ADA publishes 2019 Standards of Care; New diabetes technology section included – December 17, 2018

Executive Highlights

  • On Monday, the ADA published its Standards of Medical Care in Diabetes for 2019, (198 pages, 1,730 citations). Overall, it is an upgrade from the 2018 document to have a full section on tech, with a smattering of oddities. We were encouraged to see strong CGM recommendations for adults with type 1 diabetes (including during pregnancy! This is such a win from an awareness perspective alone) – an “A” grade for evidence to reduce A1c in those not at target. There was a slightly more conservative read on pediatric CGM use, which received a “B” grade and modest phrasing (“should be considered”) – we felt “expert opinion” should’ve easier taken that up to an A. FreeStyle Libre is oddly a separate section, with “C” evidence for replacing fingersticks – that was slightly surprising since it has sailed through FDA.

  • There was no broad recommendation on use of CGM in type 2 – even for intensive insulin users or professional (diagnostic) CGM although those on intensive insulin are shown in Section 7.6 that CGM should be considered. It was positive to see a whole automated insulin delivery section, though it offered a fairly limited review of the evidence (focused on 670G) and lacked any mention of Tandem’s Basal-IQ (predictive low glucose suspend). Still, the “B” recommendation for hybrid closed loop is a noteworthy upgrade from last year’s more limited recommendation for adolescents only. Finally, there is a strong “A” recommendation for the use of sensor-augmented pump therapy in children, adolescents, and adults with type 1 diabetes, with an oddly weaker “C” recommendation for pump therapy alone. Smart pens are mentioned, but without evidence grading yet – that seems fine and one of many great things about the Standards these days is that they are reviewed often and can be easily changed or adapted.

  • Personalized care is the key thematic focus of these Standards, reflected in the ADA’s headline on the updated document. Calling for a “paradigm shift” toward patient-centered diabetes care, the ADA made a number of refinements across demographics and other personal factors: We noted stronger recommendations on NAFLD/NASH evaluation, an expanded and more specific section on language in diabetes, and more personalized (though still a bit general) nutrition guidance – the latter is particularly needed and we are very excited about new new nutritional guidelines that are scheduled to be released in 2019 that emphasizes individualized nutritional guidance. Notably, new algorithms were created to guide HCPs in (i) simplification of insulin therapy among older adults for whom de-intensification is appropriate; and (ii) treating new-onset type 2 diabetes in overweight youth, an increasingly important issue. We believe some caution is in order over the “simplification of therapy” – rather than creating higher A1c targets, we hope that different therapy will be offered that helps patients manage glucose as well as possible while reducing risk of hypoglcyemia and enabling weight loss and cardioprotection.  

  • The treatment algorithm and therapy recommendations were updated to align fully with the recent ADA-EASD Consensus Report. Most notably, GLP-1s are now recommended as the first-line injectable over basal insulin, and GLP-1s and SGLT-2s are recommended for those with predominant ASCVD (either class) or HF/CKD (SGLT-2s preferred). Unfortunately, results on dapagliflozin from DECLARE have not been incorporated yet; we have confirmed with the ADA the results are currently under review by the PPC for a living Standards of Care update in early 2019.

  • Compared to previous versions, though, CV disease is very prominently featured in the treatment decision cascade, and the CVD management chapter is endorsed by the ACC. These Standards also feature a new flow chart on injectable therapy intensification, plus, notably, a table on hypoglycemia risk assessment.

  • We were disappointed to see the section on noninsulin treatment for type 1 – already quite small – was cut nearly in half, a confusing decision given the use of adjunct therapies is only becoming more common. We were informed by ADA that it recognizes the unmet need for additional and adjunctive therapies for individuals with Type 1 diabetes. As the Standards reports on approved indications, the abbreviated section should not be interpreted as this area not being important. As new evidence is obtained and when moving toward an indication, this clearly will be updated.

On Monday, the ADA published its official Standards of Medical Care in Diabetes for 2019 in Diabetes Care. Here, we review and contextualize the most notable updates compared to the 2018 Standards of Care, broken down by topic. As a reminder, the Standards became a living document with the 2018 edition, and those updates are posted here. See the ADA’s announcement.

