Words…

The author Rudyard Kipling once said: “Words are, of course, the most powerful drug used by mankind.” And, we know that different ways of expressing things can have an impact on patients. It is said that ‘people experience diabetes and the language of diabetes in context.’ This goes for many acute and chronic conditions. We are moving more and more into the realm of patient-centered care, with the result being that we are (and should be) viewing patients more as individuals than in bygone days when patients in hospitals were often referred to by their disease…”the heart failure in 3B’ or the ‘lupus nephritis in 12A’. And while that has happened less and less over the years, there are still many communications with and about patients that are problematic. We often hear about what to do when patients ‘fail on metformin’, or during an office visit their diabetes is labeled as ‘uncontrolled.’ These labels of failure and lack of control when shared with or in front of a patient can have a lasting impact on their attitude and/or feelings of self-efficacy. A number of diabetes related organizations addressed the language of diabetes (1-3). Patients are decisionmakers in many medical interactions, and how the decision is framed can have a huge impact on those decisions. The words used can trigger biases, heuristics and affect the direction of therapy in nearly all medical decisions patients make (4). Community based Pharmacists continue to shift in their roles from dispensing to patient education and counseling. As community-based pharmacists and hospital or clinic-based pharmacists expand their education and counseling roles to increasingly involve, medication reconciliation, and even home visits the words used in various situations make a difference (5). This is true, of course for pharmacists practicing in the clinical environment as patient encounters related to drugs (MTM, Med Reconciliation, TCM, etc) are an ever-increasing part of the pharmacists role in clinics, hospitals and medical offices as well. Patient-centered communications or communications about patients should avoid labels either as a noun (eg “are you diabetic”) or an adjective (“that’s a diabetic foot ulcer”), should avoid designations related to control either as a noun or verb (“he has poor glucose control”). Communications of should avoid imperatives (“you really must take this medication each morning”), and should avoid terms like “non-compliant” or “non-adherent” (1). While these terms are applied to diabetes patients in these examples it is easy to see how they can translate to other conditions. In a recent study (5) that looked at home visits as a venue for patient-pharmacist communication, the most discussed topics aligned with the challenges found in other studies such as patients’ lack of knowledge about their medications and medication regimens. These discussions are potential entrees into the use of motivational interviewing as a tool to enhance patients’ motivation…key to many chronic conditions including diabetes [shameless plug: Motivational Interviewing in Diabetes Care. Steinberg MP & Miller WR. Available in the ACCP Bookstore]. Changing our words is hard, but being more conscious of how we speak to and about patients is vital to patient-centered care. Let’s all commit to making a conscious effort to observe the language we use and change it where we need to!

1) The Use of Language in Diabetes Care and Education. Dickinson J, et al Diabetes Care 2017;40:1790-1799

2) International Diabetes Federation campaign on the language around diabetes. https://www.idf.org/our-activities/advocacy-awareness/campaigns/language.html (accessed 12/12/18)

3) Diabetes Australia position statement: A new language for diabetes: improving communications with and about people with diabetes. Speight J, et al. Diabetes Research and Clinical Practice 2012;97:425–431

4) Cognitive biases and heuristics in medical decision making: a critical review using a systematic search strategy. Blumenthal-Barby JS, Krieger H. Medical Decision Making 2015;35:539-557

5) Patient‑pharmacist communication during a post‑discharge pharmacist home visit Ensing HT, et al. International Journal of Clinical Pharmacy 2018;40:712-720

Advertisements

Patient’s Dilemma…… Picking Insulin Prescription from Pharmacy vs Purchasing School Supplies for Kids

Hyma Gogineni, Pharm. D, MSc, BCACP, TTS

We all have patients in our clinics deciding to choose between buying a prescription vs paying for other supplies, posing them at a higher risk for serious health consequences.  Patients who use insulin, the quantity will be increased over time as well as the prescription costs putting these patients at increased medication expenditure. The average price of insulin has been tripled between 2002 ($231.48) and 2013 ($736.09) and the total cost of insulin was significantly higher than the other antihyperglycemic medications.1

Recently American Diabetes Association released a white paper, Insulin Access and Affordability Working Group: Conclusions and Recommendations derived from the product of meetings with representatives from major stakeholders.2 The authors concluded that insulin supply chain is a complex system and lacking transparency and making it difficult to understand the dollars flow and intermediary profits even after extensive research and stakeholder discussions.2  The average Wholesale Acquisition Cost (WAC) and National Average Drug Acquisition Cost (NADAC) for insulin increased by 15% to17% per year from2012 to 2016, as with the increased insulin prices, consumers out of pocket costs increased simultaneously.2   The current pricing and rebate system encourages high list prices, due to this list prices of insulin  has been tripled between 2002 and 2013 (Fig 1).3

