health and wellness, nor is it sufficiently specific. “Obesity” doesn’t tell you anything about adipose tissue mass or the long-term complications an individual patient will encounter. The term is also clouded with stigma by now, and research shows that even well-trained healthcare providers display an unconscious bias toward patients with high BMI. Transitioning language in this therapeutic area to talk about “adiposity-based chronic disease” could circumvent this stigma and bias. Dr. Garvey explained that ABCD medicalizes the condition and encourages people to think about it in the same category as any other disease, with symptoms and adverse health effects. Indeed, promoting the concept of obesity as a biological disease is a crucial first step in promoting great acceptance of chronic medical management of obesity among patients, providers, and payers. Uptake of obesity drugs, for example, remains low despite the demonstrated safety and efficacy of some of these newer agents (especially Novo Nordisk’s Saxenda) – providers/patients may be more likely to consider Saxenda as a therapy for adiposity-based chronic disease vs. obesity, and payers may be more likely to reimburse the drug for ABCD as well. We’re thrilled to see AACE stepping up with clear obesity treatment guidelines as well as this effort to medicalize the term. We see great potential for ABCD to combat stigma and unconscious provider bias, which is an absolutely essential goal, given that the vast majority of people with obesity aren’t currently receiving any medical treatment. AACE has been a trailblazer in the obesity healthcare field for some time now – the organization was one of the first to recognize obesity as a disease in 2011 (preceding even the American Medical Association’s recognition by two years) and to create complications-based treatment guidelines for the condition in 2016. We’re glad to see their continued leadership in this field!
3. Dr. Lee Kaplan’s Core Principles of Obesity Treatment
In a very actionable talk, the always-engaging Dr. Lee Kaplan (Harvard Medical School and Massachusetts General Hospital, Boston, MA) presented an overview of his core principles for obesity treatment. He began by defending the stance that the physiological regulation of energy balance drives eating behavior (and not the other way around), and that the body has a set point weight that it vigorously defends, making weight loss far more complicated than a simple equation of calories consumed and calories burned. Against this backdrop, Dr. Kaplan pointed out that we live in an environment that creates the “perfect storm” for abnormal metabolic physiology – from unhealthy dietary constituents, low muscle mass, sleep deprivation, disrupted circadian rhythmicity, and high prevalence of weight gain-inducing medications. Lifestyle interventions should focus on counteracting these forces with healthy diet, regular physical activity, more and better sleep, stress reduction, and stable eating patterns, he argued, and if this isn’t effective, anti-obesity medications followed by bariatric surgery can provide an extra push (though it is difficult to predict who will respond best to which therapy). Of course, the dream is to be able to replicate the effects of bariatric surgery via less invasive endoscopic or next-generation pharmaceutical techniques, and Dr. Kaplan expressed optimism that further research into the mechanism of action behind the metabolic effects of bariatric surgery can help make this a reality. Above all, Dr. Kaplan advised physicians to “treat obesity as you would treat any other disease” by approaching patients in a supportive and non-judgmental way, matching therapeutic invasiveness to obesity severity, and using combination therapies when possible to enhance benefit and minimize risk. Though obesity rates are rising at an epidemic level, this increasingly prevalent disease continues to be an area of unmet need. we appreciate Dr. Kaplan’s cogent advice in a challenging disease state that continues to be so misunderstood.
4. “Culinary Medicine” in the Treatment of obesity
In a highly-entertaining talk, Dr. Tim Harlan (Tulane University, New Orleans, LA), a chef and restaurateur-turned-physician, provided a fascinating overview of his “culinary medicine” approach to obesity. He compellingly posited that traditional medicine sets people with obesity up for failure with its overemphasis on the number of pounds lost and argued that physicians should focus more on the “other half of the equation – the quality of the calories we put in our mouths.” To this end, he recently established the Goldring Center for Culinary Medicine, a first-of-its kind teaching kitchen owned and operated by Tulane University that, in addition to educating the community about health eating via free family cooking classes, educates medical students on how to teach their patients about nutrition. Dr. Harlan’s curriculum focuses on the Mediterranean diet given its extensively researched status, but he was careful to emphasize that “it’s not about recipes” and the principles of the Mediterranean diet can be applied to any cuisine by simply promoting nine key points: vegetables, legumes, fruits, nuts, whole grains, fish, monounsaturated fat, alcohol in moderation, and red meat in moderation. Literature suggests that improving one’s Mediterranean diet score by as little as two of these points has a marked impact on all-cause mortality – and, Dr. Harlan pointed out, it’s free. For this reason, he advised physicians to make use of this short, simple message of “two points” and begin the conversation about nutrition by asking patients for a diet recall (in which patients list everything they have eaten in the last 24 hours) – he emphasized that asking about this is just as important as asking about family medical history and surgical history. A testament to the program's success, Dr. Harlan shared that, to date, the Goldring Center's nutritional medicine curriculum is now being taught at over 30 medical and nursing schools.
--by Abigail Dove, Helen Gao, Brian Levine, Payal Marathe, Adam Brown, and Kelly Close