Reece's Piece's In a Diabetes World

Contributors: Shatiya Grant and Pegah Tavana, PharmD Candidates Class of 2022, PCOM Georgia School of Pharmacy

VG, a 62-year-old female, has lived with type 2 diabetes for the past fifteen years.  She has tried numerous medications for treatment of her diabetes. VG has been frustrated that many of the medications will lower her glucose; however, they also increase her risk of having low glucose and leaves her feeling hungry.  She has struggled with achieving and maintaining a healthy weight for years, and just simply wants to find a medication that will lower her glucose and help her lose weight.  Today, she has a six month visit with her primary care provider (PCP) to check her hemoglobin A1c (A1c).  Her A1c is 9%.  Her PCP mentions a medication, semaglutide, as a possible treatment option for her diabetes, and VG is excited it comes in either a pill or injection formulations.  VG’s PCP encourages her to research this medication before committing to taking it for her diabetes.

Rybelsus® and Ozempic® are both brand names for a drug called semaglutide, both are FDA approved to control blood sugar levels in persons with type 2 diabetes; however they each have a unique form of delivery. Semaglutide is a glucagon-like peptide-1 (GLP-1) analogue which acts by activating a GLP-1 receptor that is found in the pancreas and this leads to improved insulin release. It also works on the liver by blocking release of excessive amounts of glucose and delays gastric emptying so one feels full longer, and lastly works in the hunger center in the brain to suppresses appetite. This leads to weight loss and can be seen as a favorable side effect from the drug. Additionally, semaglutide provides cardiovascular risk reduction benefits, which decreases risk of having a heart attack, stroke, and death.

Rybelsus® is a once daily pill, whereas Ozempic® is a once weekly injection, which is a longer-acting dosage form. Rybelsus® is available in 3mg, 7mg and 14mg. It is recommended to start Rybelsus® with a 3mg tablet taken once daily in the morning on an empty stomach with 4oz of water for the first 30 days and then the dose may be increased to 7mg and then again to 14mg.  Ozempic® is a prefilled single injection pen, which is administered subcutaneously into the abdomen, upper arm, or thigh. The usual starting dose is a 0.25 mg injection once a week (on the same day each week) and may need to be increased to 0.5mg after 30 days then 1mg after another 30 days depending on shared decision making of the person with diabetes and their healthcare provider. It is strongly recommended that you rotate the injection site each time and to not inject in the same spot due to fatty deposits which may not allow the drug to be absorbed as well and cause it to be less effective. If a dose is missed within 5 days, take it as soon as possible. However, if it has been longer than 5 days, skip the dose and continue the next dose as scheduled. Unused Ozempic® pens are stored in the refrigerator, but once used it can be stored at room temperature or refrigerated.

Both Rybelsus® and Ozempic® have similar side effects. Gastrointestinal symptoms such as nausea, vomiting, diarrhea, and abdominal pain are the most common side effects. These adverse effects appear to be dose-related which is why it is advisable to start at a lower dose so that your body can get accustomed to the drug before increasing the dose. Ozempic® is an injection so it is important to note that some people may also experience injection site reactions that include redness, swelling, itching, and stinging. This is generally no cause for concern and goes away in a few days. It is also important to be aware that these medications have been associated with acute pancreatitis and may also mask the initial signs of pancreatitis including nausea, vomiting, and abdominal pain. People who have been diagnosed with or have had a family member diagnosed with medullary thyroid carcinoma or multiple endocrine neoplasia type 2 should not use any form of semaglutide. This medication has not been studied in persons with gastroparesis. Since semaglutide delays gastric emptying, it is not recommended for persons with gastroparesis.

Semaglutide is a wonderful drug in the world of diabetes and offers many benefits to people including cardiovascular benefits, weight loss, and of course reducing blood sugar levels. Ozempic® offers the benefit of once-weekly dosing which may be a benefit for some patients. While others may lean towards Rybelsus® since they can get the same great health benefits without the need for an injection. To conclude, selection of the most appropriate formulation can be made on an individual basis to best suit their preferences and needs.