ACCP E_M August Blog Fig 1

Fig 1 – Report of changes in list and net prices for Lantus.3

Regardless of the negotiated net prices by the PBMs, the cost of the insulin is greatly influenced by the list price causing high out-of-pocket costs for people with diabetes who are uninsured, or who have high deductibles or who are in the Medicare Part D donut hole.4-6 Many of us face this challenge in practice that patients with high co-pays or deductibles are less adherent to recommended dosing which can adversely impact their health. There was a shift in the prescribing patters of insulin favoring newer and more expensive insulin analogs over inexpensive human insulins which is also adding additional dollars to both healthcare system and to patients, the cost of the human insulins range from $25 to $100 per vial compared to $174 to $300 per vial for human insulin analogs.7-9 The authors stressed the importance of healthcare providers especially pharmacists role in educating patients about advantages, disadvantages, and financial implications of insulin preparations and its impact.2

As pharmacist it is essential for us to discuss with all diabetic patients about the cost of the insulin products, co-pays, availability of alternative insulin products and diabetic supplies and make them understand the true cost(s) of these products that they are receiving on a monthly/quarterly basis. This will not only change their perspectives and perhaps may enhance adherence.

Here are some of the available programs that can be an added value for both insured and uninsured patients…..

  1. Partnership for prescription assistance – helps qualifying patients without prescription drug coverage get the medicines they need for free or nearly free. https://www.pparx.org/
  2. Rxassist – offers a comprehensive database of patient assistant programs for both healthcare providers and patients. http://www.rxassist.org/
  3. NeedyMeds – is a nonprofit organization dedicated to helping people with financial assistance for their medication treatments. https://www.needymeds.org/
  4. Rx Hope – is prescription assistance organization that help people get their medicines at little or no cost. https://www.rxhope.com/
  5. BenefitsCheckup – is a prescription assistance program run by the National Council on Aging (NCOA). This program helps people over age of 55. https://www.benefitscheckup.org/
  6. CR3Diabetes – providing equipment and encouragement for people living with diabetes all over the world. https://www.cr3diabetes.org/
  7. Insulin Pumpers Foundationassist patients who do not have financial resources to purchase an insulin pump on their own. http://foundation.insulin-pumpers.org/
  8. Insulin for Life USArescues unused diabetes supplies here in the United States and deliver them across the world who have no access to these supplies. http://ifl-usa.org/
  9. Affordable Insulin Project – offers tools, resources and data can be used by a patient, caregiver, employer or healthcare professional. This site is also useful for patients with no insurance or high deductibles.  http://affordableinsulinproject.org/
  10. GoodRx – is a source for the lowest local price for all insulins and antidiabetic agents. https://www.goodrx.com/
  11. Blinkhealth – for those who do not have prescription insurance, high copays, or high-deductible with insurance plans. Blink Health offers 40% discounted price and patient has to pay online and pickup insulin in any pharmacy. https://www.blinkhealth.com/
  12. ReducedRxTM – for those with prescription coverage https://www.reducedrx.com/

Pharmaceutical programs and copay cards available for patients – please refer to the website for specific instructions

  • Note: Not all assistance programs are available to Medicare patients, be sure to check patient’s eligibility
Company Programs Copay Cards
Lilly
Lilly Cares Program – for patients with no prescription coverage, not enrolled in Medicaid or VA benefits and must meet the household guidelines. http://www.lillycares.com/ 1. Humalog U-200 Kwikpen Prescription Co-Pay card

https://www.humalog.com/u-200-kwikpen/

2. Basaglar Prescription Co-pay Card

https://www.basaglar.com/en/savings-support

3. Trulicity Savings Card

https://www.trulicity.com/diabetes-treatment-savings-card-and-support/

Novo Nordisk
NovoNordisk Patient Assistance Program (PAP) –no prescription coverage

Must be US citizen, household income <300% of federal poverty level, not enrolled in Medicare or Medicaid etc.  https://www.novocare.com/hcp/more-resources/PAP.html

1. Levmir Instant Savings Card

https://www.levemirpro.com/resources/patient-support/instant-savings.html

2. Novo Nordisk prescription savings card

https://www.rapidactinginsulin.com/novolog/save-on-novolog.html

3. Victoza Instant Savings Card

https://www.novocare.com/victoza/savings-card.html

Sanofi
Sanofi Patient Connection Program – No insurance

Must be US citizen, household income ≤ 250% of federal poverty level, not enrolled in Medicare or Medicaid etc.

http://www.sanofipatientconnection.com/patient-assistance-connection

1. Apidra No Co-Pay Savings program

https://www.apidra.com/register/default.aspx

2. Lantus co-pay card

https://www.lantus.com/sign-up/savings-and-support

3. Soliqua 100/33 co-pay card

https://www.soliqua100-33.com/savings-and-support

4. Toujeo co-pay card

https://www.toujeo.com/toujeo-savings-card-coupon-and-support

Patients with diabetes should not be deciding between purchasing an insulin vial vs. school supplies for kids, as a healthcare partner we have to make every effort to reduce the economic burden for our patients and optimal outcomes.

