GSHP Newsletter
GSHP 2019  Spring Meeting  
March 8-10, 2019
Marriott Riverfront
Savannah, GA 
 
GSHP thanks our 215 attendees, speakers and poster presenters for making this year's meeting a tremendous success.   

From ASHP
 
Practice Advancement Initiative Looks to Next Decade
As the ASHP Practice Advancement Initiative (PAI) nears its tenth year, pharmacy leaders from across the nation are helping to shape the initiative to advance pharmacy practice in ambulatory and acute care settings over the next decade.
The 15-member PAI 2030 advisory panel convened at ASHP's Bethesda, Md., headquarters March 11-12 to review PAI's initial recommendations and suggest improvements and new areas of emphasis.
Topics under discussion included the use of healthcare analytics data to inform decision-making, the use of emerging technologies for patient monitoring and drug delivery, how artificial intelligence may affect care delivery, and support for advanced roles for pharmacy technicians.
"This was a difficult task but a great opportunity," Douglas J. Scheckelhoff, Senior Vice President of ASHP's Office of Practice Advancement, said of the committee's deliberations. He called the advisory meeting "the first step in the process of setting the future course of this highly successful initiative."
The panel's recommendations will be reviewed by ASHP's leadership, members, and other stakeholders. The final PAI revisions are scheduled to be unveiled at ASHP's 2019 Midyear Clinical Meeting in Las Vegas.
PAI was launched in 2010 and was initially called the Pharmacy Practice Model Initiative (PPMI). AJHP reported in 2011 that the initiative's goal was "to significantly advance the health and well-being of patients in hospitals and health systems by developing and disseminating optimal pharmacy practice models that are based on the effective use of pharmacists as direct patient care providers."
PPMI and the recommendations from the 2014 Ambulatory Care Conference and Summit were collectively rebranded as PAI in 2015 to better align with the profession's emphasis on clinical activities, including expanded roles in acute and ambulatory care settings and transitional care services.
PAI provides benchmarks and self-assessment tools that pharmacy departments and practitioners can use to identify gaps and areas for improvement. The initiative emphasizes the importance of leadership and accountability at all levels to help the pharmacy profession realize its full potential in the changing healthcare environment.
Scheckelhoff said PAI has advanced the role of the pharmacist in ambulatory clinics, emergency departments, and transitional care activities.
He said the initiative also supports the expansion of clinical and leadership roles for pharmacists, such as involvement in drug therapy using pharmacogenomics, increased accountability through credentialing and linkage of pharmacy services to patient care outcomes, and the identification of new areas for medication stewardship.
National data from PAI self-assessments indicate areas where pharmacy departments have been especially successful in establishing practices described in PAI.
In 2017, more than 90 percent of pharmacy departments that submitted PAI data reported that pharmacists had leadership roles in antimicrobial stewardship programs. More than 90 percent of pharmacy departments also reported that they had implemented established criteria to identify problematic and high-risk drug therapies.
Areas for improvement included hospitals' adoption of collaborative practice agreements between pharmacists and other healthcare providers and the examination of ways to improve the effectiveness of institutional accountable care organizations. Less than half of self-assessment respondents reported implementing these progress measures in 2017.
AJHP  has published multiple reports describing how pharmacy departments have used PAI's tools to reshape pharmacy practice. Recent examples include:
  • Via Christi Health used PAI's framework to shift several Kansas hospitals from a staff-specialist practice model to a team-based model to improve the consistency of care and support staff retention and scheduling flexibility.
  • Surrey Memorial Hospital in British Columbia, Canada, implemented PAI to expand pharmacy technicians' roles and responsibilities to include medication order entry, verification, and final checking without routine direct supervision by a pharmacist. As a result, pharmacists were able to expand their direct patient-care and medication therapy management activities.
  • The University of Texas MD Anderson Cancer Center received a PAI grant from the ASHP Foundation to develop and implement a pharmacy-driven transitional care program that expands clinical roles for pharmacists.
  • Henry Ford Hospital in Detroit, Michigan, used PAI's Ambulatory Care Self-Assessment Tool to study its hospital-based clinics and identify opportunities to standardize best practices for ambulatory-care pharmacy services.
Eric Maroyka, Director of ASHP's Center on Pharmacy Practice Advancement, said PAI 2030's revised framework will continue to provide tools, networking opportunities, and expertise that promote practice advancement across all settings of care.
Maroyka said the participation of state affiliates in PAI activities has helped to spur growth and uptake of the initiative and its concepts. He also noted that local PAI activities have led to advocacy efforts that support the provision of optimal pharmacy services.
 


FREE CE for GSHP Members!  
 