Back to VG, after she completes her thorough research, she agrees with her PCP that semaglutide would be a good option.  While talking with her PCP a couple of weeks after her office visit, VG and her PCP choose the once daily, Rybelsus®. They both feel this treatment is most ideal since VG has a needle phobia and prefers oral over injectable formulation.  VG shares her excitement with her best friend, who also has type 2 diabetes, about the oral semaglutide she is now taking  and how it has improved both her glucose values and her weight loss.  VG’s best friend decides to talk with her PCP about the possibility of semaglutide for treatment of her diabetes because she really likes the idea of a once weekly injectable formulation.

References:

Meier JJ. GLP-1 receptor agonists for individualized treatment of type 2 diabetes mellitus. Nat Rev Endocrinol (2012) 8:728–42.  10.1038/nrendo.2012.140

European Medicines Agency. Ozempic® Summary of Product Characteristics. Available at: https://www.ema.europa.eu/en/documents/product-information/ozempic-epar-product-information_en.pdf (Accessed February 2, 2022)

Food and Drug Administration . Rybelsus® Prescribing Information. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/213051s000lbl.pdf (Accessed February 3, 2022).

Contributor: Ahmed Mawri, PharmD Candidate Class of 2022, PCOM Georgia School of Pharmacy

Biologic medications are commonly used to treat conditions such as Crohn’s disease, ulcerative colitis, rheumatoid arthritis, and many others. Biologic insulins, such as Basaglar®, are becoming more popular today and will become even more prevalent in the future for the treatment of diabetes. Previously, there were concerns with potential differences in the efficacy and safety between the biosimilar product and its reference insulin. However, after the recent FDA approval of Semglee®, a true biosimilar biologic, those concerns can be put to rest as it has been proven to be noninferior in efficacy while maintaining similar safety profiles to its reference insulin. What is even more special about Semglee®, is that it became the first interchangeable biosimilar product in the U.S. to receive FDA approval on July 28^th, 2021. 

 It is important we define the terms interchangeable and biosimilar.  

 -Biosimilar: A biosimilar is a biological product that is highly similar to and has no clinically meaningful differences from a biological product already approved by the FDA (also called the reference product). In simpler terms, you can expect the same safety and effectiveness from the biosimilar as you would the reference product  

-Interchangeable: An interchangeable biosimilar product may be substituted for the reference product without the intervention of the prescriber. The  substitution may occur at the pharmacy similar to how generic medications are substituted for brand name drugs.  

 Approval of these insulin products can provide patients with additional safe, high quality, and potentially cost-effective options for diabetes therapy. It may be difficult to differentiate a biosimilar insulin to a generic drug. Conceptually, they are very similar, but the term “generic” is used only when referring to nonbiologic/small molecule medications because they contain the exact same active ingredient as their reference drug (brand name). Whereas insulin is a large protein which cannot be precisely replicated so they do not contain the same exact active ingredient. There are even differences between the very same biosimilar medications with different lot numbers.  

How are biosimilars approved?  

FDA approval of all biologics requires thorough and exhaustive investigation to ensure safety and efficacy. The reference drug is the single biologic which is already approved by FDA.  The reference drug is what the proposed biosimilar product is compared to. The goal of developing a biosimilar product is to provide data comparing the proposed biosimilar to its FDA approved reference product to demonstrate biosimilarity. Instead of generating the same full profile of nonclinical and clinical data as the reference drug, the manufacturer must only show that the proposed biosimilar product is highly similar to, and has no clinically meaningful differences from the FDA approved reference product.  

 This is done by including data from analytical studies, animal studies, and clinical studies.

 -Analytical studies demonstrate that the biological product is highly similar to

the reference product by providing chemical information about the biologic’s

purities, contaminants, and quality.

 -Animal studies help assess toxicity of the proposed biosimilar product 

- A clinical study or studies sufficient to demonstrate safety, purity, and potency of the proposed biosimilar product in one or more of the indications for which the reference product is licensed. This typically includes assessing immunogenicity, pharmacokinetics, and, in some cases, pharmacodynamics and may also include a comparative clinical study. 

