New Year and New Guidelines: Incorporating Cardiovascular Outcome Data

After a long year of being on the look-out for new cardiovascular outcome trial (CVOT) data, the American Diabetes Association (ADA) has released the much anticipated 2017 Standards of Medical Care in Diabetes update. The overall value of the CVOT data has been called into question and clinicians have varied predictions regarding how the ADA may incorporate those findings into their recommendations.  So let’s take a look:

The ADA has incorporated their recommendation regarding the positive outcomes seen with the use of empagliflozin in the EMPA-REG OUTCOME trial and liraglutide in the LEADER trial into the section on the pharmacologic approaches to glycemic treatment in type 2 diabetes mellitus (T2DM). Regretfully, the data was not incorporated into the general treatment algorithm, which continues to focus on patient centered characteristics for the selection of second line agents. Instead, the level B ADA recommendation comes with some caveats. The recommendation outlines the use of empagliflozin and liraglutide in patients with long-standing, poorly controlled T2DM and established atherosclerotic cardiovascular disease (ASCVD) in addition to the existing standards of care. (ref 1)  These guideline updates are on the heels of the new indication approval by the FDA for empagliflozin. This new indication is to reduce the risk of cardiovascular death in adults with T2DM and cardiovascular disease.(ref 2)

While this blanket statement for established ASCVD may by easier for clinicians to apply in practice, it is important to recognize the differences in patient population that were included in both the EMPA-REG OUTCOME and the LEADER trials.(ref 3,4) The LEADER trial exemplified a higher level of external validity, because of the more inclusive study design and expansive definition of high cardiovascular risk. (ref 4) While the EMPA-REG OUTCOME study included patients with only established cardiovascular disease, the LEADER trial also included patients with at least one cardiovascular disease risk factor and aged > 60 years. (ref 3,4) The LEADER trial also considered CKD stage 3 or greater or CHF of NYHA class II or III in their definition of coexisting cardiovascular condition, which only had an inclusion age cut off of 50 years.(ref 4) I feel that in my practice, while established ASCVD is not rare, the positive CVOT data can be applied more widely for liraglutide than for empagliflozin due to the broader inclusion criteria seen in the LEADER study.

How do the differences in study population affect how other clinicians apply this data? I am eager to hear other opinions in the clinical community about how the ADA has classified this data and if it will change your practice. Another clinical discussion starter can also be if this data fulfils the original purpose of CVOT and if they are worth the large cost and limited external  . Lastly, does anyone think that metformin with be over-thrown from the high castle as the backbone of therapy with any of this CVOT data? If you aren’t convinced just yet, what do you think it would take to convince you?

  1. American Diabetes Association (ADA). Standards of medical care in diabetes 2017. Diabetes Care 2017 Jan; 40 (Supplement 1): S64-S74.
  2. FDA approves Jardiance to reduce cardiovascular death in adults with type 2 diabetes. Available at: http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm531517.htm. [Accessed January 10, 2017]
  3. Zinman B, Wanner C, Lachine JM, et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med 2015;373:2117-28.
  4. Marso SP, Daniels, GH, Brown-Frandsen K, et al. Liraglutide and cardiovascular outcomes in Type 2 diabetes. N Eng J Med 2016;375(4):311-22

 

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Low hanging fruit

Hopefully everyone had a good holiday break, and maybe even the chance to curl up with a good book…or better, with the Federal Register!  Yes, you heard that right, the Federal appleRegister from 2016 has a number of positive developments in areas that are or will soon be ‘ripe’ for pharmacist intervention.  Notices and rulemaking for Medicare are published by CMS in the Federal Register. These notices are often accompanied by CMS’ responses to comments received on proposed rulemaking as well as some interesting background data.  So let’s look at what CMS considers important (i.e. what they are willing to pay for).  First, they recognize that medication misadventures often result in costly adverse effects including ED visits and hospitalizations.  They recognized MTM as needed (Ref 1), and when it was clear that it wasn’t being used as often as they wanted, they expanded the criteria to qualify more patients for MTM.  Realizing that medication misadventures were more likely during care transitions, CMS decided to reimburse for Transitional Care Management (CPT 99495, 99496) that included Medication Reconciliation. (Ref 2) With CMS’ announced aggressive plan to move to a system of more value-based reimbursement, new payment models were recently release as MACRA-MIPS (Ref 3), and medication reconciliation was a key component for the Merit-based Incentive Payment System (Ref 3, see pgs 77225 and 77230).