Diabetes Technology

Strong stance on CGM in adults includes recommendation for use in pregnant women; continued conservative view for use in pediatrics; FreeStyle Libre its own “isCGM” section

  • “When used properly, real-time continuous glucose monitoring in conjunction with intensive insulin regimens is a useful tool to lower A1C in adults with type 1 diabetes who are not meeting glycemic targets. A

    • We’re glad to see the same strongly scored recommendation for CGM use in adults repeated from last year’s guidance. However, as we pointed out last year, the language could be misconstrued to suggest that CGM does not also provide benefit to those at their glycemic targets hoping to maintain a low A1c without hypoglycemia.  However, in the new technology section are the new parameters that appear on CGM reports that reflect new parameters such as Time in Range.

    • Promisingly, the recommendation: “real-time continuous glucose monitoring may be a useful tool in those with hypoglycemia unawareness and/or frequent hypoglycemic episodes” is now considered to have B-level evidence – a significant step up from the C grade awarded in last year’s guidance. Still, the landmark HypoDE trial, which showed CGM to significantly reduce hypoglycemia incidence in MDI users with type 1 diabetes and impaired hypoglycemia awareness, was notably absent from the section on CGM’s impact on hypoglycemia.  We were informed by ADA that the technology chapter will continue to expand as this was a new section this year. So, new data in this regard can be expected.

  • “Real-time continuous glucose monitoring may be used effectively to improve A1C levels and neonatal outcomes in pregnant women with type 1 diabetes. B

    • Given that there are few studies examining the use of CGM during pregnancy, it was outstanding to see this recommendation scored with B-level evidence. As the guidance authors noted, CONCEPTT was particularly “well-designed,” showing positive neonatal outcomes – and with Medtronic’s very old Guardian CGM to boot! We hope to see this body of evidence expand in 2019 to include studies with more recent CGMs, which we think may have a greater impact on maternal outcomes as well. Dexcom has up to three studies planned for gestational diabetes in 2019.

    • We found it odd that there was no official statement on use of CGM in type 2. While several studies of CGM in people with type 2 diabetes were cited, including DiaMonD in type 2, the ADA only provided specific recommendations for those with type 1 diabetes. This is a bit of a step back from last year’s document, which included the following statement: “Continuous glucose monitoring (CGM) also has an important role in assessing the effectiveness and safety of treatment in subgroups of patients with type 1 diabetes and in selected patients with type 2 diabetes.” Instead, there was the following broad-strokes recommendation: “Most patients using intensive insulin regimens (multiple daily injections or insulin pump therapy) should assess glucose levels using self-monitoring of blood glucose (or continuous glucose monitoring) prior to meals and snacks, at bedtime, occasionally postprandially, prior to exercise, when they suspect low blood glucose, after treating low blood glucose until they are normoglycemic, and prior to critical tasks such as driving. Overall, we believe that some will see this as greater enthusiasm and again, we’d love to see “expert opinion” used more. B”

  • Real-time continuous glucose monitoring should be considered in children and adolescents with type 1 diabetes, whether using multiple daily injections or continuous subcutaneous insulin infusion, as an additional tool to help improve glucose control and reduce the risk of hypoglycemia. Benefits of continuous glucose monitoring correlate with adherence to ongoing use of the device. B

    • The ADA’s recommendation regarding CGM use in children and adolescents has remained unchanged since the 2018 guidelines. While we recognize there are fewer CGM studies in pediatrics than in adults, we would hope to see this recommendation rise to A-level evidence or to switch from “should be considered” to “is standard of care in all patients with type 1 diabetes.”

  • Intermittently scanned continuous glucose monitor use may be considered as a substitute for self-monitoring of blood glucose in adults with diabetes requiring frequent glucose testing. C

    •  FreeStyle Libre was given its own category distinct from CGM – intermittently scanned CGM (isCGM). The FreeStyle Libre section was actually longer than the automated insulin delivery section and included the only mention of factory calibration, despite the Dexcom G6 also requiring zero fingersticks. FreeStyle Libre was described as “smaller than those of other systems and is water resistant,” diving into greater product detail than in the general CGM section – e.g., the latter doesn’t even (yet) mention that a 90-day implantable sensor exists and incorrectly refers to “adjunctive use” when describing devices approved by the FDA to make treatment decisions without SMBG confirmation (the correct term is “non-adjunctive use”).

  • Despite citing the international consensus paper on CGM, the authors incorrectly defined hyperglycemia as ≥180 mg/dl as opposed to the accepted >180 mg/dl (time-in-range was correctly defines as 70-180 mg/dl). We have been notified by the ADA that this will be corrected in the online version. We were pleased to see the authors reference the renaming of eA1c to glucose management indicator (GMI) and to see an emphasis on standardized reports such as the AGP.