Webinar-Thursday, April 11, 2019 - 12 noon-1:00 pm
New Therapies in Rheumatology: Focus on JAK inhibitors
 
Pharmacist Learning Objectives
By the end of this program the learner will be able to:
*       Describe the epidemiology, risk factors, and pathophysiology associated with rheumatoid arthritis (RA)
*       Discuss FDA-approved treatment options for RA
*       Identify patient-specific considerations and monitoring parameters when initiating JAK inhibitor therapy
*       Evaluate evidence-based literature for use of JAK inhibitor therapy in patients with RA
 
Pharmacy Technician Learning Objectives
By the end of this program the learner will be able to:
*       Describe the epidemiology, risk factors, and pathophysiology associated with rheumatoid arthritis (RA)
*       List FDA-approved treatment options for RA
*       List patient-specific considerations and monitoring parameters when initiating JAK inhibitor therapy
 
Colleen McCabe, PharmD
PGY1 Specialty Pharmacy Resident
Emory University Hospital Midtown (EUHM)
 
Georgia Society of Health-System Pharmacists is accredited by the Accreditation Council for Pharmacy Educ
ation (ACPE) as a provider of continuing pharmacy education. Participants of the session who complete the evaluation and provide accurate NABP e-Profile information will have their credit for 1.0 contact hours (0.10 CEU) submitted to CPE Monitor as early as 14 days after the event and no later than 60 days after the event. Please know that if accurate e-Profile information is not provided within 50 days of the event, credit cannot be claimed after that time. The participant is accountable for verifying the accurate posting of CE credit to their CPE Monitor account within 60 days.
UAN # 0228-0000-19-035-L01-P; 0228-0000-19-035-L01-T
 
This is a member service of GSHP.  There is no charge for members to attend.   Dues must be current to receive CE credit.
Non-members will be charged $20.
 
Non-member registration:
 

Members in Motion

The Communications Committee has developed a Members in Motion column for the newsletter.
 
The purpose
of the column is to recognize members who have received an award, presented at a meeting, elected to an office or some other practice achievement.
 
Here is the Members in Motion submission link:
 
Please bookmark it and use as needed to help us identify members to recognize.

PTCB Certification Eligibility Requirements To Change in 2020

Education/Training Programs Can Apply Now for PTCB Recognition

 
WASHINGTON, DC -- Starting in 2020, PTCB, the nation's leading certifying organization for pharmacy technicians, will change its eligibility requirements for the Certified Pharmacy Technician (CPhT) Program and update its Pharmacy Technician Certification Exam (PTCE). PTCB will offer two eligibility pathways for technicians submitting certification applications beginning January 1, 2020. One will be completion of a PTCB-recognized education/training program, and the other will be equivalent work experience. 

Announced in January 2018, these changes are based on data PTCB collected via Job Task Analysis survey responses from more than 40,000 pharmacy technicians and comments from the pharmacy community, including technician employers and educators, state and national pharmacy associations, and state boards of pharmacy. 

"PTCB relies on data and pharmacy stakeholder conversations in all we do with the goal of advancing medication safety," said William Schimmel, PTCB Executive Director and CEO. "The new eligibility requirements are based on input from pharmacy professionals that certain knowledge, skills, and abilities are acquired most effectively through education/training or work experience. Pharmacy employers can be confident that PTCB-certified pharmacy technicians have demonstrated they have the knowledge to advance patient care in today's pharmacy," Schimmel said. 

Education/Training Program Recognition
In preparation for 2020, PTCB has launched an application process for education/training programs to become PTCB-recognized by attesting that their curriculum meets specified knowledge requirements. The process requires directors of education/training programs not accredited by the American Society of Health-System Pharmacists/Accreditation Council for Pharmacy Education (ASHP/ACPE) and/or by the Accrediting Bureau of Health Education Schools (ABHES) to submit attestation. 

Programs that are ASHP/ACPE and ABHES-accredited are recognized as fulfilling PTCB's curriculum requirements and are not required to attest. More than 600 programs have become recognized to date. "Our recognition process for education/training programs lays the foundation for implementing significant changes in CPhT eligibility requirements along with updates to the PTCE," said Schimmel. 

New Eligibility Requirements
Students who complete a PTCB-recognized education/training program will be eligible to apply for, and earn, their CPhT credential starting in 2020. As an alternative, PTCB will offer a second eligibility pathway based on work experience for technicians who have completed 500 work hours and attest to fulfilling specified knowledge requirements. "While PTCB values education as a key component to earning certification, we also recognize the merit of work experience," Schimmel said. "This pathway means technicians who've worked extensively in the field, but haven't been in a position to complete PTCB-recognized education can still pursue our national certification." 

"Aspiring CPhTs must show they have the necessary knowledge and skills to do their jobs safely and effectively," said PTCB Certification Council President Kilee Yarosh, RPh, Market Director of Pharmacy Steward Healthcare, Warren OH. "PTCB's eligibility requirements in 2020 go beyond high school and ensure those seeking to earn their certification are qualified and can successfully demonstrate competence."