Switching gears to a key condition recognized by CMS, diabetes, it is clear that they value Diabetes Self Management Education (CPT G0108, G0109), and that they have increased the reimbursement for provision of that service. (4) Recently, CMS has announced that it will reimburse diabetes prevention in the proposed Medicare Diabetes Prevention Program (Ref 5, see section III.J)  The preliminary structure proposal is in Ref 5, and establishes how you can be prepared for the final rulemaking in 2017, and implementation in 2018.  In this document you can find links to the proposed standards and to the proposed curriculum developed by CDC. This is a must read if you want to be prepared to offer this service!

Finally, CMS has not only established reimbursement for Chronic Care Management (CPT 99490), but updated their rules with new codes for more complex patients who are involved in CCM (CPT 99487-99489) so that the reimbursement could better reflect the amount of work involved with CCM in highly complex patients (Ref 5, see section E.4 and Table 11).  As most of you already know, CCM can be provided to patients with 2 or more chronic diseases, and thus nearly all your patients with diabetes would qualify.

It is clear that medications, diabetes and chronic care are not only on the CMS’ radar screen, but they are addressing concerns related to expansion of these services as well as augmenting reimbursement.  Members of the ACCP Endocrine & Metabolism PRN are particularly well positioned to take advantage of many of these services!

At the 2016 ACCP Annual Meeting in October, a session discussing TCM and CCM was poorly attended, yet just down the hall a session on PCSK-9 inhibitors was packed.  While being the local guru on pharmacodynamics of PCSK-9 inhibitors may bring personal satisfaction, providing services such as TCM, CCM, DSMT, and soon MDPP brings revenue.  We are fighting for recognition as ‘providers’, and in any fight, you are lucky when the other guy telegraphs his moves.  CMS is not telegraphing, they are shouting it from the rooftops, yet only a few ACCP members are doing any of these services.  My bias is obvious, if you want to be recognized as ‘providers’, then start providing what your customer wants!

  1. The Medicare Prescription Drug, Improvement, and Modernization Act of 2003. Public Law 108-173. December 8, 2003. Available at: http://www.gpo.gov/fdsys/pkg/PLAW-108publ173/content-detail.html. [accessed 12/27/2016]
  2. https://www.cms.gov/Outreach-and-Education/Medicare-Learning-Network-MLN/MLNProducts/Downloads/Transitional-Care-Management-Services-Fact-Sheet-ICN908628.pdf [accessed 12/27/2016]
  3. Medicare Program; Merit-Based Incentive Payment System (MIPS) and Alternative Payment Model (APM) Incentive Under the Physician Fee Schedule, and Criteria for Physician- Focused Payment Models. Federal Register / Vol. 81, No. 214 / Friday, November 4, 2016 / Rules and Regulations. https://www.federalregister.gov/documents/2016/11/04/2016-25240/medicare-program-merit-based-incentive-payment-system-mips-and-alternative-payment-model-apm [accessed 12/27/2016]
  4. Medicare Benefit Policy Manual Chapter 15 – Covered Medical and Other Health Services https://www.cms.gov/Regulations-and-Guidance/Guidance/Manuals/downloads/bp102c15.pdf [accessed 12/27/2016]
  5. Medicare Program; Revisions to Payment Policies Under the Physician Fee Schedule and Other Revisions to Part B for CY 2017; Medicare Advantage Bid Pricing Data Release; Medicare Advantage and Part D Medical Loss Ratio Data Release; Medicare Advantage Provider Network Requirements; Expansion of Medicare Diabetes Prevention Program Model; Medicare Shared Savings Program Requirements. https://www.federalregister.gov/documents/2016/11/15/2016-26668/medicare-program-revisions-to-payment-policies-under-the-physician-fee-schedule-and-other-revisions [accessed 12/27/2016]

