Reece's Piece's In a Diabetes World

Marge, 68-year-old female with type 2 diabetes, presents for her 3 month follow up visit with her primary care provider (PCP).  She suspects that her hemoglobin A1c (A1c) is going to be up and is unsure of what exactly her goal A1c is after some particularly tough months emotionally and physically.   She is nervous that her provider may recommend insulin, and her sister said that insulin is not safe.  Marge is also curious whether one of these “GLP-1 agonists” might be good for her since her best friend (who also has type 2 diabetes) raves about her experience taking a GLP-1 agonist.  She bravely enters her PCP’s office determined to face her A1c regardless of what her number is, and advocates for herself in the treatment decision making process. The office visit begins well, then her provider enters the room and shares Marge has an A1c of 10%. 

Marge is not alone in her hesitation about insulin. Well-meaning friends and family weighing in on their opinion regarding the use of insulin can be a roadblock for providers.  The goal is for any treatment decision to incorporate shared decision making where both the person with diabetes and their provider have a voice in the final treatment selection.  The 2025 American Diabetes Association (ADA) Standards of Care in Standard 9 recommends GLP-1 agonist or dual GIP and GLP-1 agonist be considered in most individuals with type 2 diabetes prior to insulin.  These standards also recommend insulin use in type 2 diabetes when A1c is at or above 10% of glucose is at or above 300 mg/dL. Marge has A1c of 10%. So for Marge and her provider what are considerations beyond A1c that can help guide the selection of GLP-1 agonist or insulin?  What are the pros and cons of GLP-1 agonist versus?

Per the 2025 ADA Standards of Care, below are considerations when selecting therapy in type 2 diabetes.  Historically, the focus for treatment of type 2 diabetes was primarily glucose goal achievement and maintenance however those days are long gone.  The reduction of cardiovascular and kidney risk is now center stage as type 2 diabetes occurs on a cardiometabolic renal spectrum.

-Presence of or high risk for ASCVD

-Heart failure

-Chronic kidney disease

-Weight management

	Pros (Benefits)	Cons (Side Effects)
GLP-1 agonists	-Effectively lowers glucose and hemoglobin A1c-Cardiovascular (reduction in major adverse cardiovascular events (MACE) in those with or high risk of cardiovascular disease) ** -Renal (reduce persistent eGFR reduction and cardiovascular death in those with T2DM and chronic kidney disease) ** – Liver (potential benefit in MASLD or MASH) ** – Weight loss	-Constipation or diarrhea -Nausea -Risk of pancreatitis -Risk of gallbladder disease -Risk of thyroid C-cell disease
Insulin	-Effectively lowers glucose and hemoglobin A1c	-Weight gain -Hypoglycemia

**Benefit varies based on individual GLP-1 agonists

Back to Marge, a bit more about her clinical history as she has had NSTEMI (myocardial infarction in 2020), stage 3a chronic kidney disease and BMI of 28. She is also interested in trying out a continuous glucose monitor as she is tired of pricking her finger.  She is okay with injections but not any weight gain or low glucose values (as she lives alone).  She and her PCP spend about 10 minutes going through pros and cons of insulin versus non-insulin injectable.   They decide on a GLP-1 agonist in particular injectable semaglutide (Ozempic) due to the additional benefit considering her having CKD, established ASCVD and having elevated A1c. Oral semaglutide does not currently have the additional cardiometabolic renal indications.  Per the 2025 ADA Standards of Care Standard 6, an appropriate goal A1c for Marge considering her multiple co-morbidities would be < 8%.

References:

Pharmacologic Approaches to Glycemic Treatment: Standards of Care in Diabetes – 2025. American Diabetes Association Professional Practice Committee. Diabetes Care. 2025; 48 (supplement 1):S181-S206.

Glycemic Goals and Hypoglycemia: Standards of Care in Diabetes – 2025. American Diabetes Association Professional Practice Committee. Diabetes Care. 2025; 48 (supplement 1):S128-S145.