Exam (PTCE) Updates
Beginning January 1, 2020, PTCE content will be organized into four knowledge areas rather than the current nine, and will focus only on essential knowledge that applies across practice settings. Consistent with industry best practices and accreditation standards, PTCB periodically conducts a Job Task Analysis study approximately every 5 years as the foundation for its national certification program. "The data from PTCB's study in 2016 informed the updates to be made in 2020, and reflect technician responsibilities in current pharmacy practice," said Levi Boren, PhD, PTCB Senior Director of Certification Programs. PTCB also received more than 500 individual comments during a 90-day comment period on implementation of the education/training eligibility pathway. "PTCB listens to the pharmacy community. Our comment period allowed us to collect valuable feedback," Boren added.

"PTCB's research-based changes are critical for keeping PTCB's CPhT Program up to date on pharmacy practice and the vital role of pharmacy technicians," added Barbara Limburg, PharmD, PTCE Exam Development Committee Chair and former sterile compounding professor of pharmacy technicians at South Suburban College and Associate Professor at Chicago State University College of Pharmacy. 

More information is available on PTCB's website, including the listing of PTCB-recognized education/training programs, program recognition attestation form, and updated PTCE content blueprint.


GSHP Leadership Profile
Jessica Hicks 
What is your current leadership position in GSHP?
 
I am the Northeast Metro District Director-elect.
 
 
What benefits do you see in being active in a professional association such as GSHP?  
 
I love the variety of educational programming offered by GSHP, whether it be at a state-wide meeting, local district dinner meeting, or webinar. There is always an avenue for people to get plugged in and stay up to date on the latest things happening in pharmacy.
 
I also greatly enjoy the networking opportunities and have been able to meet so many amazing people! It's so great to have such a large group of colleagues with whom I can share ideas and ask for advice.
 
 
What initially motivated you to get involved in GSHP?
 
I was a student member of GSHP while I was in pharmacy school and was interested in getting more involved in my profession at a local and state level. Once I moved back to Georgia after residency and started working at Emory Midtown, I was encouraged to rejoin by our current GSHP president, Collin Lee. I greatly enjoy our local district meetings, not just for the food or CE, but because they are an excellent to network and meet others in our profession. I have made many friends that I have ended up running into at both local and state GSHP meetings.
 
 
Where did you go to pharmacy school?
 
I attended Mercer University College of Pharmacy.
 
 
Where have you trained or worked?  
 
I completed my PGY1 residency at Erlanger Health System in Chattanooga, Tennessee.
 
 
Describe your current area of practice and practice setting:
 
I am currently a Clinical Pharmacist at Emory University Hospital Midtown, working primarily with our cardiothoracic surgery and ENT patient populations. I also am the co-coordinator for the advanced institution APPE students that rotate through our facility.
 
What advice would you give to student pharmacists?
 
One of the things I tell every student who is on rotation with me is to never close yourself off to new experiences. Some students may know exactly which area of pharmacy they want to practice upon graduation, and that is a great thing! However, just because you already know doesn't mean you won't find a new area of practice that may surprise you.
 
 
What pharmacy related issues keep you up at night?
 
Nothing really comes to mind. I try very hard to maintain a strong work/life balance.
 
 
Do you have any special interests or hobbies outside of work?
 
I'm a huge sports fan, so I love going to live sporting events, particularly the Atlanta Braves, Atlanta United, and Tennessee Volunteers.
 
What is your favorite place to vacation?
 
I don't necessarily have a favorite spot, but would prefer to get to a destination on a cruise ship!
 
What 3 adjectives would people use to best describe you?
 
Determined, loyal, and dependable.

Clinical Articles
Aspirin for Primary Prevention - Beneficial or Harmful?
 
Authors: Mary Bailey Jones, Pharm.D. Candidate Class of 2019, Sarah Hall, Pharm.D. Candidate Class of 2020, Maria Miller Thurston, Pharm.D., BCPS
 
Mercer University College of Pharmacy
 
Corresponding Author:
Maria Miller Thurston, Pharm.D., BCPS
Clinical Associate Professor
3001 Mercer University Drive
Atlanta, GA 30341
T: (678) 547-6253
F: (678) 547-6384
 