Co-Pays and Policy

An recent editorial in New England Journal of Medicine (N Engl J Med 2016; 375:2013-2015) from Dr. Leemore Dafny and others spoke of the U.S. DHHS announced goal of linking at least 50% of Medicare spending to value-based payment models. They noted that “health care providers are now scrambling to reorganize in a way that delivers value while preserving or enhancing ‘commercial success’ […of their health care businesses]…For years, insurers and pharmacy benefits managers have steered consumers toward generic and other ‘high-value’ drugs by categorizing drugs into ‘tiers’ and requiring lower copayments for ‘preferred’ drugs.” High value and preferred decisions are being made by the insurer/PBM based perhaps on criteria other than what a clinical pharmacist might consider high value… The authors note that “under tiering, insurers offer manufacturers favorable tier placement in exchange for better discounts” a clear benefit to the insurer or PBM. “Placement on a preferred-brand tier, with a [low] co-pay, will [arguably] yield higher sales than placement on a non-preferred-brand tier with a typical copayment of more than $50. Insurers can also negotiate lower prices for drugs that have therapeutic substitutes or questionable benefits by threatening to exclude them from their formularies entirely.”  The philosophy espoused by the authors of the article is that this is all good!  However, they note that the pharmaceutical industry “counterattacked” (…interesting choice of emotional vocabulary) “by offering ‘copayment coupons’. These coupons or discount cards — distributed by physicians’ offices, through the mail, and online — enable the manufacturer to pay some or all of a consumer’s copayment for a prescription. By severing the link between cost sharing and the ‘value’ generated by a drug, copayment coupons can undo the perceived beneficial effects of tiering.”  They estimate that “coupons increase the percentage of prescriptions filled with brand-name formulations by more than 60%” (!)

OK, I get it! The tiering process is one way to control costs, and healthcare policymakers like that!  I wanted to present a flip side view from the patient care perspective. It is well known that medication adherence is related in part to the size of co-pay assessments in an attempt at ‘cost sharing’ (1-2) both generally and for those entering the Medicare ‘donut hole’.(3)  The use of ‘high value’ [my definition is not necessarily based on medication cost…] drugs such as those that are still branded, may offer improved outcomes, but they are often made second or third tier by insurers to limit their own costs.   Adherence with a number of new medications, especially those with minimal co-pays suggests that there are adherence benefits to be gleaned from the discount cards or coupons.  Add to that the evidence that some of the older diabetes medications, available with little or no co-pays may have a higher rate of adverse effects. (4-7)

So ask yourself, if your mother or father were diagnosed with type 2 diabetes, would you want early aggressive therapy with agents that may have significantly more benefits (8-9), not to mention the benefit of early glucose control, or would you want them to start older agents (some with potential CV risk) and then stay with them for years in the clinical inertia that plagues diabetes care. I know what the policy makers prefer, and I know what my preference is for making new and better drugs more available regardless of ability to handle the co-pay…How about you?

  1. Effect of prescription copayments on adherence and treatment failure with oral antidiabetic medications. Barron J, Wahl P, Fisher M, Plauschinat C. P.T. 2008 Sep;33(9):532-53
  2. How patient cost-sharing trends affect adherence and outcomes: a literature review.Eaddy MT, Cook CL, O’Day K, Burch SP, Cantrell CR. P T. 2012 Jan;37(1):45-55
  3. Part D coverage gap and adherence to diabetes medications. Gu Q1, Zeng F, Patel BV, Tripoli LC. Am J Manag Care. 2010;16(12):911-8
  4. Sulphonylureas and risk of cardiovascular disease: systematic review and meta-analysis. Phung OJ1, Schwartzman E, Allen RW, Engel SS, Rajpathak SN. Diabet Med. 2013 Oct;30(10):1160-71
  5. Hyperinsulinemia and sulfonylurea use are independently associated with left ventricular diastolic dysfunction in patients with type 2 diabetes mellitus with suboptimal blood glucose control. Inoue T, Maeda Y, Sonoda N, Sasaki S, Kabemura T, Kobayashi K, Inoguchi T. BMJ Open Diabetes Res Care. 2016 Aug 18;4(1):e000223
  6. Cardiovascular risk associated with the use of glitazones, metformin and sufonylureas: meta-analysis of published observational studies.Pladevall M, Riera-Guardia N, Margulis AV, Varas-Lorenzo C, Calingaert B, Perez-Gutthann S. BMC Cardiovasc Disord. 2016 Jan 15;16:14
  7. Mortality risk among sulfonylureas: a systematic review and network meta-analysis.Simpson SH, Lee J, Choi S, Vandermeer B, Abdelmoneim AS, Featherstone TR. Lancet Diabetes Endocrinol. 2015 Jan;3(1):43-51
  8. Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. Zinman B, Wanner C, Lachin JM, Fitchett D, Bluhmki E, Hantel S, Mattheus M, Devins T, Johansen OE, Woerle HJ, Broedl UC, Inzucchi SE; EMPA-REG OUTCOME Investigators. N Engl J Med. 2015 Nov 26;373(22):2117-28
  9. Empagliflozin and Progression of Kidney Disease in Type 2 Diabetes. Wanner C, Inzucchi SE, Lachin JM, Fitchett D, von Eynatten M1, Mattheus M, Johansen OE, Woerle HJ, Broedl UC, Zinman B; EMPA-REG OUTCOME Investigators. N Engl J Med. 2016 Jul 28;375(4):323-34