Contributor: Seana-Pierre Williams, PharmD Candidate 2025, PCOM Georgia School of Pharmacy

The use of insulin therapy to control elevated glucose levels in patients with diabetes adds a layer of complication in diabetes management due to the potential risk of over-treatment resulting in hypoglycemia. Hypoglycemia, in patients with diabetes, is typically characterized as having a blood glucose level below 70 mg/dL. This subsequent hypoglycemia can have a greater effect on morbidity and mortality for patients with type 1 diabetes, who are reliant on exogenous insulin, and extreme hypoglycemic events are directly associated with substantial overall health care costs.¹

Glucagon is a hormone produced by the pancreas that stimulates the liver to release glucose to replenish blood glucose therefore maintaining glucose homeostasis. Historically, exogenous glucagon was supplied as a powder that must be reconstituted into a solution before delivery due to glucagon’s instability in solution. One of the primary challenges in formulating exogenous glucagon is maintaining its stability over time. Glucagon is inherently unstable and can degrade when exposed to various conditions, such as temperature changes, pH fluctuations, and agitation.² The traditional reconstitution process of glucagon from powder to liquid has been a barrier to swift and efficient administration during emergencies.² Gvoke HypoPen is an autoinjector device developed by Xeris Pharmaceuticals that provides a convenient and user-friendly way to administer glucagon in cases of severe hypoglycemia and was approved by the FDA in 2019. The medication device is supplied as an auto-injector and prefilled syringe for subcutaneous injection only containing a freeze-dried powder glucagon, a surfactant, an antioxidant and chelating agent combined with a polar liquid to prevent instability. The formulations are available in two premeasured doses: a 0.5 mg/0.1 mL dose for pediatric administration and a 1 mg/0.2 mL dose for adolescent and adult administration. Gvoke (Glucagon) injection is an antihypoglycemic agent indicated for the treatment of severe hypoglycemia in pediatric and adult patients with diabetes ages 2 years and above. Severe hypoglycemia is classified as a blood glucose level below 54 mg/dL and requires immediate treatment.

Potential advantages of Gvoke include the ease of use due to its auto-injection formulation, the absence of need for reconstitution and potentially the time to resolution of hypoglycemia in comparison to other delivery systems such as the Glucagon Emergency Kit (GEK). According to Cummins et al in a phase three comparison of a ready-to-use liquid glucagon rescue pen to glucagon emergency kit for the symptomatic relief of severe hypoglycemia, the auto-injector was shown to have a significantly higher success rate in delivering a full glucagon dose during simulated emergencies with both trained and untrained users. Additional advantages include the presence of a sheath protected needle that retracts into the auto-injector which reduces the incidence of needle sticks, the device can be stored for two years at room temperature and a reduction in injection site pain due to a smaller injected volume. A potential disadvantage of Gvoke is the potential for nausea and vomiting as the nonaqueous solution is delivered subcutaneously.¹ Drug interaction considerations include patients who are currently prescribed beta blockers, indomethacin and warfarin. Patients prescribed beta blockers may have a transient increase in pulse and blood pressure, Gvoke may may lose its ability to raise glucose or may produce hypoglycemia with use of indomethacin and risk of increased anticoagulant effects with warfarin.  

Key Counseling Points for Patients and Their Caregivers⁴:

• Be aware of signs and symptoms of hypoglycemia as severe hypoglycemia requires immediate treatment. Administer Gvoke as soon as severe hypoglycemia is recognized
• Signs and symptoms of hypoglycemia include but is not limited to shaking, sweating, fast heartbeat, extreme hunger, confusion, irritability, dizziness and blurred vision.
• Visually inspect the Gvoke product prior to administration. The solution should appear clear and colorless to pale yellow and be free of particles. If the solution is discolored or contains particulate matter, do not use.
• Store medication in its original sealed foil pouch until time of use
• Administer the injection in the lower abdomen, outer thigh, or outer upper arm according to printed instructions for use on packaging. Call for emergency assistance immediately after administering the dose.
• When the patient has responded to treatment, give oral carbohydrates to prevent recurrence of hypoglycemia.
•  Do not attempt to reuse Gvoke as each device contains a single dose of glucagon and cannot be reused.
• Allergic reactions can occur with Gvoke therefore seek immediate medical attention if they experience any symptoms of serious hypersensitivity reactions