 
Background
In 2015, cardiovascular disease was the leading cause of death in the United States of America for both men and women.1 Aspirin's role in the setting of primary cardiovascular disease prevention is related to its ability to inhibit platelet aggregation. This inhibition prevents the accumulation of blood clots that form as a result of reduced blood flow around atherosclerotic plaques, thus resulting in increased blood flow to and decreased rates of hypoxic damage to the cranial and myocardial tissues.2 Two meta analyses, both with study populations of individuals without clinical cardiovascular disease, demonstrated that aspirin decreased the risk of major cardiovascular disease. More specifically, one these meta analyses revealed different benefits depending on gender, where women using aspirin therapy had a reduction of ischemic stroke while men had decreased rates of myocardial infarction (MI).3,4 The results of the Women's Health Study, which included healthy women over the age of 45, demonstrated that aspirin lowered the risk of ischemic stroke, increased the risk of hemorrhagic stroke, and showed no significant risk reduction in major cardiovascular events.5 In a third meta-analysis of randomized controlled trials, long-term aspirin use reduced all-cause mortality, ischemic stroke, but did not reduce the risk of cardiovascular mortality.6
 
The United States Preventative Services Task Force (USPSTF) identifies primary risk factors for cardiovascular disease as older age, male sex, abnormal lipid levels, hypertension, diabetes mellitus and smoking tobacco.7 In 2016, the USPSTF issued their current recommendations for aspirin-use in the setting of prevention of cardiovascular disease and colorectal cancer. They recommend that aspirin be initiated for primary prevention in adult patients between the ages of 50 to 59 years who have a greater than or equal to a 10% 10-year atherosclerotic cardiovascular disease (ASCVD) risk. They also warrant caution with the use of aspirin in adult patients over the age of 60 years who have a greater than or equal to a 10% 10-year ASCVD risk, leaving the decision ultimately up to the clinician's discretion.7 The USPSTF based their recommendations off of adequate evidence that demonstrated the reduction of cardiovascular events and recommends the aforementioned items with moderate certainty.7
 
While previous studies have proven aspirin to be effective in primary prevention for certain cardiovascular events, such as MI and some strokes, USPSTF recommendations remind clinicians to weigh risk versus benefits due to the potential for increased risk of bleeding that is associated aspirin therapy. Aspirin has FDA-labeled indications for prophylaxis in MIs, transient ischemic attacks and cerebrovascular accidents.8,9 However, recent studies have demonstrated non-significant reduction in cardiovascular outcomes when aspirin is used in the setting of primary prevention.
 
 
Recent Evidence Regarding Aspirin for Primary Prevention
"Effects of Aspirin for Primary Prevention in Persons with Diabetes Mellitus" (ASCEND Trial)
The ASCEND trial aimed to assess efficacy and safety of enteric coated aspirin (100 mg daily), as compared to placebo, in diabetic individuals without cardiovascular disease at randomization. The primary endpoint was defined as the first serious vascular event, defined as a composite of nonfatal MI, nonfatal stroke, (excluding confirmed intracranial hemorrhage) or transient ischemic stroke or death from any vascular cause (excluding confirmed intracranial hemorrhage).  Patients received 100 mg daily aspirin versus matching placebo. The primary efficacy outcome occurred in a statistically significant lower percentage of patients in the aspirin group as compared to the placebo group (658 [8.5%] vs. 743 [9.6%]; rate ratio, 0.88; 95% CI, 0.79 to 0.97; P=0.01). Participants receiving daily aspirin for primary prevention experienced a 12% lower risk of serious cardiovascular events compared to the placebo group. However, the risk of major bleeding events from aspirin was 29% higher than with placebo.10
 
"Use of Aspirin to Reduce Risk of Initial Vascular Events in Patients at Moderate Risk of Cardiovascular Disease" (ARRIVE Trial)
The ARRIVE trial aimed to assess both efficacy and safety of aspirin in the setting of primary prevention in adult patients with moderate risk for cardiovascular disease. The primary endpoint was the composite outcome of time to first occurrence of cardiovascular death, MI, unstable angina, stroke or transient ischemic attack.  In this randomized, double-blind, placebo-controlled trial participants received enteric-coated aspirin 100 mg daily or placebo. The primary efficacy endpoint occurred in 269 (4.29%) of 6270 patients in the aspirin group and 281 (4.48%) of 6276 patients in the placebo group (HR 0.96, 95% CI 0.81 - 1.13, p = 0.6038). Gastrointestinal bleeding events (mild) occurred in 61 (0.97%) patients in aspirin group versus 29 (0.46%) in placebo group (HR 2.11, 95% CI 1.36-3.28, p =0.0007). Overall, the trial failed to demonstrate a significant benefit associated with aspirin's role in primary prevention.11
 
"Effect of Aspirin on Cardiovascular Events and Bleeding in the Healthy Elderly" (ASPREE Trial)
The ASPREE trial was conducted to assess the safety and efficacy of aspirin for primary prevention in elderly patients. The primary endpoint was the composite of death, dementia or persistent physical disability. Participants received enteric-coated aspirin 100 mg daily or placebo. There was no significant benefit associated in aspirin therapy with cardiovascular outcomes in healthy elderly adults (HR 0.95, 0.83-1.03, p>0.05) but the rates of major bleeding remained high. In this study, aspirin for primary prevention did not prolong disability-free survival among the elderly.12
 
 
Moving Forward - Is Aspirin of the Past?
Based on the results of the literature presented above, the benefit of aspirin in the setting of primary prevention continues to remain relatively unclear. While previous studies have demonstrated some benefit in the reduction of ischemic stroke in women and MI in men, not all studies offer strong and clear cut data supporting these outcomes.3,4,5 However, the common thread with most of the literature remains constant, which involves the increased risk for major bleeding and hemorrhagic stroke associated with aspirin use.
 