References

  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. Cefalu WT, Dawes DE, Gavlak G, Goldman D, Herman WH, NuysKV et al. Insulin Access and Affordability Working Group: Conclusions and Recommendations. Diabetes Care 2018 Jun;41(6):1299-1311.
  3. Roland D, Loftus P. Insulin prices soar while drugmakers’ share stays flat [article online]. Wall Street Journal, 7 October 2016.
  4. Karter AJ, Parker MM, Solomon MD, et al. Effect of out-of-pocket cost on medication initiation, adherence, and persistence among patients with type 2 diabetes: the Diabetes Study of Northern California (DISTANCE). Health Serv Res 2017;53:1227–1247.
  5. Goldman DP, Joyce GF, Zheng Y. Prescription drug cost sharing: associations with medication and medical utilization and spending and health. JAMA 2007;298:61–69.
  6. Kesselheim AS, Huybrechts KF, Choudhry NK, et al. Prescription drug insurance coverage and patient health outcomes: a systematic review. Am J Public Health 2015;105:e17–e30.
  7. Johnson CY. Why treating diabetes keeps getting more expensive [article online]. Washington Post, 31 October 2016. Available from https://www.washingtonpost.com/news/wonk/wp/2016/10/31/why-insulin-prices-have-kept-rising-for-95-years/?utm_term=.9c77afd62bb0. Accessed August 4, 2018.
  8. Luo J, Avorn J, Kesselheim AS. Trends in Medicaid reimbursements for insulin from 1991 through 2014. JAMA Intern Med 2015;175: 1681–1686 19.
  9. Lipska KJ, Hirsch IB, Riddle MC. Human insulin for type 2 diabetes: an effective, less-expensive option. JAMA 2017;318:23–24.

 

A Heart to Heart about Cardiovascular Disease in Type 2 Diabetes

Brian Terrell, Pharm.D., BCACP

This month I’d like to discuss two recent articles that have been published regarding cardiovascular disease in this exceedingly prevalent disease. In patients with diabetes, atherosclerotic cardiovascular disease is not only the leading cause of death, but is also the main contributor to the tremendous direct and indirect cost of this disease.1 However, there are signals that the incidence of this comorbidity may be improving, and we have data to support agents that can aid practitioners in continuing this trend. Cardiovascular disease risk assessment in general has also been a recent topic of interest, but is outside of the scope of this post.2

In a recent article published in Lancet, Gregg and colleagues analyzed cause specific death rates among patients with diabetes in the United States. The authors utilized data from the National Health Interview Survey conducted annually by the Center for Disease Control and Prevention’s National Center for Health Statistics.3 The data sampling covered the times from 1980 and 2014.3 The authors found that, similar to previous analyses, that adults with diabetes had significantly higher death rates from many causes including cardiovascular related deaths than their counterparts without diabetes.3 However, they found that the hazard ratio for many types of death, including vascular causes, declined over time as they moved toward more recent years.3 For death from vascular causes, the authors concluded from their data sample that the rate of death decreased 31.9% (-36.5 to -26.8, p <0.001) every ten years.3 For comparison, their results also showed a decrease in all-cause mortality (-20.1% (-24.1 to -15.9,  p<0.001)) as well as cancer related deaths (-15.7% (-24.7 to -5.7, P 0.0199)) for each ten-year period.3 In another representation of this trend, it was reported that the proportion of total deaths from vascular causes decreased from 47.8% in 1988-1994 to 34.1% in 2010-2015 for adults with diabetes.3 The authors noted that the reduction of vascular related deaths is likely to have occurred secondary to improvements in revascularization, acute care, risk factor management and societal/behavioral changes (smoking cessation, decreased trans and saturated fats).3 I encourage the blog readers to take a look at the cited article if you are interested in more data about other types of deaths other than cardiovascular related in adults with diabetes.

When it comes to agents used to treat diabetes, there have been several articles published in the recent literature regarding cardiovascular outcomes. I am sure that we are all aware of the favorable effects found in studies of liraglutide and empagliflozin and their resulting approved indication changes.4,5 In a recent systematic review and meta analyses, Zheng and colleagues set out to determine the association between the use of glucagon-like peptide 1 (GLP-1) agonists, sodium-glucose cotransporter 2 (SGLT-2) inhibitors and dipeptidyl peptidase 4 (DPP-4) inhibitors with all-cause mortality in patients treated with these agents for type 2 diabetes. The meta analysis ultimately included 236 trials and 176310 participants.6 There was a mix of comparator trials within the analysis and approximately half of the participants from each drug class were from cardiovascular outcome trials (42.9 % for SGLT-2 inhibitors, 60% for GLP-1 agonist and 53.8% for DPP-4 inhibitors).6 While the primary outcome was all cause mortality the key secondary outcome was cardiovascular mortality and cardiovascular events.6 The results for the primary and key secondary endpoint are presented in the following table.