In March 2010, Congress passed the Biologics Price Competition and Innovation Act of 2009 (BPCIA), which created an expedited route for approval of biosimilars to provide the public with more access to safe and effective biologic products. The expedited pathway provides more treatment options potentially reducing drug costs through competition. The abbreviated licensure pathway does not mean that the biosimilar product is held to a lower standard. The data required for approval of a biosimilar or interchangeable product is extensive.  If a biosimilar manufacturer can demonstrate that its product is biosimilar to the reference product, then it is scientifically justified to rely on existing scientific knowledge about the safety and effectiveness of the reference product to support approval. This allows for a potentially shorter and less costly drug development program for a biosimilar.  

 Biosimilar insulins provide us with additional safe, high-quality options for treatment of diabetes. The abbreviated licensure pathway allows for faster access to these medications and allows for competition among the manufacturing of these drugs which could lead to more cost-effective options.  

References

Blevins, TC, Barve, A, Sun, B, et al. Efficacy and safety of MYL-1501D versus insulin glargine in patients with type 2 diabetes after 24 weeks: Results of the phase III INSTRIDE 2 study. Diabetes Obes Metab. 2019; 21: 129– 135.  https://doi.org/10.1111/dom.13495  

Kim AP, Bindler RJ. The Future of Biosimilar Insulins. Diabetes Spectr. 2016;29(3):161-166.  doi:10.2337/diaspect.29.3.161  

Center for Drug Evaluation and Research. Biosimilar development, review, and approval.U.S. Food and Drug Administration, https://www.fda.gov/drugs/biosimilars/biosimilar-development-review-and-approval.  Published October 20, 2017. Accessed October 28, 2021.

Special thanks to Joanna Ho, PharmD Candidate Class of 2022 PCOM Georgia SOP, for reviewing blog

To learn some create tips on how to pay for and manage diabetes treatment, please click on the link below for an article in Money Greek.

https://www.moneygeek.com/insurance/health/paying-for-and-managing-diabetes-treatment/#expert=sara-mandy-reece

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#money #saving #diabetes

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The annual time for selecting a Medicare Part D plan for 2022 has arrived. If you or a family member are Medicare eligible and on insulin therapy, please make sure to select a Part D program that has Senior Savings Model for insulin (or has a insulin savings model). Also, make sure to select enrollment in the Senior Savings Model once you enroll in the Medicare Part D plan with Senior Savings Model. This model will provide for reduced monthly costs for insulin. Please click on the link below to learn more.

https://www.medicare.gov/drug-coverage-part-d/what-medicare-part-d-drug-plans-cover

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Tirzepatide, a novel drug that activates both GLP – 1 and GIP receptors in the body, has additional promising results from SURPASS trials. Below is a brief summary of the findings for tirzepatide in these trials.

SURPASS-3 CGM Sub-Study: More time in tight target range, improved glycemic variability and numerically less time in hypoglycemia compared to titrated insulin degludec in adults with type 2 diabetes. Also, in one exploratory endpoint, those taking the highest dose of tirzepatide (15 mg) spent up to 91.2% of the day in the target time in range (71-180 mg/dL), compared to 75% for those taking insulin degludec.

SURPASS-3 MRI Sub-Study: Greater reductions in liver fat content compared to titrated insulin degludec in adults with type 2 diabetes. Additionally, the volume of abdominal adipose tissue decreased with tirzepatide, compared to an increase with insulin degludec. These results of this study are important because increased ectopic fat (i.e. liver fat or visceral adipose tissue) is commonly seen in adults with type 2 diabetes and is associated with an inflammatory response and increased cardiometabolic risk.

SURPASS-4 Detailed Results: Superior A1C and body weight reductions compared to insulin glargine and continued to demonstrate consistent A1C and weight control for up to two years in newly released data from this study.