Moderate strengthening of automated insulin delivery recommendations to include adults; Basal-IQ not mentioned

  • “Automated insulin delivery systems may be considered in children (>7 years) and adults with type 1 diabetes to improve glycemic control. B

    • Given that last year’s document included a statement on the use of automated insulin delivery systems in adolescents only, we’re pleased to see a broader recommendation for children and adults with type 1 diabetes, albeit graded with B-level evidence. We were surprised to see no mention of Tandem’s t:slim x2 with Basal-IQ (predictive low glucose suspend) and Dexcom G6 integration, as we consider this system automated insulin delivery – even if it’s not a hybrid closed loop. The guidance, however, defines AID as comprised of an insulin pump, CGM, and an algorithm allowing insulin delivery to not “only be suspended but also increased or decreased based on sensor glucose values.”

    • Last year, the guidance surrounding AID included the following, which was notably absent in this year’s statement: “The safety of hybrid closed-loop systems has been supported in the literature and may have advantages over sensor-augmented pump therapy in specific populations, such as pregnant women with type 1 diabetes.” While this year’s recommendations included a study published in The Lancet, which showed that the Medtronic 640G reduced the risk for hypoglycemia and improved A1c as compared to sensor-augmented pump therapy, there was no broader statement similar to the above.

  • We were interested to see brief mention of DIY closed loop systems. Although the authors provided very little context apart from noting these systems are not FDA approved or recommended, at least the DIY community was mentioned.

Strong statement in favor of sensor-augmented pump therapy; weaker for pump therapy alone

  • “Insulin pump therapy may be considered as an option for all children and adolescents, especially in children under seven years of age. C

    • We were surprised to see such a conservative recommendation for pump therapy in children and adolescents, not to mention the lack of any recommendation for adults. Still, this is an improvement over last year’s recommendations, which did not include any pump-specific commentary that we could find.

    • Later in the document, the authors emphasize that “pump therapy may be the preferred mode of insulin delivery for children under seven years of age.” The authors note a dearth of data in adolescents and youth with type 2 diabetes as preventing recommendations for this age group.

  • “Sensor-augmented pump therapy may be considered for children, adolescents, and adults to improve glycemic control without an increase in hypoglycemia or severe hypoglycemia. Benefits correlate with adherence to ongoing use of the device. A

    • Given the weak stance in the insulin pump section, we were glad to see such a strong statement in favor of sensor-augmented pump therapy under the CGM section. We’re not quite sure why pump therapy in children and adolescents is only graded a C, whereas sensor-augmented pump therapy for children, adolescents, and adults is graded an A. Perhaps the authors believe that the benefits of pump therapy are only conferred when enhanced with CGM. Alternatively, it could simply be a matter of insufficient evidence, as the authors claim that “most studies” comparing MDI with pump therapy have been “relatively small and of short duration.” Still, the authors do note a systematic review and meta-analysis published in 2012, which found pump therapy to confer “modest advantages” for lowering A1c and for reducing severe hypoglycemia in children and adults.

  • “Pump therapy can be successfully started at the time of diagnosis. Practical aspects of pump therapy initiation include: assessment of patient and family readiness, (although there is no consensus on which factors to consider in adults or pediatrics), selection of pump type and initial pump settings, patient/family education of potential pump complications (e.g., diabetic ketoacidosis [DKA] with infusion set failure), transition from MDI, and introduction of advanced pump settings (e.g., temporary basal rates, extended/square/dual wave bolus).”

    • We were pleased to see mention of initiating pump therapy immediately following diagnosis. The authors did identify a noteworthy gap in helping providers choose which type of insulin administration is best for an individual patient. While endocrinologists may feel comfortable making this call, it is likely to be meaningfully more challenging for a primary care provider. Developing some sort of decision-making guide could be helpful here, especially as many continue to push for CGM-first and then pumps to be added later. The ADA informed us this issue is being considered by the PPC.

  • Given the additional barriers to optimal diabetes care observed in disadvantaged groups, addressing the differences in access to insulin pumps and other diabetes technology may contribute to fewer health disparities.”

    • The authors raised the crucial point that adoption of pump therapy in the US shows marked geographic variation, which may be related to “provider preference or center characteristics and socioeconomic status.” We salute ADA for noting the potential for diabetes technology to widen health disparities in the US.