Accessibility of Gvoke can be influenced by various factors including cost, insurance coverage and patient education. The future of glucagon delivery holds the promise of transforming hypoglycemia management, revolutionizing the way individuals with diabetes respond to low blood sugar episodes. Several avenues of innovation are shaping the future of glucagon administration, aiming to enhance its efficacy, ease of use, and overall patient experience.³

References:

1. Damianne Brand-Eubanks; Gvoke HypoPen: An Auto-Injector Containing an Innovative, Liquid-Stable Glucagon Formulation for Use in Severe Acute Hypoglycemia. Clin Diabetes 1 October 2019; 37 (4): 393–394.
2. Kumar, Samarth et al. “Glucagon: Delivery advancements for hypoglycemia management.” International journal of pharmaceutics vol. 652 (2024): 123785. doi: 10.1016/j.ijpharm.2024.123785
3. Christiansen M, Cummins M, Prestrelski S, Junaidi K. A phase 3 comparison of a ready-to-use liquid glucagon rescue pen to glucagon emergency kit for the symptomatic relief of severe hypoglycemia. Poster presented at the Diabetes Technology Society’s Diabetes Technology Meeting, 8–10 November 2018, Bethesda, Md
4. Gvoke-Accessdata.Fda.Gov, www.accessdata.fda.gov/drugsatfda_docs/label/2021/212097Orig1s007lbl.pdf. Accessed 12 Dec. 2024.

Contributor: Zuhal Saadut, PharmD Candidate 2025, PCOM Georgia School of Pharmacy

Meet Jana, a 48-year-old female that was recently diagnosed with prediabetes at her most recent primary care visit, with an A1c of 6.3%. She was upset when she found out about her diagnosis as her father had type 2 Diabetes. He had several incidences of extreme hyperglycemia, or high blood sugar, that required hospitalization. Her father also experienced vision loss due to many years of poor blood sugar control. Jana is afraid of these things potentially happening to her and wants to keep a close eye on her blood sugar levels without having to prick her finger every day and carry a blood glucose meter kit everywhere she goes. She is determined to gain control of her health again and signed up for nutrition classes and a gym membership to improve her dietary intake and physical activity. With these lifestyle changes, she wants to see how fast it will work. Jana is curious about the use of continuous glucose monitoring but does not want to go through the prescription process because her “insurance sucks anyways”.

As of March 5th, 2024, the U.S. Food and Drug Administration (FDA) has approved its first over the counter (OTC) continuous glucose monitoring (CGM), the Dexcom Stelo Glucose Biosensor. This product is intended for individuals ages 18 and older that either do not use insulin to treat their diabetes or want to check their blood glucose trends as they eat or exercise. This system does not have the ability to warn patients if they are experiencing hypoglycemia, or low blood sugar (<70 mg/dL), therefore is not meant for individuals with problematic hypoglycemia.

Dexcom Stelo is a sensor that is applied in a similar fashion as other CGM sensors, with wear time that can last up to 15 days. A study was conducted on the sensor wear time and showed that 77.9% of sensors last the full 15 days. The remaining sensors did not last for 15 days, with 10% of them lasting less than 12 days. The sensor must be paired with a smartphone device that is compatible with the Dexcom application to be downloaded. A Dexcom account must also be created before the sensor can be used. The readings of your blood sugar will appear on the app and updates every 15 minutes. Dexcom Stelo is currently not available in the market, but according to their manufacturers, it should be available Summer 2024 for online purchase.