Blog Table

The investigators also looked at heart failure events, myocardial infarction (MI)/unstable angina (UA) and stroke. For heart failure events, the authors found SGLT-2 inhibitors were associated with reduced heart failure events compared with all represented groups, GLP-1 agonists were associated with reduced events compared to DPP-4 inhibitors but not with the control group and that DPP-4 inhibitors were not associated with reduced events.6 For the analysis of MI’s and UA, only SGLT-2 inhibitors showed reduced events for total and nonfatal MI compared to control.6 There were no differences between drug classes and no drug class showed reductions in unstable angina.6 Looking at stroke, GLP-1 agonists were associated with reduced nonfatal stroke compared to the control group, however, there were no agents that reduced all stroke events and there were no associated differences between drug classes for nonfatal stroke.6 When the investigators looked at individual drugs within the classes, only empagliflozin, liraglutide and exenatide showed reductions in all-cause mortality.6 The authors concluded overall that the use of SGLT-2 inhibitors or GLP-1 agonists is associated with reduced mortality compared to DPP-4 inhibitors or placebo or no treatment.6

There are obvious limitations with both of these studies, but they lend themselves to promising trends in reduction of cardiovascular events and agents that can serve as important part of our arsenal to treat this disease. Thanks for reading!

References

  1. American Diabetes Association. Cardiovascular disease and risk management: standards of medical care in diabetes-2018. Diabetes Care. 2018; 41(Suppl 1):S86-S104.
  2. Yadlowsky S, Hayward RA, Sussman JB, Mcclelland RL, Min YI, Basu S. Clinical implications of revised pooled cohort equations for estimating atherosclerotic cardiovascular disease risk. Ann Intern Med. 2018; 169(1):20-29.
  3. Gregg EW, Cheng YJ, Srinivasan M, et al. Trends in cause-specific mortality among adults with and without diagnosed diabetes in the USA: an epidemiological analysis of linked national survey and vital statistics data. Lancet. 2018; 391(10138):2430-2440.
  4. Marso S, Daniels G, Brown-Frandsen K, et al. Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2016; 375:311-22.
  5. Zinman B, Wanner C, Lachin JM, et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015; 373:2117-28.
  6. Zheng SL, Roddick AJ, Aghar-jaffar R, et al. Association between use of sodium-glucose cotransporter 2 inhibitors, glucagon-like peptide 1 agonists, and dipeptidyl peptidase 4 inhibitors with all-cause mortality in patients with type 2 diabetes: a systematic review and meta-analysis. JAMA. 2018; 319(15):1580-1591.

 

Perception of failure and its impact on fostering positive change

We all have those patients who seem to understand all of the education provided, recognize the risks of elevated blood sugars, verbalize that this time they will make that one jointly decided upon change, and yet, time after time, they return without making any progress. A recent editorial that I read in JAMA helped me to better understand why these patients may be struggling. (1) I think that many of my patients feel like they have failed when they see elevated A1cs, blood sugar numbers out of range or weight gain. It may be the response to perceived failure that is impeding these patients from achieving their goals.

According to the editorial, people respond to failure on an emotional level and on a cognitive level.(1) In other words, individuals experience feelings about the failure, but also conduct an internal assessment of the cause the failure. Patients who decide that the failure is due to an uncontrollable cause and feel shame are less likely to make changes. Low self-esteem often leads patients along this pathway and patients develop avoidant behaviors to escape these negative feelings.(2)

How can we help?

There are many articles from those in business about how to help someone reset their perception of failure. After all, there are all of those quotes circulating on social media about how founders of companies had hundreds of failures before making their millions. They know about overcoming failure. In a TEDX talk, business person Fred Colantonio talks about how he has learned through his life experiences that failure needs to be reframed as a part of life. (3) Failure is not an absolute. It is a stepping stone and an opportunity to learn and grow.

What this means to me is that these patients can be helped by focusing on the positive instead of the negative. If we can help them see what they have already accomplished instead of what still needs to be fixed this may prevent those feelings of shame that are getting in the way. Also, reframing a perceived failure as just another bump along the road of life that they are capable of impacting may also help. Finally, cheering them on for every small step can help their self-esteem and may help to cement this desired shift in attitude.

S. Mimi Mukherjee, PharmD, CDE, BCPS

References
1. Kangovi S, Asch DA. Behavioral phenotyping in health promotion. JAMA. 2018;319(20):2075-2076.
2. Webb TL. Chang B. Benn Y. “The ostrich problem”:motivated avoidance or rejection of information about goal progress. Soc Personal Psychol Compass. 2013;7(11):794-807.
3. Colantonio, F. How perception of failure affects success. https://www.youtube.com/watch?v=LvXYIKenP4o. Published Jun. 24, 2014. Accessed Jun. 8, 2018.