Chronotherapy: Underutilized or Underwhelming in Diabetes and Hypertension?

The standard treatment of hypertension in patients with diabetes focuses on attaining blood pressure less than 140/90 or 130/80 mmHg in young patients with ASCVD risk factors. The renal/cardio protective effects of ACEI/ARBs in patients with diabetes also makes this class heavily utilized. While ACEI/ARB benefits are well documented, the best administration time for these agents is unclear. In fact, the 2016 ADA Guidelines reads “Consider the administration of antihypertensives at bedtime,” which is not exactly clear guidance or a glowing endorsement of bedtime dosing.

Chronotherapy involves the purposeful administration of antihypertensive pharmacotherapy at specific times to target the circadian rhythm of blood pressure. A patient with a normal 24-hour circadian blood pressure pattern has the lowest pressures during sleep-time (dipping) and the highest during the awakening period. This rise in blood pressure in the morning is commonly referred to as the “morning surge” and is the most common time period for cardiovascular events.

Several cohort studies now suggest that nighttime blood pressure may be the best predictor of cardiovascular disease compared to clinic, 24-hour, and daytime pressure using ambulatory blood pressure devices. Patients in these trials who did not exhibit a 10% decrease in blood pressure at night were classified “non-dippers” and were at increased risk for cardiovascular morbidity and mortality. Therefore, in management of hypertension, chronotherapy typically is characterized by nighttime dosing of anithypertensives to convert non-dippers to dippers.

Abundant evidence clearly indicates that bedtime dosing of ACEIs and ARBs is more effective in decreasing nighttime blood pressure compared to morning administration. Additionally, nighttime dosing of ACEI/ARBs may also help with daytime control. On the other hand, evidence for calcium channel blockers varies and diuretics are generally avoided because awakenings secondary to nocturia would prevent patients from dipping. ACEIs and ARBs improve the circadian patterns by lowering nighttime blood pressure, but the question remains on whether this intervention improves clinical outcomes.

  1. To date, only one trial large trial has investigated chronotherapy’s effects on cardiovascular outcomes. The MAPEC trial (Monitorización Ambulatoria para Prediccion de Eventos Cardiovasculares [i.e., Ambulatory Blood Pressure Monitoring for Prediction of Cardiovascular Events] randomized patients to take at least one blood pressure medication at bedtime or all medications upon awakening. After a median follow up of 5.6 years, the group randomized to bedtime administration of at least one antihypertensive medication had a 61% (HR 0.39; p<0.001) lower risk of total events compared to the group administering antihypertensives upon awakening. Furthermore, approximately 20% of MAPEC’s population included patients with diabetes whose results were equally impressive. (Hermida R, et al. Diabetes Care. 2011;34:1270).
  1. The evidence for chronotherapy on clinical outcomes is moderate in nature. However, safety must be considered before implementing this strategy. The HOPE trial investigated the effects of Ramipril taken at night compared to placebo in high risk patients. While this trial cannot answer questions regarding efficacy, it did illustrate an adequate safety profile in a patient population required to have one of the following: coronary artery disease, peripheral vascular disease, stroke, or diabetes plus one ASCVD risk factor(Yusuf S, et.al. New Engl J Med. 2000;342:145).
  1. Another safety consideration in chronotherapy is adherence. The adherence rate in chronic diseases is currently poor, roughly 50-60%. One prescribing trait contributes to the overall non-adherence rate is “timing adherence.” Timing adherence compares once daily to twice daily dosing regimens with the latter illustrating a nearly 28% decrease in adherence (Coleman C, et al. J Manag Care Pharm.2012;18:527). This is clearly an alarming statistic and applies to patients taking medications at different times in the day, including those instructed to take an ACEI or ARB at night.