  • “For people with diabetes who require insulin, insulin syringes or insulin pens may be used for insulin delivery with consideration of patient preference, insulin type and dosing regimen, cost, and self-management capabilities. B

    • While this statement is rather general, we were encouraged by the section on insulin syringes and pens as a whole. The section referenced smart pens “that can be programmed to calculate insulin doses and provide downloadable data,” as well as those that “include a memory function…[to] recall dose amounts and timing.” Given that Companion Medical’s InPen is the only currently commercially available smart pen in the US, we were glad to see connected pens on ADA’s radar, as several are coming down the pipeline in the next one-to-two years, including Novo Nordisk’s connected NovoPen 6 and Echo Plus, slated to launch in early 2019. See our smart insulin pen and cap competitive landscape.

  • We were also pleased to see the authors reference a “disposable patch-like device” as “another insulin delivery option,” no doubt meaning Valeritas’s V-Go. While they did not mention use in patients with type 2 diabetes specifically, V-Go is most commonly used by those with type 2 diabetes.   

Diabetes Therapy

Patient-Centered Care Takes Center Stage

  • In line with the ADA/EASD Consensus Report calling for “a paradigm shift” to more patient-centered type 2 diabetes care, the 2019 Standards of Care seek to integrate system- and patient-level approaches to improve health across populations while recognizing that diabetes care must also be individualized. To this end, the document drives home the importance of patient-centered care, defined as “care that is respectful of and responsive to individual patient preferences, needs, and values and that ensures that patient values guide all clinical decisions” through multiple recommendations across demographics, nutrition, language, and treatment algorithms. Most illustrative of ADA’s commitment to patient-centered care, the Standards now incorporate the ADA/EASD diabetes care decision cycle to emphasize the need for ongoing assessment and shared decision making to achieve goals and avoid clinical inertia (see below). Leaning into this paradigm, the Standards recommend for the first time that diabetes should be managed by a multidisciplinary team that may draw from PCPs, specialists, nurse practitioners, physician assistants, nurses, dietitians, exercise specialists, pharmacists, dentists, podiatrists, and mental health professionals. While this sort of holistic care is, unfortunately, not yet possible for all patients and health systems, we are nonetheless glad to see the importance of a care team explicitly and aspirationally called out, recognizing the breadth of the impact diabetes can have on daily life and a person’s health.


  • In accordance with increasing recognition of the overlap between NAFLD/NASH and type 2 diabetes, ADA now recommends that patients with type 2 diabetes or prediabetes and either elevated liver enzymes or fatty liver on ultrasound should be evaluated for NASH and liver fibrosis. We imagine that this recommendation could go a long way in terms of patient and provider awareness of the condition – one of three key challenges to the successful commercialization of drugs for NASH, according to Dr. Amama Sadiq at the 2018 NASH Summit. To this end, the implications of greater inclusion of NASH in the Standards of Care could be manifold for greater disease awareness and subsequent uptake and commercial success of NASH drugs once they reach the market.


  • Slightly updated recommendations on person-centered and strength-based language were added following the incorporation of the language movement into the 2018 Standards of Care. At the time, this addition wasn’t particularly surprising considering the late 2017 paper in Diabetes Care (from ADA/AADE), addressing word choice and outlining language recommendations. New text in the 2019 Standards exacts the five recommendations from the 2017 paper to use language that: (i) is neutral, nonjudgmental, and based on facts, actions, or physiology/biology; (ii) is free from stigma; (iii) is strength based, respectful, and inclusive that imparts hope; (iv) fosters collaboration between patients and providers; and (v) is person-centered (e.g., “person with diabetes” is preferred over “diabetic”). We were thrilled to see a few more lines dedicated to this important topic and that a more explicit description of “person-centered, strength-based language” was included – two improvements we called for in our evaluation of the 2018 Standards of Care report. Doubtless, language is a critical component of psychosocial care for people with diabetes, and these issues are being increasingly emphasized in the field.


  • In short, ADA’s nutrition recommendations maintain that that there is no “one-size-fits-all” eating pattern for people with diabetes. With this in mind, several specific considerations were added regarding low-carb diets – specifically that those who are pregnant, children, and people with renal disease or disordered eating behavior should avoid these meal plans. Moreover, low-carb diets should be used with caution among those taking SGLT-2 inhibitors, due to a potentially increased risk of DKA. On prevention, ADA slightly bolstered its support of the importance of weight loss in nutritional interventions for those who have overweight or obesity and are at risk of developing type 2 diabetes, advocating that people being treated with weight loss therapy should have access to ongoing support and additional therapeutic options such as pharmacotherapy if needed. As stated above, more comprehensive nutritional information will be coming in 2019 with the ADA’s updated nutritional consensus statement.