Abbott has also obtained FDA approval for OTC CGMs (Lingo and Libre Rio) as of June 10th, 2024. Lingo is intended for individuals ages 18 and older that are looking to improve their overall health and wellness, with a sensor wear time of 14 days. Libre Rio is intended for individuals ages 18 and older with Type 2 Diabetes that do not use insulin therapy, with sensor wear time of up to 15 days, measuring blood sugars ranging from 40 to 400 mg/dL. Both of these sensors require smartphone devices compatible with their respective applications and an account must be created before use of the sensor. Neither product from Abbott is available on the market yet, however, Lingo is estimated to be available for purchase Summer 2024. As of right now, there is no estimated time of when Libre Rio will be available for purchase.

The OTC CGMs differ from the prescription CGM as they have an age restriction and are recommended to not be used in individuals with type 1 diabetes or those with type 2 Diabetes on insulin therapy or incidences of hypoglycemia. If you notice constant high or low readings of your blood sugar, be sure to consult your healthcare provider before taking any action of adjusting your medication doses. Adverse effects of sensor use include local infection, skin irritation and pain or discomfort.

Fast forward to 6 months later, she was looking forward to her follow up appointment with her doctor to find out what her new A1c would be after these lifestyle modifications. Results came back with an A1c of 5.3%! Her doctor applauded her for taking the initiative for her health. Jana is relieved that she was able to prevent herself from getting Diabetes before it was too late and will continue to do her best to stay healthy.  Jana is happy that she has the option to monitor her blood sugar levels without having to prick her finger daily and loves that the results are digital on her phone.

References:

• https://www.fda.gov/news-events/press-announcements/fda-clears-first-over-counter-continuous-glucose-monitor
• https://www.dexcom.com/stelo?sfc=7014y000000zbBPAAY&gad_source=1&gclid=CjwKCAjwm_SzBhAsEiwAXE2Cv2_hWxtpvxHKBeCsnM7QgiPMyrEyYy6GPT3gTJun9hBN2PF96-UH7RoCBmAQAvD_BwE

https://abbott.mediaroom.com/2024-06-10-Abbott-Receives-U-S-FDA-Clearance-for-Two-New-Over-the-Counter-Continuous-Glucose-Monitoring-Systems

Contributor: Seana-Pierre Williams, PharmD Candidate 2025, PCOM Georgia Campus School of Pharmacy

Earlier this year both Dexcom and Freestyle Libre stormed the Diabetes Technology market with an upgraded continuous glucose monitor (CGM). The new Freestyle Libre 3 and Dexcom G7 continuous glucose monitors will provide a significantly smaller device size and a highly anticipated enhancement in the devices’ features to improve the patient’s overall experience. Here’s what you should know about these new and improved versions of the CGM systems. 

Dexcom G7

The G7 is approximately 60% smaller than the previous G6 model and boasts a more circular shape. The sensor and transmitter have now been combined into one disposable device. The G7 now has a reduced warm up time from two hours with the G6 to now 30 minutes with the G7. Upon completion of the warmup period, the sensor will begin automatically. The wear time of the G7 remains the same as the previous G6 model, 10 days, with one major upgrade. The G7 sensors now carry a 12- hour grace period to replace an expiring sensor and new customizable alerts along with the ability to temporarily silence alarms. The mobile app for iOS and Android users- the Dexcom CGM app for the G7 is also redesigned to provide a “Clarity Card” which is a data summary of average glucose, Glycemic Management Indicator (GMI) and Time in Range (TIR) for the past 3, 7, 14, 30, or 90 days. The Dexcom G7 sends the glucose readings approximately every five minutes to the smartphone app or a receiver. The G7 reader or the smart phone being used can receive information from 20 feet away and stores up to 24 hours of data in case the phone or receiver is out of range. Once the receiving device is back in range, the data will be transmitted. The application of the G7 remains user friendly with the presence of a button on the applicator to press down to release the sensor.