More studies are needed to document outcomes with bedtime dosing of ACEI or ARBs, and whether once daily dosing at bedtime is associated with better adherence.  Also, the question of “quasi-adherence” [taking the medication “some” or “most” nights] and its effect on outcomes would be important. The evidence does seem to indicate that patients would benefit from chronotherapy, especially patients with diabetes, but careful monitoring of adherence must be done to prevent worsening control. My advice is to select patients carefully using a patient-centered approach and to use chronotherapy in patients with diabetes and uncontrolled hypertension.

Are you using chronotherapy in your practice? Are you monitoring adherence…and how?

How can pharmacists help patients with diabetes bridge the inpatient-to-outpatient transition of care gap?

In the very large tertiary care academic medical center where I work as a clinical pharmacist, nearly 30% of all patients have diabetes. Most already carry the diagnosis in their past medical history at the time of admission, but many are new to the diagnosis (although admitted for other reasons). Despite this high prevalence of diabetes, my hospital does not have a dedicated certified diabetes educator (CDE). Shocked? You shouldn’t be. The days of a dedicated hospital-based diabetes educator whose sole job is to provide comprehensive diabetes self-management education (DSME) are long gone in many institutions because hospital administrators believe it is inefficient to pay a CDE to run around the hospital to teach patients with diabetes.

There are many challenges associated with hospital discharge planning for patients with diabetes. These challenges include pressures to discharge the patient early, treatment inertia, and knowledge deficits among practitioners and nursing staff regarding management of diabetes and insulin therapy.1 Patients are very sick with whatever disease process brought them into the hospital. There is high acuity, and short lengths of stay. But, there are also very good reasons that patients, even those who might have been educated prior to admission, need diabetes education. For example, insulin is the mainstay for glucose management in the hospital setting. This means that nearly all patients new to the diagnosis are given insulin, patients taking non-insulin therapy prior to admission have that therapy switched to insulin, and patients on insulin prior to admission have their insulin therapy changed to the insulin products “on formulary”. Patients, both those new to the diagnosis and those who have carried the diagnosis for years, are often confused about their diabetes management during and following hospitalization.

Diabetes self-management education provides the foundation for self-care and has been shown to improve health outcomes and glycemic control.2 Admittedly, DSME should occur in the outpatient setting when the patient is feeling better and is ready to fully participate in the education effort; however, hospitalized patients need to be taught how to safely manage their diabetes until they have the opportunity for comprehensive education as an outpatient.3,4 In a prospective non-randomized pilot study, hospitalized patients receiving targeted survival skill education from trained research assistants had improvement in diabetes knowledge and medication adherence.5 In a retrospective analysis of hospitalized patients with poor glycemic control (A1C >9%), patients who received formal education from a trained diabetes nurse educator had lower all-cause readmission rates.6

Despite these data, the burden of diabetes education is often placed on staff nurses in the hospital setting. Theoretically, bedside nurses are in an excellent position to provide patient education since they are in and out of the patient’s room multiple times each day to administer medication and perform their other nursing duties. Since they are near the patient at all times, they can find teachable moments when the patient is awake and able to mentally and physically participate in educational efforts. Unfortunately, bedside nurses have limiting opportunities for training in diabetes-specific topics and they lack confidence in providing accurate information on current therapies.7 In addition, there are often high turn-over rates and/or reliance on resource (or registry) nurses who may not be familiar with the expectation of providing diabetes education.

I am often asked by my nurse colleagues to assist with insulin education for patients who are new to insulin therapy. Despite all my efforts to try to get notified of these patients prior to the day of discharge, the “asks” typically come on the day of discharge because there is a delay in identification of the education need. I get excuses like “well, we just realized the patient needs to go home on insulin”, even though the patient had been here for 4 days, had an A1C of 12% on the day of admission, and has had continued hyperglycemia despite daily upward titration of insulin doses since the day of admission. Unfortunately, there are so many competing demands for the patient’s time during hospitalization, and especially on the day of discharge. When I try to see patients, they are often away at a procedure or otherwise unavailable to me when I get to the room. They are bombarded with people needing to see them – consult teams, physical therapists, social workers, respiratory therapists, etc.