  • Emphasis was placed on the increased risk of type 2 diabetes with tobacco use, as well as smoking cessation. Specifically, a new section notes that the years immediately following smoking cessation may confer increased risk for diabetes that should be monitored. Moreover, the previous discussion on e-cigarettes was expanded, explaining the lack of rigorous evidence that e-cigarettes can facilitate smoking cessation better than “usual care” (access to educational materials and other cessation strategies such as a text-messaging service with encouragement/advice/tips).

Care in Older and Younger Populations

  • A few additions emphasize individualization of glycemic targets and treatment deintensification in older adults. The section on glycemic targets contains a new recommendation to reevaluate the validity of glycemic targets over time, recognizing that the risks and benefits of a certain target may change as diabetes progresses and patients age. Additionally, the section on older adults gained a new figure and table (figure 12.1, below, and table 12.2) offering guidance on simplification of insulin regimens and considerations when deintensifying treatment/deprescribing medications in older adults. The table details different levels of patient health (healthy to very complex/poor health or end of life) with reasonable A1c goals (ranging from <7.5% to <8.5%), providing guidance on when regimen simplification or treatment deintensification/deprescribing may be required (often in response to hypoglycemia or based on patient preference).

  • Another new algorithm (see below, Figure 13.1) on the management of new-onset diabetes in youth was added as well. There are few surprises here, and we note that ADA meaningfully expanded this section in 2018 also. Given the emergence, most notably through RISE, of highly concerning data on both the prevalence and pathophysiology of type 2 diabetes in youth, we’re glad to see ADA make a strong effort to promote and clarify the most evidence-based treatment for this set of highly vulnerable patients.

Treatment Algorithm (Figure 9.1): Alignment with ADA/EASD

  • Pharmacotherapy recommendations have been aligned with the ADA-EASD Consensus Report, as reflected in substantially revised figures taken from the Consensus (below). Baseline ASCVD takes a more prominent position than in the past (compared to figure 8.1 in the 2018 Standards) as the first branch point in treatment selection, and the incorporation of CKD into this consideration is also a large step forward – see the next section for a deeper dive into this part of the algorithm. When it comes to patients without baseline ASCVD or CKD – who comprise the majority of patients with diabetes – the algorithm then moves to other considerations, including hypoglycemia, weight, and cost. Some have posited the criticism that these three factors are important for every patient: Who isn’t concerned about hypoglycemia, weight gain, or cost of medications? The ADA informed us that the algorithm selection is designed to list all factors. It is intended to be guided by predominant patient consideration, and all factors need to be discussed before treatment decisions are made. That said, we do think there are key advantages to this process: In past years, algorithms have told the HCP when treatment should be intensified and then left the provider to comb through a large table of drug classes and their characteristics to be matched to the patient. While those tables still exist in the 2019 Standards (as they should!), this algorithm makes more direct suggestions as to which classes fill which key patient criteria. To be sure, it’s unfortunate to see SUs so prominently recommended for cost concerns – though we can’t deny their affordability – but we can also imagine this figure helping HCPs intensify therapy more easily.. To this point, said Dr. Will Cefalu: “Our standards are read and used throughout the world, and need to be applicable. Not all patients will have access to the newest medications in the US or in other places in the world.” Nevertheless, we understand that these standards are read and used throughout the world and must be applicable in diverse settings, therefore justifying an emphasis on affordable and accessible SUs. Additionally, the encouragement of GLP-1 and SGLT-2 prescription when aiming to minimize hypoglycemia and manage weight could drive uptake of these classes, which we would love to see. In addition to retaining a table of drug- and patient-specific factors to consider (table 9.1), the 2019 Standards also still have an extensive table of information on the average cost of different drug classes (table 9.2).