To learn more, please click on links below.

https://investor.lilly.com/news-releases/news-release-details/lillys-tirzepatide-led-greater-time-range-compared-insulin

https://investor.lilly.com/news-releases/news-release-details/lillys-tirzepatide-led-greater-improvements-liver-fat-content

https://investor.lilly.com/news-releases/news-release-details/lillys-tirzepatide-achieves-all-primary-and-key-secondary-study

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Contributor: Zachary Powell, PharmD Candidate Class of 2023, PCOM Georgia School of Pharmacy

Sticker shock! LW was slammed when he  went  to pick up his insulin prescription.  What?? More than $200 for a pack of insulin pens. How is  this  possible? He thought, “I  will need to take out a loan  to afford this medication.” LW had just been discharged from the hospital after an emergency high blood sugar level occurrence and learned that he has diabetes. He was told “…you are  fortunate you will only need one insulin injection per  day…”  Really?? He was scared to stick himself and horrified at the cost of this medicine.  

Insulin affordability is at the forefront of persons with diabetes, their loved ones, and their healthcare professionals.  Interestingly, Walmart recently announced a partnership with Novo Nordisk to begin selling the rapid-acting insulin analog, Novolog (insulin aspart), under the Walmart branding ReliOn.  For several years, the partnership between Walmart and Novo Nordisk has included affordable, over-the-counter (OTC) human insulins including regular insulin (short-acting), NPH (intermediate-acting), and 70/30 combination, starting at $25 per vial.  The ReliOn human insulin provided another option for persons with diabetes struggling to afford the insulin price hikes within the last two decades leaving many people to ration their insulin and, in some instances, die.  Simply that.  Using human insulin, however, raises its own safety and efficacy concerns in managing glycemic variability for persons on insulin therapy. 

“But the word ‘human’ in this insulin means it’s natural and safer, right?”  Not quite.  Diabetes is a complex disease which may impact one individual much differently than another.  According to the CDC, as of June 2020 more than 34 million people in the US have diabetes, each requiring an individualized plan; not only focused on their medication therapy but also an individualized diet and exercise plan.  Human insulins, though potentially helpful in a pinch, aren’t as versatile for managing diabetes when compared to insulin analogs..  There are three important characteristics to keep in mind when discussing the different types of insulins: onset of action – how quickly the insulin works; peak – how long it takes for the insulin to reach the maximum therapeutic benefit; and duration – how long the action of the insulin lasts.  Newer, more expensive insulin analogs differ in their molecular structure when compared to human insulin and allows healthcare providers to fine tune insulin requirements for each individual because these molecular modifications change our 3 important characteristics: onset of action, peak, and duration.  On the other hand, human insulin is cheaper but puts the person with diabetes at risk of experiencing wide fluctuations in their blood glucose and could ultimately be life-threatening without proper supervision from a healthcare provider.

With the announcement of Walmart’s new insulin analog, it may begin a much needed trend towards affordable insulin for diabetics.  The insulin analog, ReliOn Novolog, is now available with a prescription as 10 mL vials priced at $72.88 as well as 3 mL single-patient pens and 3 mL single-patient PenFill cartridges starting at $85.88.  Though the prices are still substantial, especially for individuals who require multiple vials and pens each month, the $73 vial and $86 pens provide individuals with a 58% and 75% discount off branded insulin analogs, respectively.  This correlates to a savings of $100 per vial and $250 per package of pens.  

Available reduced cost insulin at Walmart

• Insulin aspart (100 units/mL; U-100) — analog 
  • 10 mL multiple-dose vial 
    • $73
  • 3 mL single-pt use PenFill cartridges for the 3 mL PenFill cartridge device 
  • 3 mL single-pt use NOVOLOG FlexPen 
  • 3 mL single-pt use NOVOLOG FlexTouch 
    • $86/box (5 pens/box)
• Human insulin 10 mL vials 
  • $25/vial
  • ReliOn Novolin R U-100 (short acting) 
  • ReliOn Novolin N (intermediate acting) 
  • ReliOn Novolin 70/30 (combination of intermediate-acting and short-acting) 

There is still work to be done to make insulin more affordable for diabetic patients but Walmart is fulfilling their slogan “Save money. Live better.”  Another area to improve would be the reduction in cost of long-acting (basal) insulin analogs.  The longer acting insulins are the go-to for healthcare providers as they allow for better control of glucose levels but also carry a larger cost to patients.  