I suppose that I empathize with hospital administrators who don’t want to pay a CDE to run around and only see a mere fraction of diabetes patients, but patients need to understand medication changes that are made during hospitalization and what they should do following hospitalization. Patients need to know how going home will affect their glucoses, especially if they are discharged with a steroid taper or have TPN discontinued on the day of hospital discharge. If patients are new to insulin, then they need to know how to administer it, how to monitor their glucoses, and how to identify and treat hypoglycemia. In the real-world setting, how can we ensure that patients receive the appropriate survival skills education prior to discharge – and not wait until the day of discharge to actually give it to them? Providing educational resources and tools to bedside nurses is certainly one answer;7 however, it is likely not enough.

Patients with diabetes have a 30-day readmission rate of 14-23%.8 A comprehensive plan to prevent hospital readmissions for patients with diabetes is definitely needed. We know that hospitalized patients who received a single 30- to 45-minute counseling session with a pharmacist prior to discharge had greater adherence rates with their diabetes medications and follow-up appointments, and a reduction in A1C compared to a control group receiving nurse-directed standard-of-care education.Besides education, other interventions that may reduce the risk of early readmission for patients with diabetes include improving communication of discharge instructions, involving patients more in medication reconciliation, and addressing barriers to follow-up care.10 Pharmacists are well-suited to take a major role in delivering these types of interventions. So, why aren’t there more pharmacists providing this type of care?

  1. Cook CB, Seifert KM, Hull BP, et al. Inpatient to outpatient transfer of diabetes care: planning for an effective hospital discharge. Endocr Pract. 2009;15(3):263–9.
  2. Chrvala CA, Sherr D, Lipman RD. Diabetes self-management education for adults with type 2 diabetes mellitus: A systematic review of the effect on glycemic control. Patient Educ Couns. 2016;99(6):926-43.
  3. American Association of Diabetes Educators. Diabetes inpatient management. Diabetes Educ. 2012;38(1):142–6.
  4. Moghissi ES, Korytkowski MT, DiNardo M, et al. American Association of Clinical Endocrinologists and American Diabetes Association consensus statement on inpatient glycemic control. Endocr Pract. 2009;15(4):353-69.
  5. Magee MF, Khan NH, Desale S, Nassar CM. Diabetes to Go: Knowledge- and Competency-Based Hospital Survival Skills Diabetes Education Program Improves Postdischarge Medication Adherence. Diabetes Educ. 2014;40(3):344-50.
  6. Healy SJ, Black D, Harris C, Lorenz A, Dungan KM. Inpatient diabetes education is associated with less frequent hospital readmission among patients with poor glycemic control. Diabetes Care. 2013;36(10):2960-7.
  7. Krall KS, Donihi AC, Hatam M, Koshinsky, J, Siminerio L. The Nurse Education and Transition (NEAT) model: educating the hospitalized patient with diabetes. Clinical Diabetes and Endocrinology.2016, 2:1.
  8. Rubin DJ. Hospital readmission of patients with diabetes. Curr Diab Rep. 2015;15(4):17.
  9. Shah M, Norwood CA, Farias S, Ibrahim S, Chong PH, Fogelfeld L. Diabetes transitional care from inpatient to outpatient setting: pharmacist discharge counseling. J Pharm Pract. 2013;26(2):120-4.
  10. Rubin DJ, Donnell-Jackson K, Jhingan R, Golden SH, Paranjape A. Early readmission among patients with diabetes: a qualitative assessment of contributing factors. J Diabetes Complications. 2014;28(6):869-73.

Insulin Costs – Why are they Rising?

Insulin is a mainstay of therapy for both type 1 and type 2 diabetes. It has been around since 1921 when Banting and Best discovered it. Over the years we have gotten away from animal sources, modified organisms to produce it in large quantities, and increased the capacity to do so … a classic scenario for lowering the price! If that’s the case, why is it still so expensive … and increasing faster in recent years than in the past? Yes, we know that making a biological agent is not cheap, and there are concerns for stability, and other factors that could be invoked to explain the price increase but if patients need it and can’t afford it, what’s the point of this sudden rise in insulin(s) cost?