What in the World?! Meaningful Outcome Measures Beyond HbA1c in Type 1 Diabetes

By a rhetorical raise of hands, how many of us utilize glycated hemoglobin (HbA1c), along with self-monitoring of blood glucose (SMBG), to guide clinical decision-making in the pursuit of glycemic control in our patients with diabetes mellitus (DM)? I would venture to assume that 100% of us would raise our hand as we are devotees of clinical practice guidelines. Second question of the day: how many children and adults with type 1 diabetes mellitus (T1DM) achieve glycemic targets? The correct answer, despite the use of HbA1c and multiple daily SMBGs, only 20% of children and 33% of adults with T1DM achieve HbA1c-driven glycemic targets. Growing evidence of adverse outcomes due to hypoglycemia and suggestion of chronic DM complications as a result of not only sustained hyperglycemia but glycemic variability endorse opportunities for re-defining how we assess efficacy and safety of therapies while in pursuit of glycemic control.1,2  This opportunity requires consideration of the patient’s quality of life, understanding of the dynamic nature of glucose, and the prevention of life-threatening complications due to poor glycemic control.1,2 A Steering Committee – comprised of the American Association of Clinical Endocrinologists, the American Association of Diabetes Educators, the American Diabetes Association, the Endocrine Society, JDRF International, The Leona M. and Harry B. Helmsley Charitable Trust, the Pediatric Endocrine and the T1D Exchange – sought to do just that in expressing that the time is now to optimize utility of new devices that make it feasible to assess the efficacy and safety of antihyperglycemic therapies and technologies beyond HbA1c.1

The described Steering Committee has published a joint consensus statement with the objective to identify and define clinically meaningful outcome measures for patients with T1DM beyond HbA1c.1 As I’m sure we are all well aware, periodic evaluation of HbA1c, as supported by professionally recognized treatment guidelines, is an established surrogate measure in assessing the efficacy and safety of antihyperglycemic therapies and technologies in our T1DM patients.3,4 However, HbA1c is not without its’ shortcomings. The surrogate measure has an inability to capture short-term variations in blood glucose, reflect  the influence of variations in glycosylation, and the impact of variations of glycemic control on patients’ quality of life and incidence of acute events of hypo- and hyperglycemia.1,5  The Steering Committee elaborates that with the technological advances, particularly growing utilization and reliability of CGMs, the stage is primed to pursue utilization of other clinically meaningful outcome measures in clinical practice, research and development of therapies in T1DM.1

The Steering Committee identified the following outcome measure to define – hypoglycemia, hyperglycemia, time in range, diabetic ketoacidosis (DKA), and patient-reported outcomes (PROs). By standardizing the definitions of the listed outcome measures, the committee’s immediate goal is for their use as primary and secondary endpoints in clinical research. This inclusion aims to achieve comprehensive evaluation and understanding of the impact new therapies and technologies have on influencing management of T1DM. Additionally, the utility of these outcome measures in clinical practice are set to empower the clinician to better derive individualized treatment plans for our T1DM patients.

Based on expert opinion and published evidence, the Steering Committee has constructed the following definitions that are clinically meaningful, applicable to nonpregnant patients with T1DM, measurable using existing technologies and applicable regardless of time of day:1

Hypoglycemia:
Level 1 Measurable glucose concentration < 70 mg/dL but ³ 54 mg/dL
Level 2 Glucose < 54 mg/dL
Level 3 Severe event characterized by altered mental and/or physical status requiring assistance
Hyperglycemia:
Level 1 Elevated glucose – glucose > 180 mg/dL and glucose £ 250 mg/dL
Level 2 Very elevated glucose – glucose > 250 mg/dL
Time in Range:
·    Percentage of readings in the range of 70 – 180 mg/dL per unit of time
DKA:
·    Elevated serum or urine ketones (greater than ULN) and serum bicarbonate < 15 mmol/L or blood pH < 7.3
PROs*:
·    Report of the status of a patient’s health condition, health behavior, or experience with healthcare that comes directly from the patient, without interpretation of the patient’s response by a clinician or anyone else.

*as defined by the Food and Drug Administration (FDA) and endorsed by the defined Steering Committee

Although the Steering Committee does not intend for these clinically meaningful outcome measures to replace HbA1c, there is opportunity for these outcomes to augment the limitations of HbA1c. Notably, the standardized definitions of hypoglycemia, hyperglycemia and DKA are coordinated with a previous publication regarding use of CGMs. The advancement and availability of CGM devices are the likely key ingredient to filling the gaps in use of HbA1c alone, as they function to build the bridge to being able to comprehensively capture the efficacy and safety of technologies and antihyperglycemic therapy in clinical research, development and practice.1,6 However, we certainly require a growing body of research to identify the long-term clinical, economic and humanistic impacts directed by the standardization of these clinically meaningful outcome measures. In addition to standardization, it will be of mounting importance for these clinically meaningful outcome measures to be presented in a consistent format and as broadly available to clinicians as HbA1c. While we anticipate more evidence, how do you see your evaluation and management of patients with T1DM being impacted by the standardization and availability of these clinically meaningful outcome measures?