Freestyle Libre 3

The Freestyle Libre 3 now provides real-time glucose readings sent to a compatible smartphone and can now be viewed with a quick glance without the need to scan. The sensor is now comparably smaller than the Libre 2 system, measuring at approximately 21mm in diameter with a new simple one piece applicator and optional real-time glucose alarms. The Libre 3 retains the 60-minute warmup period and the sensor starts upon first scan as with the Libre 2. The wear time for the Libre 3 remains the same as the previous Libre 2 model, 14 days. The Freestyle Libre 3 now sends the glucose readings automatically to the user’s smartphone every minute and can receive information from up to 33 feet away. The sensor stores 14 days of data in case the smartphone is out of range of the sensor. The Libre 3 now carries a new, simple one-piece applicator which requires a slight push down on the applicator to insert the sensor.

Affordability and Insurance

From an affordability and insurance standpoint, both the Dexcom and Libre 3 manufacturers offer programs to allow access to their respective CGM systems. Dexcom offers the “Dexcom G7 Simple Start” program for those with commercial insurance whose insurance plans have not yet added the G7 to their coverage. Under this program, the G7 sensors can be purchased for $89 a month at local pharmacies until coverage is added. Freestyle Libre offers a “Free Trial” program for eligible individuals to receive a free voucher for a trial of the system. This free trial comes with additional resources to help the new user get off to a good start. Commercially insured patients may pay up to $75 per month (depending on an individual’a coverage plan) for the sensors and is said to be more affordable than other CGM systems. Those who have questions regarding the Libre 3 sensors or are asked to pay over $75 can contact Freestyle Libre.  For those with Medicare coverage, both Dexcom G7 and the Freestyle Libre 3 are covered for eligible persons with diabetes.

What do these updates in both CGM systems mean for the person with diabetes?

Seana-Pierre Williams offered to give an insight on how the cutting edge CGM technology has impacted her overall management of diabetes. As a person with diabetes who has struggled with type 1 Diabetes for 15 years, continuous glucose monitoring has been pivotal in managing this chronic illness. Seeing my blood glucose in real time allows for more accurate treatment decisions which I have used to improve the overall control of my diabetes. Having alerts to keep me on track offers me peace of mind especially since I live a very active lifestyle.  I can feel confident and safe that my CGM will alert me in times when I am outside of my blood glucose target ranges. Hypoglycemia is a life-threatening risk when using blood glucose lowering treatments, especially insulin since I am insulin dependent. Smaller size sensors offer me more discretion and comfort since I am constantly wearing a sensor. There is also the additional benefit of not having to finger stick unless my symptoms do not match what my CGM is displaying. Having used multiple CGM systems over the years, there are pros and cons with both Dexcom and Freestyle Libre. With the upgrades in Freestyle Libre 3 and Dexcom G7, more patients, like me, are able to manage our Diabetes with more comfort and confidence and can focus on living a normal day to day life. Once Diabetes has entered the discussion, your world is turned upside down. From lifestyle modifications to pharmacological intervention, continuous glucose monitoring is a powerful tool helping me to stay on top of things! When choosing a continuous monitor, just remember that each patient’s experience is unique. There are several patient factors that should be considered when deciding what CGM is best for you.

https://www.diabeteseducator.org/danatech/glucose-monitoring/continuous-glucose-monitors-(cgm)/cgm-selection-training/dexcom-g7-libre-3-comparison

Contributor: Krishna Chavada, PharmD Candidate 2024, PCOM Georgia School of Pharmacy

Based on self-reported data, 1.3 million American adults have been diagnosed with Type 1 diabetes and use insulin. Maintaining blood glucose levels can become very difficult and it can become a burden to such patients’ lifestyle. To better manage such levels, automated insulin delivery systems were developed and have been lifesavers to persons with diabetes. Insulin pumps have become increasingly popular over time as a method to manage diabetes once placed under the skin. Throughout the day, the insulin the pump can give small doses of insulin as basal insulin, typically set up by your healthcare professional. The patient must enter in the amount of bolus, or mealtime, insulin is required based on their personal needs. The pump is typically the size of a deck of cards and typically doses are delivered more accurately with an insulin pump. Currently there are 6 insulin pumps that are recognized by the American Diabetes Association:

• Tandem T Slim X2 with Basal-IQ
• Tandem T Slim X2 with Control-IQ
• Omnipod 5
• Omnipod DASH
• Medtronic 770G/780G
• Medtronic 630G

Amongst these, you may find pumps that requires no calibrations throughout the day, such as the Omnipod 5, or insulin capacity up to 300 units, such as the Medtronic 770G/780G.