Working in the diabetes world when insulin cost has increased in some cases by 200% and in others by 600% between 2002 and 2013 seems inconceivable.1 Compare this to other countries where the cost of insulin seems more reasonable with Lantus® costing approximately $6 per vial and Humulin® NPH costing $3 per vial in India.2,3 Newer insulins have been added in the past year elevating the price game as well, but it is easier to explain at least some component of higher price with more ‘benefit’… although those additional benefits seem smaller with each new product. There is a little hope with generic alternatives such as Basaglar® (insulin glargine) becoming available along with Wal-mart’s cheaper Novolin Relion® 70/30 being approximately $25 a vial compared to Novolin® 70/30 prices at other facilities costing approximately $145.4 If that wasn’t enough, add into the picture PBMs where the preferred insulins change in some cases on a yearly basis and it’s understandable as to why the use of insulins can be an even more subject for both providers and patients heaped onto the striking increases in cost!

Now let’s think about our Medicare patient. They usually have a fixed budget and those patients with diabetes are often on at least 3-4 other medications for prevention of complications, which does not even take into account other medical conditions. Just looking at a patient prescribed a long-acting insulin, rapid-acting meal time coverage, an ACE inhibitor or angiotensin-receptor blocker (ARB) for hypertension or nephropathy, and a statin for dyslipidemia, they will hit the Medicare gap in approximately July when utilizing Lantus® and Novolog® compared to not entering it when utilizing the Novolin ReliOn® products. However, what is the quality of glycemic control?

Should patients on fixed incomes and at a lower income level be subjected to different care than those without income issues? Let’s also not forget that most Medicare patients don’t qualify for patient assistance programs that could help with more expensive standard of care insulin products.

This rising cost of insulins has caught the attention of the American Diabetes Association (ADA) who published a press release in February 2016 advocating for 3 changes: 5

  • Wanting to see all off-patent diabetes medications, including insulin, in the lowest cost-sharing tier on all formularies;
  • Supporting the authorization of the Centers for Medicare and Medicaid Services (CMS) to negotiate prices for prescription drugs under Medicare Part D; and
  • Supporting the move toward value-based benefit design from the current fee-for-service system to incentivize better outcomes, in addition to promoting adherence to recommended therapy to reduce emergency department visits and hospitalizations.

In addition, one of the leading experts in the field of diabetes, Dr. Hirsch presented a talk at the 2015 ADA national meeting discussing the issue of rising costs of insulins. He advocates a call for change and action by not only by the national organizations, lobbyists, insurance companies, hospitals, patients, and providers, but also for a need to educate students, residents and fellows in the treatment of diabetes utilizing human insulins.6

Why are insulins still so expensive in the United States? Why are the prices of insulins allowed to increase like this when for some patients it is a matter of life or death? Overall, it is appalling that insulin costs overall are rising rather than decreasing and it seems like something needs to be done. So what are we going to do about it? Any thoughts?

 

  1. Hua X, Carvalho N, Tew M, Huang ES, Herman WH, Clarke P. Expenditures and prices of antihyperglycemic Medications in the United States: 2002-2013. JAMA. 2016;315:1400-1402.
  2. Medindia Network for Health. Lantus (insulin glargine) price list. Available at: http://www.medindia.net/drug-price/insulin-glargine/lantus.htm. Accessed 7/25/16.
  3. Medindia Network for Health. Huminsulin-N (insulin) price list. Available at: http://www.medindia.net/drug-price/insulin/huminsulin-n.htm. Accessed 7/25/16.
  4. Novolin 70/30. Good Rx. http://www.goodrx.com/novolin-70-30. Accessed 7/25/16.
  5. American Diabetes Association. Statement on Accessibility and Affordability of Diabetes Medications. http://www.diabetes.org/newsroom/press-releases/2016/statement-on-accessibility-and-affordability-of-diabetes-medications.html. Accessed 7/25/16.
  6. Hirsch IB. Changing costs of insulin therapy in the U.S. Available at: http://webcasts.diabetes.org/html5Player/default.aspx?webcastXmlInfo=http://webcasts.diabetes.org/netadmin/Content/ADA2015/sync/CT-SY06/38134.xml&videoBaseUrl=https://s3.amazonaws.com/ada-stream01/ADA2015/CT-SY06/. Accessed 7/26/16.

Treatment of T2DM after metformin: what’s next?