In a recent opinion article published in the National Institute of Health Director's Blog, Dr. Francis Collins stated that the age-old concept of aspirin use for primary prevention might prove to be more harmful than helpful.13 In another article written by the editor in chief of the Harvard Heart Letter, Dr. Deepak Bhatt reminds his audience that aspirin has yet to gain a FDA labeled indication for use in primary prevention.14 He also makes the bold statement that others seem unwilling to say so candidly, " however, in the absence of diabetes, most otherwise healthy people should probably not be taking a daily aspirin to prevent heart attacks."14 Dr. Bhatt continues to echo the USPSTF recommendations that the decision to begin aspirin therapy for primary prevention should be one that is made with your physician and highly individualized.15 Considering the ARRIVE trial's results, he also encourages patients that are already taking aspirin for primary prevention to meet with their physician to discuss if they should continue therapy.15
 
Considering these results and in light of recently published literature, it is reasonable to assume that the USPSTF recommendations will remain the same in the time being. While there is now an added benefit of clinical trials involving a more diverse patient population in the regards to gender, age, and specific medical conditions, the outcomes do not provide us with the luxury of a clear answer. Echoing the current USPSTF recommendations, it is important to weigh risk versus benefit in our patients when deciding the initiation of prophylactic aspirin therapy. Pharmacists can play an integral role in assessing appropriateness of aspirin therapy and serving as a key resource for clinicians when determining therapy initiation or continuation. Pharmacists can provide necessary medication counseling and education to patients regarding aspirin therapy as well as assist physicians in monitoring bleeding episodes and other potential adverse drug reactions.
 
References
1 . FastStats. CDC.gov. https://www.cdc.gov/nchs/fastats/leading-causes-of-death.htm. Published 2018. Accessed September 10, 2018.
2. Aspirin Use for the Primary Prevention of Cardiovascular Disease and Colorectal Cancer: Recommendation Statement. Aafp.org. https://www.aafp.org/afp/2016/1015/od1.html. Published 2018. Accessed September 18, 2018.
3. Aspirin for the Primary Prevention of Cardiovascular Events in Women and Men: A Sex-Specific Meta-Analysis of Randomized Controlled Trials. JAMA. 2006;295(3):306-314.
4. Berger J, Lala A, Krantz M, Baker G, Hiatt W. Aspirin for the prevention of cardiovascular events in patients without clinical cardiovascular disease: A meta-analysis of randomized trials. Am Heart J. 2014;162(1):115-124.e2. doi:10.1016/j.ahj.2011.04.006.
5. Ridker P, Cook N, Lee I. A randomized trial of low-dose aspirin in the primary prevention of cardiovascular disease in women. New England Journal of Medicine. 2005;352(13):1293-1304. doi:10.1016/j.jvs.2005.04.009.
6. Raju N, Sobieraj-Teague M, Hirsh J, O'Donnell M, Eikelboom J. Effect of Aspirin on Mortality in the Primary Prevention of Cardiovascular Disease. Am J Med. 2011;124(7):621-629. doi:10.1016/j.amjmed.2011.01.018.
7. Final Recommendation Statement: Aspirin Use to Prevent Cardiovascular Disease and Colorectal Cancer: Preventive Medication - US Preventive Services Task Force. Uspreventiveservicestaskforce.org. https://www.uspreventiveservicestaskforce.org/Page/Document/RecommendationStatementFinal/aspirin-to-prevent-cardiovascular-disease-and-cancer. Published 2018. Accessed September 10, 2018.
8. Aspirin. Lexi-Drugs. Lexicomp Online. https://online.lexi.com. Hudson, OH: Lexi-Comp, Inc; 2018. Accessed September 15, 2018.
9. Aspirin. Consumer Drug Information. Micromedex 2.0. https://micromedexsolutions.com/.Greenwood Village, CO; Truven Health Analytics; 2018. Accessed September 15, 2018.
10. The ASCEND Study Collaborative Group. (2018) Effects of Aspirin for Primary Prevention in Persons with Diabetes Mellitus. N Engl J Med doi:10.1056/nejmoa1804988.
11. Gaziano J, Brotons C, Coppolecchia R et al. (2018) Use of aspirin to reduce risk of initial vascular events in patients at moderate risk of cardiovascular disease (ARRIVE): a randomised, double-blind, placebo-controlled trial. Lancet doi:10.1016/s0140-6736(18)31924-x.
12. McNeil JJ, Wolfe R, Tonkin AM et al. (2018) Effect of Aspirin on Cardiovascular Events and Bleeding in the Healthy Elderly. N Engl J Med doi: 0.1056/NEJMoa1805819
13. Collins D. An Aspirin a Day for Older People Doesn't Prolong Healthy Lifespan. NIH Director's Blog. https://directorsblog.nih.gov/2018/09/25/an-aspirin-a-day-for-older-people-doesnt-prolong-healthy-lifespan/. Published 2018. Accessed September 26, 2018.
14. Deepak Bhatt M. Aspirin for primary prevention of cardiovascular disease? - Harvard Health Blog. Harvard Health Blog. https://www.health.harvard.edu/blog/aspirin-for-primary-prevention-of-cardiovascular-disease-2018092014858. Published 2018. Accessed September 26, 2018.
15. Deepak Bhatt M. Aspirin for primary prevention of cardiovascular disease, part 2 - Harvard Health Blog. Harvard Health Blog. https://www.health.harvard.edu/blog/aspirin-for-primary-prevention-of-cardiovascular-disease-part-2-2018092514890. Published 2018. Accessed September 26, 2018.
 