Boston University has brought a revolutionary device to the healthcare world, one that can be considered the “next-generation technology”. After completing long and successful clinical trial , the bionic pancreas, got approved for use in patients aged 6 years and older with Type 1 diabetes. It has been billed as the “first and only automated insulin-delivery system that delivers 100% of all insulin doses”. The iLet is an artificial device that can deliver personalized insulin doses every 5 minutes, dependent upon the glucose levels and the body’s reaction to previous insulin deliveries. Patients will have an easier time managing their diabetes without the stress of constantly having to calculate their insulin doses with adjustments. Patients will also be freed of having to monitor their glucose levels, optimizing their quality of life. One of the large benefits of the iLet system compared to insulin pumps is that it independently determines changes that are required for a patient in terms of basal rates, glucose correction factors, insulin correct factors, and other regimen parameters. Users must enter their body weight into the device’s software prior to initiating the regimen during the time of first use. Allowing patients to have this new level of ease in the management of Type 1 diabetes can be vital to transforming their day-to-day life. The most reported adverse effect with the use of the iLet was hyperglycemia (43%). Currently the iLet can be configured as an insulin only, glucagon only, or insulin-glucagon dual delivery system. The pocket-sized system is deemed to be a great breakthrough device. This fully automated bionic pancreas has shown improvement of HbA1c in persons with Type 1 diabetes, per the randomized, multicenter trial.

REFERENCES:

FDA Clears iLet Bionic Pancreas System for Type 1 Diabetes. www.medpagetoday.com. Published May 19, 2023. Accessed June 21, 2023. https://www.medpagetoday.com/endocrinology/type1diabetes/104599#:~:text=The%20pump%20can%20be%20configured

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FDA Clears Bionic Pancreas Developed in BU Lab for People with Type 1 Diabetes. Boston University. Published May 24, 2023. https://www.bu.edu/articles/2023/fda-clears-bionic-pancreas-for-type-1-diabetes/

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Commissioner O of the. FDA Clears New Insulin Pump and Algorithm-Based Software to Support Enhanced Automatic Insulin Delivery. FDA. Published May 22, 2023. Accessed June 21, 2023. https://www.fda.gov/news-events/press-announcements/fda-clears-new-insulin-pump-and-algorithm-based-software-support-enhanced-automatic-insulin-delivery

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Bionic Pancreas System Safe, Cuts HbA1c in Type 1 Diabetes. www.medpagetoday.com. Published September 28, 2022. Accessed June 21, 2023. https://www.medpagetoday.com/endocrinology/type1diabetes/100956

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After the recent release of the 2023 American Diabetes Association (ADA) Standards of Care, you may be wondering whether metformin is still the one size fits all for the first line treatment of all persons with newly diagnosed type 2 diabetes. Please check on the link below to learn more. Also, if you are a primary care provider, pharmacist or pharmacy or medical learner, please submit to my YouTube channel, ReecesPiecesDiabetes.

Please follow me on Twitter (@ReecesPiecesDi), Instagram (reecespiecesdi) and You Tube (ReecesPiecesDiabetes).

As I reflect on November being National Diabetes Awareness Month, I can recall my first encounter with diabetes. I remember visiting my grandparents in Thomasville, and my grandfather would take his insulin before meals. I was rather young, curious and had really no true understanding of Diabetes!  Being inquisitive, I asked to see his diabetes medicine. In his study, he had his insulin vial and syringes sitting on top of the table. Upon seeing them, I was alarmed and scared due to my fear of my needles. I wondered how someone is able to inject themselves multiple times a day-everyday- for the rest of their life!!!