References:

  1. Agiostratidou G, Anhalt H, Ball D, et al. Standardizing clinically meaningful outcome measures beyond HbA1cfor type 1 diabetes: a consensus report of the American Association of Clinical Endocrinologists, the American Association of Diabetes Educators, the American Diabetes Association, the Endocrine Society, JDRF International, The Leona M. and Harry B. Helmsley Charitable Trust, the Pediatric Endocrine Society, and the T1D Exchange. Diabetes Care. 2017; 40(12):1622-30.
  2. Wright L and Hirsch IR. Metrics beyond hemoglobin A1c in diabetes management: time in range, hypoglycemia, and other parameters. Diabetes Technol Ther. 2017;19(Suppl 2):S16-26.
  3. American Association of Clinical Endocrinologists. Treatment of type 1 diabetes. http://outpatient.aace.com/type1-diabetes/treatment (accessed 2018 May 1).
  4. American Diabetes Association. Glycemic targets: standards of medical care in diabetes – 2018. Diabetes Care. 2018;41(Suppl 1):S55-64.
  5. Argento NB, Nakamura K, Sala RD, et al. Hemoglobin A1c, mean glucose, and persistence of glycation ratios in insulin-treated diabetes. Endocr Pract. 2014;20(3):252-60.
  6. Danne T, Nimri R, Battelino T, et al. International consensus on use of continuous glucose monitoring. Diabetes Care. 2017;40(12):1631-40.

Cashing Out on the Sugar Checks?

I know I am not the only one who struggles to get patients with diabetes to check their blood sugars consistently.  As a clinician, studies have revealed to us that self-monitoring of blood glucose (SMBG) reduces Hemoglobin A1c (HbA1c) and improves patients’ blood sugars1,2; however, a recent study revealed that it may no longer be necessary, particularly if the patient is not using insulin.

HbA1c is a standard measurement of glycemic control that is readily available to health care providers for managing diabetes and allows us to confirm home blood sugar readings to ensure proper control.  Historically, we have focused on a target HbA1c of less than 7% in patients with diabetes, while suggesting more lenient goals (< 8%) for patients with complicated cardiovascular disease, short life expectancy, multiple uncontrolled co-morbid disease states, or those at high risk for hypoglycemia. The American College of Physicians (ACP) released new guidelines in March 2018 regarding goals of therapy for patients with diabetes.  ACP suggested clinicians should target HbA1c levels between 7 – 8 percent, rather than 6.5 – 7 percent for patients with diabetes.3  Much controversy exists with this recently released statement from ACP as the American Diabetes Association (ADA) reported that these recommendations were not primarily based upon compelling evidence in trials like ACCORD, ADVANCE, VADT, and UKPDS.  ADA discussed how these trials shaped their recommendations for tighter control, demonstrating decreased microvascular complications and suggested clinicians continue to utilize more stringent goals for most patients with diabetes.4  In addition to the ADA, the American Association of Clinical Endocrinologists (AACE), the American Association for Diabetes Educators (AADE), and the Endocrine Society all strongly disagreed with ACP’s recommendations as well.  So tell me, where do YOU stand on the ACP guideline recommendations for HbA1c??

Part of this control requires patient involvement at home.  In a recent study “Glucose Self-monitoring in Non–Insulin-Treated Patients with Type 2 Diabetes in Primary Care Settings:  A Randomized Trial”, HbA1c was found to be no different in the patients who were checking their blood sugars versus the patients who were not.  Briefly, 450 patients with diabetes (median time of having the disease was 6 years) were randomized to one of three groups:  No Self-Monitoring of Blood Glucose (SMBG), once-daily SMBG, and once-daily SMBG with enhanced patient feedback including automatic tailored messaged delivered via the glucometer.  The outcomes measured were HbA1c levels and health-related quality of life (HRQOL) at 52 weeks.  No significant differences were found in either endpoint, demonstrating that glucose monitoring does not necessarily improve HbA1c, nor did it affect quality of life in this population.5

This study made me think about my own patient population and how I might apply the results.  Some of my patients do a fantastic job monitoring their blood sugars, writing them down, and bringing them to their visits for evaluation—this, of course, makes my job easier.  Other patients struggle to check their blood sugars and rarely do it, often reporting the burden of pricking their fingers and the pain associated with using the lancing device.  This study provided practical application to the latter group and is a patient-centered focused study, which is critical given healthcare’s emphasis on patient-centered care outcomes in recent years.  The evidence allows us to see that some patients may be just fine without checking their sugars regularly but more information is still needed in patients who are insulin dependent. Involving patients in these decisions is crucial because it provides them with a sense of responsibility about their health and wellness but also aids in our ability to see what is going on at home to make better patient-centered clinical decisions.