  • Also included in this section is a somewhat complex, at least in appearance, flow chart on intensification of injectable therapy (Figure 9.2, below), which includes the novel recommendation of GLP-1 agonists as first-line injectable therapy ahead of basal insulin (save in particular circumstances). This is easily one of the most notable single changes to the 2019 Standards and – in keeping with the theme of this edition – is also driven by the ADA-EASD Consensus Report. While this figure is quite complex at first glance, we actually think it adds substantial value: It is a far more prescriptive figure than analogous figures in recent Standards (see figure 8.2 from the 2018 Standards), and we imagine many HCPs – and especially PCPs – will find it easier to process and practice this treatment cascade compared to past presentations of the info. Moreover, we remain thrilled to see GLP-1s promoted over basal insulin, given preferable effects on weight, the option of once-weekly dosing, little to no hypoglycemia risk, and long-term beta cell preservation; we’ve seen this recommendation received with impressive enthusiasm among thought leaders.

  • Interestingly, the section on noninsulin treatments for type 1 diabetes was abbreviated in the 2019 Standards, “as these are not generally recommended.” This section was abbreviated from 455 words in 2018 to 259 in 2019 – in other words, short to shorter. We can understand ADA’s reluctance to write about off-label use of drugs in type 1, but we’re surprised that they would shorten this section given that use of adjunct therapies for type 1 diabetes is only becoming more common. It seems very strange to minimize this increasingly important information. While the section still mentions all the same classes of medication as in the past, it is much shorter, and we hate to think that HCPs may struggle to find or access critical information about using these therapies safely in type 1. On this note, we were informed by ADA that it recognizes the unmet need for additional and adjunctive therapies for individuals with Type 1 diabetes. As the Standards reports on approved indications, the abbreviated section should not be interpreted as this area not being important. As new evidence is obtained and when moving toward an indication, this clearly will be updated.

  • There was a single (one!) but meaningful new sentence on Mannkind’s Afrezza (inhaled Technosphere insulin). In reference to the recently published STAT study (Afrezza vs. NovoLog), ADA emphasized that supplemental doses of Afrezza beyond the mealtime dose can be taken without fear of hypoglycemia or weight gain – with the caveat that a larger study is needed to confirm this result.

  • To aid hypoglycemia risk assessment, these Standards include a novel table detailing factors that increase risk of treatment-associated hypoglycemia. While quite simple and straightforward (see below), our feeling is that this table holds particular value to HCPs in deciding whether the need to minimize hypoglycemia is the most important factor to consider in the above treatment algorithm. We reiterate, of course, that hypoglycemia is an important consideration for all people with diabetes, but this table could be very useful in this aspect of clinical decision making – though we wonder if it wouldn’t be more useful in the chapter on pharmacology (it’s currently housed in chapter 4, “Comprehensive Medical Evaluation and Assessment of Comorbidities”)?

Cardiovascular and Kidney Disease Recommendations: Deep Dive

  • Also mirroring the ADA/EASD Consensus Guidelines published this October, SGLT-2 inhibitors and GLP-1 agonists are explicitly recommended for patients with established ASCVD or CKD. This recommendation builds on the 2018 ADA Standards of Care, which for the first time added CV recommendations to its treatment algorithm. Specifically, SGLT-2s are recommended over GLP-1s for patients with ASCVD who have predominant heart failure or CKD, while either a GLP-1 or SGLT-2 is recommended in the case that ASCVD predominates (given adequate eGFR for the latter). On this front, we continue to think it’s quite progressive that ADA has integrated both heart failure and CKD into this algorithm, given a relative lack of primary endpoint evidence compared to traditional MACE outcomes – a decision that we certainly applaud (though to our understanding the CKD component is a C level recommendation). This year’s Standards of Care also incorporated additional text to acknowledge heart failure as an important type of CV disease in people with diabetes (see the dedicated section on HF in Section 10), reflecting both (i) the wealth of data that has emerged on the potential for SGLT-2s in reducing risk of this complication and (ii) increasing recognition in the field of the morbidity and mortality associated with heart failure. We imagine that this focus will only grow in the coming years, especially with thought leaders coalescing around the idea of using SGLT-2 earlier on in diabetes care with the intention of reducing HF events from the get-go.

  • As in the ADA-EASD Consensus Report, this recommendation ranks GLP-1s as liraglutide > semaglutide > exenatide, in terms of strength of evidence on cardiovascular outcomes. As we’ve noted in the past, we’re a bit surprised by the definitive placement of liraglutide ahead of semaglutide, especially considering semaglutide’s strikingly positive results in the (admittedly smaller scale) SUSTAIN 6 trial. We’re very curious to see how the recommendations will integrate findings from REWIND (the CVOT for Lilly’s Trulicity), which enrolled a majority primary prevention population, though we’ll have to wait for presentation of results at ADA 2019.