Metformin Use in Patients with Reduced Kidney Function
Authors: Rick Hessler, Pharm.D.* and Kendra Manigault, PharmD., BCPS, BCACP, CDE
*pharmacy student at the time of writing
 
Mercer University College of Pharmacy
Corresponding author:
Kendra Manigault, Pharm.D., BCPS, BCACP, CDE
Clinical Assistant Professor
 
Type 2 diabetes mellitus (T2DM) is characterized by dysfunction of the insulin-producing beta cells in the pancreas as well as reduced insulin sensitivity. These factors contribute to an overall presentation of impaired carbohydrate and fat metabolism leading to symptoms such as pronounced hyperglycemia, polyphagia, polyuria, polydipsia, and/or blurry vision.1 Uncontrolled T2DM may lead to serious complications such as retinopathy, neuropathy, and increased risk for heart disease.2 According to a 2014 report from the Centers for Disease Control and Prevention, 9.3% or over 29 million Americans have diabetes. The report stated that patients with diabetes have 1.7 times the risk for death related to cardiovascular disease. It was also found that from 2005-2008, 4.4% of patients over 40 years of age with diabetes had advanced diabetic retinopathy which can lead to serious loss of vision. Additionally, the report found that in 2011, diabetes was the cause of 44% of new kidney failure cases.3
Although some patients can manage their diabetes with lifestyle and diet changes, others must use medications. Biguanides lower blood glucose levels by decreasing hepatic glucose production, decreasing intestinal absorption of glucose, and improving insulin sensitivity. Phenformin, a biguanide approved by the FDA in 1959, was withdrawn from the market in the late 1970s due to a strong association between its use and lactic acidosis.4 Lactic acidosis occurs due to disruption of normal glucose metabolism leading to excess lactic acid production and a failure of the body's buffering systems.5 It most commonly occurs in patients with some degree of renal insufficiency.Complications of lactic acidosis include hypothermia, hypotension, resistant bradyarrhythmias, and death.6
Metformin, another biguanide, was approved in some developed countries as early as the 1970s; however, metformin was not approved in the United States until 1995 likely due to lingering suspicions surrounding the lactic acidosis associated with its predecessor phenformin.7 It is first line therapy for most patients with T2DM according to the American Diabetes Association (ADA).8 Common side effects of include diarrhea, nausea and upset stomach. Lactic acidosis rarely occurs with a reported incidence of 0.03 cases per 1,000 patient years.6 Additionally, it has been reported that the incidence of lactic acidosis with metformin is 20 times less than phenformin.9 Initially, guidance limited use of metformin in male patients with serum creatinine ≥1.5 mg/dL and in female patients ≥1.4 mg/dL.6 Through the years, metformin has been proven to be safe and effective in many large studies which led to multiple petitions to modify serum creatinine restrictions.7 As a result, the FDA reassessed the safety of metformin by reviewing several studies from the medical literature. It was determined that metformin was safe in patients with mild to moderate renal impairment.10 As such, the FDA updated guidance for use of metformin. This guidance utilizes patient's estimated glomerular filtration rate (eGFR) instead of serum creatinine because it provides a better estimate of kidney function in patients with kidney disease. 10
Table 110
-Baseline eGFR should be obtained before initiating metformin
-Monitor eGFR at least annually. More frequently in patients at increased risk to develop renal impairment such as the elderly
- Discontinue metformin at the time of or before an iodinated contrast imaging procedure in patients with an eGFR between 30 and 60 mL/minute/1.73 m2; in patients with a history of liver disease, alcoholism, or heart failure; or in patients who will be administered intra-arterial iodinated contrast. Re-evaluate eGFR 48 hours after the imaging procedure; restart metformin if renal function is stable.
eGFR <30 ml/min/ 1.73 m2
Contraindicated
eGFR between 30-45 mL/minute/1.73 m2
Treatment initiation is not recommended
-If eGFR falls below 45 ml/min/1.73 m2 reassess risk and benefit of continuing treatment
 