As an ambulatory care pharmacist who heavily focuses on diabetes management, this study makes me question the need for SMBG for improving outcomes.  When the benefits are lacking, what really is the point?  Checking blood sugars daily can be burdensome, costly, and as shown above, may not improve outcomes. To clarify, I am not suggesting that your patients do not need to be monitoring their blood sugars.  In fact, I still think there are great benefits of SMBG, especially in a new diabetic who is motivated to make lifestyle changes, but that population wasn’t studied in Young et al., and so more research still needs to be completed.  I do see a potential benefit to recommend less SMBG for lowering patient costs if there is no change in HbA1c and HRQOL.  Many of my patients struggle to afford test strips, particularly those who do not have proper coverage.  Additionally, many of my patients are on a strict budget and have trouble affording food, not to mention “healthy food” that will better control their blood sugars.  Based on this information, I am suggesting that patients be part of the plan, and that as health care providers, we discuss the needs of our patients, the goals of therapy, and design a plan that is specific to each individual we are treating.  More evidence is still needed, but less SMBG is certainly something I have introduced to my practice and will continue to work with my patients individually to set realistic expectations about their diabetes control.

Personally, I believe SMBG is appropriate in some circumstances but may not be helpful in others.  Each individual patient requires a different goal and we should be utilizing guidelines for what they actually are:  “Guidelines”.  Diabetes is a very individualized disease state that often leads to many other conditions, and proper control along with different medication therapies have demonstrated positive outcomes related to both micro- and macro-vascular complications.  So my question to you as a practicing clinician:  Do YOU see any value in SMBG?  If so, how do YOU use it in your diabetic non-insulin dependent patient population?

Written by:  Nicole Slater, PharmD, BCACP

References

  1. Polonsky WH, Fisher L, Schikman CH, et al. Structured self-monitoring of blood glucose significantly reduces A1C levels in poorly controlled, noninsulin-treated type 2 diabetes: results from the Structured Testing Program study. Diabetes Care 2011;34:262–267
  2. Schwedes U, Siebolds M, Mertes G, et al. Meal-Related Structured Self-Monitoring of Blood Glucose:  Effect on diabetes control in non-insulin treated type 2 diabetic patients.  Diabetes Care 25:1928-1932.
  3. Qaseem A, Wilt TJ, Kansagara D, et al. Hemoglobin A1c Targets for Glycemic Control with Pharmacologic Therapy for Nonpregnant Adults with Type 2 Diabetes Mellitus:  A Guidance Statement Update from the American College of Physicians.  Ann Intern Med 2018.  Available from:  http://annals.org/aim/fullarticle/2674121/hemoglobin-1c-targets-glycemic-control-pharmacologic-therapy-nonpregnant-adults-type.  Accessed 5 April 2018.
  4. Glycemic Targets:  Standards of Medical Care in Diabetes-2018.  American Diabetes Association.  Diabetes Care 2018;41(Supplement 1):S55-S64.  Available from:  http://care.diabetesjournals.org/content/41/Supplement_1/S55.  Accessed 4 April 2018.
  5. Young LA, Buse JB, Weaver MA. Glucose Self-monitoring in Non–Insulin-Treated Patients With Type 2 Diabetes in Primary Care Settings:  A Randomized Trial.  JAMA 2017;177(7):920-929.

 

SGLT-2 Inhibitors for Type 1 Diabetes: A Worthwhile Gamble?

SGLT-2 inhibitors continue to be studied in type 1 diabetes despite the FDA warning about euglycemic diabetic ketoacidosis (DKA) and knowing that patients with type 1 diabetes are at increased risk of DKA compared to their type 2 counterparts. 1 Perhaps, it’s because of the blood pressure lowering, weight loss, and positive cardiovascular outcomes observed in type 2 diabetes. It sure would be exciting if these drugs could be viable options for patients with type 1 diabetes.

So, what does the literature say? The DEPICT-12 trial was a double-blind, randomized, parallel-controlled, study that included patients with uncontrolled type 1 diabetes. Patients were randomly assigned to dapagliflozin 5 mg or 10 mg once daily or placebo. The primary outcome was change in A1C after 24 weeks. In total, 833 patients were included: mean baseline A1C=8.53%, mean BMI=28kg/m2. At week 24, both doses of dapagliflozin significantly reduced A1C compared with placebo (mean difference from baseline to week 24 for dapagliflozin 5 mg vs placebo was −0.42% [95% CI −0.56 to −0.28; p<0.0001] and for dapagliflozin 10 mg vs placebo was −0.45% [−0.58 to −0.31; p<0.0001]). Rates of hypoglycemia and DKA were similar between groups. The authors concluded that dapagliflozin is a promising adjunct treatment to insulin to improve glycemic control in patients with inadequately controlled type 1 diabetes. It’s important to note that the study design limited insulin reduction to 20% based on previous studies to limit DKA events.3 It seemed to work in this case!