Back to LW, he shared with the pharmacist that he had not seen a primary care provider in years since he went a few years without health insurance and recently began a new job and health insurance. The pharmacist provided guidance for LW in finding a primary care provider for ongoing care for his diabetes and walked LW through the website, getinsulin.org, to explore available financial resources. 

References

1. https://www.cdc.gov/diabetes/basics/quick-facts.html 

2. https://www.healio.com/news/endocrinology/20210701/walmart-launches-first-and-only-private-brand-analog-insulin?utm_source=selligent&utm_medium=email&utm_campaign=topicalert&M_BT=4557970002905 

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Currently, dapagliflozin (Farxiga) is best known for its indication for treating type 2 diabetes, reducing hospitalization for heart failure (even in persons without diabetes) and delaying progression of chronic kidney disease in type 2 diabetes. Well, it is not alone. FDA recently approved finerenone (Kerendia) for delaying progression of diabetes related chronic kidney disease in persons with type 2 diabetes. Additionally, it has been approved for reducing cardiovascular (heart) death, non-fatal heart attacks and hospitalization for heart failure so bottom line it helps with protecting heart and kidneys. This medication works by blocking mineralocorticoid receptor activation in kidney which decreases fibrosis and inflammation. It is a once daily medication available in 10 mg and 20 mg. Please keep in mind that it will take time for insurance plans to add this new medication to their drug formulary (list of preferred medications that they cover under their health plan). To learn more, please click on link below.

https://www.medpagetoday.com/nephrology/diabetes/93515

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I am beyond thrilled that Medicare has removed the requirement of testing glucose four times daily for Medicare beneficiaries to qualify for CGM. This requirement has been a burden for many and created a barrier for access to CGM. Medicare will continue at this time to require Medicare beneficiaries to be on a basal bolus insulin regimen to qualify for CGM. Additionally, a c-peptide and fasting glucose level is often required prior to approval of CGM. Please click on link below to learn more from my dear colleague, Kate Thomas with ADCES, regarding this important update in Medicare requirements for CGM.

https://www.diabeteseducator.org/news/perspectives/aade-blog-details/adces-perspectives-on-diabetes-care/2021/06/14/medicare-updates-cgm-benefit

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#Medicare #CGM

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I am beyond excited about the FDA approval of semaglutide 2.4 mg for weight loss. This medication has been absolutely amazing in reducing glucose and cardiovascular (heart related) risk (for stroke and heart attack) in persons with diabetes in many persons with diabetes that I know personally. In my experience, I have seen first hand off label use for weight loss in persons without diabetes. Four trials, Semaglutide in Treatment Effect in People with Obesity (STEP), (STEP 1 – 4) compared semaglutide 2.4 mg versus placebo (no drug), and the results proved the effectiveness of semaglutide 2.4 mg in reducing weight in persons without diabetes. Please click below for additional information.

https://www.medscape.com/viewarticle/952441?src=wnl_newsalrt_210604_MSCPEDIT&uac=293412PG&impID=3421015&faf=1

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Dapagliflozin is a game changer as this medication addresses renal and cardiovascular protection even in folks without diabetes. In this most recent study (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure [DAPA-HF], the safety and efficacy of dapagliflozin 10 mg vs placebo in a randomized, double-blind, placebo-controlled trial of patients heart failure (HFrEF) was evaluated with primary outcome of the composite of an episode of worsening HR or cardiovascular death. The association found in this study is promising. To learn more, please click below.

Butt JH, Docherty KF, Petrie MC, et al. Efficacy and safety of dapagliflozin in men and women with heart failure with reduced ejection fraction: a prespecified analysis of the Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure trial. JAMA Cardiol. Published online March 31, 2021. doi:10.1001/jamacardio.2021.0379

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#dapagliflozin #heartfailure #benefits

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