Fast forward 15 years when I began to learn about diabetes in pharmacy school – I must admit that it was much less personal and rather academic in nature (absorbing information to pass the test rather than truly understanding it).  Not until after pharmacy school did I get  up close and personal with diabetes again. I worked with a national diabetes foundation project in which I trained pharmacists to serve as diabetes coaches for employees with diabetes of a large employer in central Georgia. In this role, I also served as a diabetes coach myself. I got to know Barbara really well in this process as we were paired to work together.  We met at the local track to walk on several occasions and talk through her challenges in living with diabetes. I really began to understand what it is like to live with diabetes as I developed more of these one on one relationships and provided support.

I am like many folks who struggle with weight management and healthy eating challenges.  I have had prediabetes off and on for the last several years. My inspiration to stay on track (and get back on track at times) comes from the people with diabetes that I work with day in and day out.  I feel the pain and struggle and yet, I also bask in the joy of the achievements along the way that I experience walking side by side with each person with diabetes.  Most recently, I recall the experience of  joy as Billy lowered his hemoglobin A1c down from over 10% to 7% (a few tears were shed along the way) and an older person with diabetes finally getting the personal CGM that is compatible with their iphone. Yet, I also recall the frustration of another individual not understanding why their glucose is running 300 – 500 mg/dL after being consistently at or below 150 mg/dL (many tears were shed). My professional calling is to work alongside persons living with diabetes and educating learners about the whole person approach to managing and caring for the person living with diabetes. I honor each person living with diabetes as they face the daily challenges and victories along the way. I am inspired by each of you. 

Contributors: Alexandrea Coleman and Dion Blocker, PharmD Candidates Class of 2023, PCOM Georgia School of Pharmacy

What is diabetes? People commonly make the mistake of thinking that diabetes is only about having high blood sugar levels. Having consistently high blood sugar levels isn’t that big of a deal right? Wrong! Diabetes is a highly complicated condition. Diabetes can cause many different kinds of disturbances that affect many different organs – including the heart and kidneys. Uncontrolled diabetes is notorious for being the culprit of changes that can result in life-threatening kidney dysfunction. As you can see, protecting the kidneys should be a priority for patients with diabetes. This priority is especially important for patients who already have kidney disease. 

Don’t you wish there was a drug class that could slow down the progression of kidney disease for people with diabetes? I am way ahead of you! A class of drugs that does this already exists!

The sodium-glucose cotransporter-2 is a transporter that reabsorbs glucose and sodium in the kidneys. If this transporter is blocked, sodium and glucose are allowed to leave the kidneys in hordes; which leads to the body urinating out tons of glucose and extra water. A class of drugs was designed to target this exact action. The drugs are named the “sodium-glucose cotransporter-2 inhibitors”, or SGLT2 for short. When it comes to certain disease states, healthcare providers are always looking at a patient’s medication list to see if something they are taking is contributing to their current condition. SGLT2 is a special drug class where they actually add benefits across disease states. They are not only able to aid in the treatment of type 2 diabetes, but they have also been able to show that they can slow the progression of kidney disease in patients. They have even been shown to benefit patients that have a higher risk of having fatal heart events. 

This class of medication can provide a multitude of benefits for patients, across disease states. Prior to the release of this drug class, most diabetes therapies were targeted specifically to treat diabetes and did not add any additional benefits to other conditions the patient may currently have. In the most recent update to the ADA guidelines, you will see that patient treatment no longer goes straight to Metformin for all patients. It is actually preferred now that patients be placed on SGLT2i therapy first, if they have kidney or heart risk factors. 