 

The newest SGLT2 inhibitor to be explored is sotagliflozin which is actually a dual SGLT1 and SGLT2 inhibitor. SGLT1 has additional effects on the proximal intestine and by inhibiting SGLT1, there is reduced glucose absorption which improves postprandial hyperglycemia. In a phase III, double-blind, randomized, controlled trial (InTandem3)4, 1402 patients with type 1 diabetes were randomized to sotagliflozin 400mg/day or placebo for 24 weeks. Baseline characteristics include mean BMI of 28kg/m2 and 71% of patients with BMI≥25 kg/m2. Mean insulin doses were 56-58 units/day and mean A1C was 8.2%. Significantly more patients in the sotagliflozin group compared to placebo achieved A1C lower than 7% (207 patients [29.6%] vs. 111 [15.8%]). The A1C reduction from baseline to week 24 was significantly greater in the sotagliflozin group (difference, −0.46%; P<0.001). There was also greater weight loss with sotagliflozin (difference=−2.98 kg; P<0.001). In the sotagliflozin group, the placebo-corrected reductions from baseline in the mean daily total, bolus, and basal doses of insulin were −5.3 units per day (−9.7%), −2.8 units per day (−12.3%), and −2.6 units per day (−9.9%), respectively (P <0.001 for all comparisons). Overall, rates of hypoglycemia were similar between groups. Diarrhea (4.1% vs 2.3%) and genital mycotic infections (6.4% vs 2.1%) were more common with sotagliflozin compared with placebo, respectively.  The rate of acidosis-related adverse events was 8.6% in the sotagliflozin group and 2.4% in the placebo group with actual DKA occurring in 3.0% in the placebo group and 0.6% in the placebo and more cases in those on insulin pumps.

The clinical efficacy is quite remarkable, but the increase risk of DKA is concerning, especially because the trial included a higher level of education and monitoring for DKA than what occurs in most usual clinical practice. Sotagliflozin is also most similar structurally to canagliflozin, and although bone loss and amputations have not been seen with sotagliflozin, we lack long term outcomes.5

A meta-analysis by Chen and colleagues6, reviewed over 11 trials and 581 patients, assessed the safety and efficacy of SGLT2 inhibitors vs. placebo in those with T1DM who were on insulin. The mean baseline characteristics included age of 41, duration of diabetes 21.28 years, A1C 8.026%, and BMI 27.25 kg/m2 . Hemoglobin A1C  was reduced by 0.37% and total body weight was reduced by 2.54kg,  Total adverse effects were similar between groups,  but not surprisingly, there was an increase in DKA in those on SGLT2 inhibitors.

Overall, SGLT-2 inhibitors show promise in type 1 diabetes for weight control and A1C lowering. Based on EMPA-REG and CANVAS, they may even have potential to improve cardiovascular outcome as seen in patients with type 2 diabetes. Perhaps, if we follow the rule in the DEPICT-1 dapagliflozin trial and limit insulin reduction to no more than 20%, we can prevent DKA from occurring?

What do you think? Is the benefit worth the risk? This is such a difficult population to achieve A1C goal, which is often plagued by hypoglycemia and unpredictable hyperglycemia and hypoglycemia. (See Adam Brown’s 42 factors that can impact BG7) . It would be nice to have another tool to treat these patients. Yet, DKA can be life threatening and is it worth the gamble even if the overall rates are low?  It reminds me a bit of Russian roulette. Is it just bound to happen if we use these agents enough?

Then again, maybe one day, insulin pump technology will advance that every patient will have an artificial pancreas. But until that day comes, it sure would be nice to have another medication to use in this difficult to treat population.

 

  1. FDA Drug Safety Communication. Available at: https://www.fda.gov/drugs/drugsafety/ucm475463.htm. Accessed 3/18/18.
  2. Dandona P, Mathieu C, Phillip M, et al. Efficacy and safety of dapagliflozin in patients with inadequately controlled type 1 diabetes (DEPICT-1): 24 week results from a multicentre, double-blind, phase 3, randomised controlled trial. Lancet Diabetes Endocrinol. 2017;8587(17):1-13. doi:10.1016/S2213-8587(17)30308-X.
  3. Henry RR, Rosenstock J, Edelman S, et al. Exploring the potential of the SGLT2 inhibitor dapaglif lozin in type 1 diabetes: A randomized, double-blind, placebo-controlled pilot study. Diabetes Care. 2015;38(3):412-419. doi:10.2337/dc13-2955.
  4. Garg SK, Henry RR, Banks P, et al. Effects of Sotagliflozin Added to Insulin in Patients with Type 1 Diabetes. N Engl J Med. 2017:NEJMoa1708337. doi:10.1056/NEJMoa1708337.
  5. Rendell MS. Efficacy and safety of sotagliflozin in treating diabetes type 1. Expert Opin Pharmacother. 2017;0(0):14656566.2017.1414801. doi:10.1080/14656566.2017.1414801.
  6. Chen J, Fan F, Wang JY, et al. The efficacy and safety of SGLT2 inhibitors for adjunctive treatment of type 1 diabetes: A systematic review and meta-analysis. Sci Rep. 2017;7(March):1-9. doi:10.1038/srep44128.
  7. Factors Affect BG Control. Diatribe. Available at: https://diatribe.org/42factors. Accessed 3/18/18.

Written by: Diana Isaacs, PharmD, BCPS, BC-ADM, CDE, Clinical Pharmacy Specialist, Cleveland Clinic Diabetes Center