A clinical trial that influenced the FDA's decision to revise metformin labeling requirements, included 393 patients with T2DM and serum creatinine ranging from 1.47 mg/dL to 2.5 mg/dL.11 Patients were randomized to continue or discontinue metformin over a four-year period. There was no cases of lactic acidosis in either study arm. Patients who discontinued metformin experienced increases in body mass index and hemoglobin A1c.11 A second study, looked at the incidence of lactic acidosis in patients taking metformin. The study design was an observational, longitudinal study of 1,279 patients. This study found a non-significant difference in the incidence of lactic acidosis in the metformin treatment group versus the control group (57/100,000 versus 28/100,000 patient years).12 A third study which included 51,675 participants from 2004 and 2010, found patients with renal impairment on metformin showed no increased risk of CVD, all-cause mortality or acidosis/serious infection.13
The FDA revised guidelines on metformin use in patients with renal impairment to allow greater access to patients who may benefit from its use. Additional studies may be helpful to determine the impact of this change.
 
 
 
References
1. Scheen AJ. Pathophysiology of type 2 diabetes. Acta Clin Belg. 2003;58(6):335-41.
2. American Diabetes Association. Facts about Type 2. Available at: http://www.diabetes.org/diabetes-basics/type-2/facts-about-type-html?loc=db-slabnav. Accessed January 24, 2017.
3. Centers for Disease Control. National Diabetes Statistics Report, 2014. Available at: https://www.cdc.gov/diabetes/pubs/statsreport14/national-diabetes-report-web.pdf
4. Food and Drug Administration. Federal Register, 1979. 44(58). Available at: http://www.fda.gov/ohrms/dockets/ac/98/briefingbook/1998-3454B1_03_WL38.pdf.
5. Umland EM, Klootwyk J. Chapter 37. Acid-Base Disorders. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey L. eds. Pharmacotherapy: A Pathophysiologic Approach, 9e. New York, NY: McGraw-Hill; 2014.
6. Product Information: GLUCOPHAGE(R) XR oral extended-release tablets, metformin HCl oral extended-release tablets. Bristol-Myers Squibb Company (per manufacturer), Princeton, NJ, 2015.
7. Misbin RI 2004. The phantom of lactic acidosis due to metformin in patients with diabetes. Diabetes Care 27 1791-1793.
8. Standards of medical care in diabetes--2014. Diabetes Care. 2014;37 Suppl 1:S14-80.
9. Chan NN, Brain HP, Feher MD. Metformin-associated lactic acidosis: a rare or very rare clinical entity? Diabet Med 1999; 16:273-81.  
10. FDA. Metformin-containing Drugs: Drug Safety Communication - Revised Warnings for Certain Patients With Reduced Kidney Function. Available at: http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm494829.htm. Accessed: 01/24/17
11. Rachmani R, Slavachevski I, Levi Z, Zadok B, Kedar Y, Ravid M. Metformin in patients with type 2 diabetes mellitus: reconsideration of traditional contraindications. Eur J Intern Med. 2002;13(7):428.
12. Kamber N, Davis WA, Bruce DG, Davis TM. Metformin and lactic acidosis in an Australian community setting: the Fremantle Diabetes Study. Med J Aust 2008;188:446-9
13. Ekström N, Schiöler L, Svensson AM, Eeg-Olofsson K, Miao Jonasson J, Zethelius B, et al. Effectiveness and safety of metformin in 51 675 patients with type 2 diabetes and different levels of renal function: a cohort study from the Swedish National Diabetes Register. BMJ Open 2012;2.pii:e001076
 
 

A review of a recently published article: Is initiation of insulin analogs associated with fewer emergency department visits due to hypoglycemia compared to NPH insulin?
 
Authors: Kajal Jain, Pharm.D. Candidate 2019, Allison Kirstie French, Pharm.D.
 