Pharmacologic options for the treatment of type 2 diabetes mellitus have expanded over the past ten years.  Metformin has remained the first-line agent due to a well-established safety and efficacy, low cost, and data demonstrating a reduction in cardiovascular events.1  It is pretty clear from a number of studies that metformin therapy should be maximized, which in some patients may require doses above 2000 mg/day. 2  Second-line treatments include a variety of agents, including basal insulin, dipeptidyl-peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, sodium-glucose cotransporter 2 (SGLT2) inhibitors, sulfonylureas, and thiazolidinediones.  Metformin is synergistic with many of the other agents, and should not be discontinued as beneficial effects can be seen even in patients taking insulin as the second line agent. 3 The 2016 treatment recommendations detail the above mentioned medications as all viable options for second-line therapy with no preference to one drug class over the other. 1 While this seems like this might open up treatment options for clinicians, it often in fact, leaves clinicians wondering about the BEST next option for their patients.  All of the options will always have a cost/benefit ratio, and so trying to choose the best agent that minimizes patient out of pocket costs is important.  In that regard, SGLT2s from all the current manufacturers have co-pay cards to minimize the cost (for patients not on Medicare).

The likely reason for no definitive recommendation for a second-line agent is that controversy exists regarding which agents should be used for the treatment of T2DM in those who cannot achieve glycemic control with metformin alone.  The newer agents, DPP-4 inhibitors, GLP-1 receptor agonists, and SGLT2 inhibitors are effective, exhibit positive/neutral effects on body weight, and pose minimal risk of hypoglycemia in comparison to other available agents to treat hyperglycemia. Trials have been completed, or are ongoing, regarding the cardiovascular effects of these agents.3-9   and in the case of empagloflozin, the results of a recent trial have resulted in the manufacturer seeking a cardiovascular risk reduction, and leading to a debate on whether FDA should grant this request (http://www.ptcommunity.com/news/2016-06-24-000000/fda-panel-vote-whether-empagliflozin-jardiance-cuts-risk-cardiac-death). 5  Thus far, CV outcomes have either been positive or neutral with these agents leading clinicians to head towards those agents even though the cost may be higher.

Recently, the FDA has issued concerns regarding the newest agents, the SGLT2 inhibitors regarding the risk for acute kidney injury and ketoacidosis leaving us scratching our heads again, especially after some data exists that there many actually be reno-protection from this drug class (http://www.dddmag.com/news/2016/01/new-data-shows-sglt2-inhibitors-may-be-effective-preventing-kidney-failure).  Time and studies will tell which may be the best second line agents, but it is always important to consider patient out-of-pocket costs especially since diabetes patients take many different medications for diabetes, hypertension, and dyslipidemia…and more.

 

 

  1. American Diabetes Association. Standards of medical care in diabetes. Diabetes Care. 2016;39(Suppl 1)
  2. Hirst JA, Farmer AJ, Ali R, et al. Quantifying the effect of metformin treatment and dose on glycemic control. Diabetes Care. 2012;35:446-454.
  3. Holden SE, Jenkins-Jones S, Currie CJ. (2016) Association between insulin monotherapy versus insuln plus metformin and the risk of all-cause mortality and other serious outcomes: a retrospective cohort study. PLoS ONE 11(5):e0153594. Doi:10.137/journal.pone.0153594.
  4. Pfeffer MA, Claggett B, Diaz R, et al. Lixisenatide in Patients with Type 2 Diabetes and Acute Coronary Syndrome. N Engl J Med. 2015 Dec 3;373(23):2247-57.
  5. Zinman B, Wanner C, Lachin JM, et al. Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. N Engl J Med 2015; 373:2117-2128.
  6. Scirica BM, Bhatt DL, Braunwald E, et al; for the SAVOR-TIMI 53 Steering Committee and Investigators. Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus. N Engl J Med. 2013;369(14):1317-1326.
  7. White WB, Cannon CP, Heller SR, et al; for the EXAMINE Investigators. Alogliptin after acute coronary syndrome in patients with type 2 diabetes. N Engl J Med. 2013;369(14):1327-1335.
  8. Zannad F, Cannon CP, Cushman WC, et al; for the EXAMINE Investigators. Heart failure and mortality outcomes in patients with type 2 diabetes taking alogliptin versus placebo in EXAMINE:  a multicentre, randomised, double-blind trial. Lancet. 2015;385:2067-2076.
  9. Van der Werf F, Armstrong P. Trial evaluating cardiovascular outcomes with sitagliptin in patients with type 2 diabetes: TECOS. Presented at ESC Congress 2015. London, England, UK. Abstract 3147.