  • Similarly, for SGLT-2s, the document notes modestly stronger evidence for empagliflozin vs. canagliflozin; we still presume that safety signals for canagliflozin – namely amputation risks – may have contributed to this ranking. Notably, dapagliflozin is not included in this treatment algorithm, despite the presentation of results for the DECLARE CVOT at AHA 2018 in November, demonstrating a significant benefit on the primary composite endpoint of HHF and CV death in a majority primary prevention population. Our suspicion is that the authors wanted these recommendations to align with the ADA-EASD Consensus Report, which was finalized before publication of DECLARE results. In many ways, this is unfortunate given DECLARE offers the most robust (statistically speaking) evidence of a heart failure benefit with SGLT-2s to date, and we hope ADA can incorporate this new evidence swiftly. We have confirmed with the ADA the DECLARE results were not out at the time of production and are currently under review by the PPC for a living Standards of Care update in early 2019.

  • As a reminder, Lilly/BI’s Jardiance (empagliflozin), J&J’s Invokana (canagliflozin), and Novo Nordisk’s Victoza (liraglutide) are the only antihyperglycemic medications on the market with an approved cardiovascular label indication in the US.

  • In its press release, ADA highlights that for the first time, ACC is endorsing the cardiovascular disease management chapter in the Standards of Care. A statement from ACC Vice President Dr. Richard Kovacs accompanies this announcement, underscoring the shared goal of both organizations in reducing “the burden of cardiovascular disease that too often follows a diabetes diagnosis.” This endorsement does not come as a surprise but is a big deal – last month, the ACC published its first-ever consensus statement on novel therapies for CV risk reduction in type 2 diabetes, in cooperation with ADA. This consensus statement exactly matches the recommendations seen in these Standards of Care and the ADA/EASD consensus statement, reflecting the highly united front these organizations have begun to present on diabetes and CVD.

  • ADA no longer promotes a universal blood pressure target of <140/90 mmHg, instead underscoring the importance of target individualization based on CV risk. This was an expected change, seeing as last year’s Standards of Care continued to use >140 mmHg systolic as the mark for high blood pressure, despite updated ACC/AHA guidelines indicating >130 mmHg (systolic) as the threshold for hypertension. For patients with high CV risk, a blood pressure target of <130/80 mmHg is recommended; for those with low CV risk, the target is shifted to <140/90 mmHg. We’re glad to see greater agreement between ADA, ACC, and AHA on this front, and salute the thorough emphasis on personalization.

  • The ADA now also endorses the use of ACC’s ASCVD risk calculator for the assessment of 10-year ASCVD risk, with a B-level recommendation.  In previous years, ADA’s Standards of Care have shied away from endorsing this tool, citing the tool’s lack of consideration of diabetes duration and other complications in calculating CV risk (page 100). However, ADA has done an about-face, stating that this tool has utility in predicting CV risk in people with diabetes and should be used to better stratify ASCVD risk and guide therapy. We’re curious what prompted this change of heart from the ADA on the tool’s validity, and we wonder what impact this has had and will have on its use among HCPs. In conversation with our team, ADA noted that this change represents a desire to equip clinicians with tools to assess their patients’ risk of ASCVD to help them determine optimal blood pressure targets. Seeing as individualized blood pressure goals differ depending on CVD risk, providers need a useful tool in order to estimate that risk.

  • A comprehensive overview of the majority of CVOT data available to-date is outlined in Table 10.4.  Section 10 of the sprawling Standards of Care features a dedicated focus on the intersection of antihyperglycemic therapies and cardiovascular outcomes. CVOT data from EMPA-REG OUTCOME, CANVAS and CANVAS-R, LEADER, EXSCEL, SUSTAIN-6, ELIXA, and HARMONY Outcomes are all discussed in depth in separate paragraphs. Data from DPP-4 inhibitor CVOTs – including SAVOR TIMI 53, EXAMINE, and TECOS – are also included in Table 10.4. Notably, however, recently reported data from DECLARE and CARMELINA are not included in this document, and we hope to see inclusion of this data in the “living” Standards before the 2020 edition is published. Notably, we learned from ADA that full data from DECLARE and CARMELINA will also be read-out at ADA 2019.


--by Ann Carracher, Martin Kurian, Peter Rentzepis, Maeve Serino, and Kelly Close