Over 30 million Americans have diabetes, and of those 90-95% have type 2 diabetes. Initial pharmacotherapy consists of metformin followed by other oral agents and basal/bolus insulin. Of these patients, 14-25% will eventually need insulin in order to reach glycemic targets.4 The American Diabetes Association recommends the initiation of insulin therapy in patients with a hemoglobin A1c ≥ 10%, patients with a blood glucose ≥ 300 mg/dL, or markedly symptomatic patients. Basal insulin can be initiated with long-acting insulin analogs consisting of insulin glargine, insulin detemir, and insulin degludec or NPH insulin. Basal insulin analogs are generally administered once daily and NPH insulin is dosed twice daily. Initiation begins with basal insulin at 0.1-0.2 units/kg/day or 10 units/day with adjustments made by 10-15% or 2-4 units once to twice a week.2
 
In clinical studies, basal insulin analogs were shown to have less nocturnal hypoglycemia compared to NPH. While this has been shown, there is no evidence basal insulin analogs reduce the overall risk of severe hypoglycemia or improve glycemic control compared to NPH insulin in type 2 diabetes.3Basal insulin analogs are also more expensive compared to NPH insulin.1 The cost of basal insulin analogs is approximately ten times the cost of NPH insulin. Cost, adverse effects (hypoglycemia), number of injections per day, and goals of therapy (hemoglobin A1c lowering) are all considerations taken into account when initiating a patient on insulin therapy.
 
A recently published retrospective observational study answered the question of w insulin analogs had fewer emergency department and hospital admissions due to hypoglycemia compared to NPH insulin. The study took place at Kaiser Permanente of Northern California and observed 25,489 patients with type 2 diabetes initiated on basal insulin, in the form of insulin glargine/detemir, or NPH insulin, between January 1, 2006 and December 31, 2014. At this institution, physicians had the choice of initiating patients on one of the three options, but were encouraged to initiate patients on NPH insulin due to cost savings.1
 
The primary endpoint was time to hypoglycemia-related emergency department visit or hospital admission after initiation of insulin therapy. The secondary outcome was the change in hemoglobin A1c within one year of insulin initiation.1
 
The 25,489 patients had a mean age of 60.2 years and 46.8% were female. The majority of the patients were white (51.9%) with 9.2% African American, 17.6% Hispanic, and 15.3% Asian. In this patient study group, 23,561 (92%) of patients were initiated on NPH insulin with mean baseline A1c of 9.4%. The remaining 1,928 patients were initiated on basal insulin analogs and had a mean baseline A1c of 9.41%.1
 
The emergency department and hospital admissions events related to hypoglycemia are listed in Table 1. Though not statistically significant, after frequency matching patients with additional adjustment of unbalanced covariates, prior emergency room visits due to hypoglycemia, and time dependent indicators of diabetes medication use, those in the basal insulin analog group were 1.16 times (95% CI, 0.71 to 1.78) more likely to have a hypoglycemia-related emergency room visit or hospital admission compared to NPH insulin. Hemoglobin A1c decreased 0.22% (95% CI, 0.09% to 0.27%) more with NPH insulin compared to insulin analogs, which was found to be statistically significant, but not clinically significant.1
 
 
Table 1: Hospital admission events related to hypoglycemia1
Group
Emergency Department Visits (%)
Hospital Admissions (%)
Mean Follow-up
(mean, 95% CI)
Events/1000 person years
(mean, 95% CI)
Basal Insulin Analogs
(n=1928)
32 (1.66)
7 (0.36)
1.71 (1.62 to 1.79)
11.9 (8.1 to 15.6)
NPH
(n=23,561)
309 (1.3)
45 (0.19)
1.7 (1.68 to 1.72)
8.8 (7.9 to 9.8)
 
 
Limitations of this study include the study was an observational study where care was provided in an integrated healthcare delivery system. The primary outcome also only looked at emergency department or hospital visits related to hypoglycemia, so differences in hypoglycemia otherwise was not accounted for. Regardless of these limitations, the study shows NPH is a viable method of diabetes control for patients requiring insulin therapy that are unable to afford basal insulin analogs. When choosing between basal insulin analogs and NPH for basal insulin, risk of hypoglycemia should not be a determining factor. This plus other factors, such as frequency of injections, nocturnal hypoglycemia, and injection device, should all help determine the best insulin for a patient.1
 
References:
  1. Lipska KJ, Parker MM, Moffet HH, Huang ES, Karter AJ. Association of Initiation of Basal Insulin Analogs vs Neutral Protamine Hagedorn Insulin With Hypoglycemia-Related Emergency Department Visits or Hospital Admissions and With Glycemic Control in Patients With Type 2 Diabetes. JAMA. 2018;320(1):53-62. doi:10.1001/jama.2018.7993
  2. McCulloch DK. General principles of insulin therapy in diabetes mellitus. UpToDate.
  3. McCulloch DK. Patient education: Hypoglycemia (low blood sugar) in diabetes mellitus (Beyond the Basics). UpToDate.
  4. Type 2 Diabetes. Centers for Disease Control and Prevention.


 
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