Let’s meet a patient to practice and see the added benefits of SGLT2-inhibitors:

BC, a 64-year-old male, has been seen in your clinic for the treatment of his type 2 diabetes. When assessing his past medical history, you note that he also has a diagnosis of stage 3 chronic kidney disease with no other medical conditions. BC wants to discuss the medical conditions that he currently has and what he can do to improve his quality of life. He wants to get his medical conditions under control so that he can improve his life expectancy. This would be an ideal candidate for a SGLT2-inhibitor. It would not only help the patient to improve their diabetes, by increasing the amount of glucose that is being excreted in the urine, but it would also provide dual benefits and slow the progression of his current kidney disease. 

What are my options when it comes to SGLT2-inhibitors and what are the doses?

• Invokana (canagliflozin)
  • Starting dose: 100 mg once daily 
  • Maintenance dose: 300 mg once daily
    • Only titrate to this dose if the patient can tolerate the starting dose 
  • Patients with an eGFR of 45 to less than 60 mL/min/1.73m² should limit the dose to 100 mg once daily 
  • If the eGFR is less than 45 ml/min/1.73m², it is not recommended to use this medication 
• Farxiga (dapagliflozin)
  • Diabetes:
    • Starting dose: 5 mg once daily 
    • Maintenance dose: 10 mg once daily
      • Only titrate to this dose if the patient can tolerate the starting dose 
    • Not recommended for patients who have an eGFR of less than 45 mL/min/1.73m².
  • Heart failure:
    • Maintenance dose: 10 mg once daily
      • Do not need to use a starting dose 
    • No dose adjustments are needed for patients with eGFR > 30 mL/min/1.73m²
• Jardiance (empagliflozin)
  • Starting dose: 10 mg
    • May titrate up to 25 mg if the patient tolerates the starting dose 
  • Do not initiate therapy if eGFR is less than 45 mL/min/1.73m²
    • Stop therapy if eGFR is less than 45 mL/min/1.73m²
  • If a patient has a diagnosis of heart failure, therapy can be continued as long as eGFR ≥ 20 mL/min/1.73m² 
• Steglatro (ertugliflozin)
  • Starting dose: 5 mg, take in the morning and it can be taken with or without food
    • May titrate up to 15 mg, as long as the patient tolerates the starting dose 
  • Do not initiate if eGFR < 30 mL/min/1.73²
    • Not recommended for initiation in patients with eGFR 30 to 60 mL/min/1.73²   
    • Therapy should be discontinued if the patient’s eGFR is consistently between 30 to 60 mL/min/1.73²  

References: 

1. American Diabetes Association Professional Practice Committee; 11. Chronic Kidney Disease and Risk Management: Standards of Medical Care in Diabetes—2022. Diabetes Care 1 January 2022; 45 (Supplement_1): S175–S184.
2. Invokana [package insert]. Titusville, NJ: Janssen Pharmaceuticals, 2013. 
3. Farxiga [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP, 2020. 
4. Jardiance [package insert]. Indianapolis, IN: Boehringer Ingelheim Pharmaceuticals, Inc., 2016. 
5. Steglatro [package insert]. Whitehouse Station, NJ: Merck & CO., INC., 2017. 

Contributors: Yeunju Kim and Erica Wong, PharmD Candidates Class of 2023, PCOM Georgia School of Pharmacy

Sometimes when life deals you lemons, you don’t always get lemonade!  Managing your glucose levels is not always the type of daily activity that is easy to do. Bob is a 50 year old male with a past medical history of type 2 diabetes with presence of diabetes related neuropathy along with several other pain related conditions. Bob’s current medication regimen includes both basal bolus insulin regimen, as well as long-term use with opioid-pain medication and steroid injections for the treatment of pain. The increasing stress levels has contributed to a hemoglobin A1c slightly above 9%  and average daily glucose ranges from 270 mg/dL to 295 mg/dL, despite his insulin therapy.

For persons with type 2 diabetes and comorbidities that can significantly increase glucose and/or create wide variations in daily glucose levels, find themselves to be at a higher risk of diabetes-induced complications. In such persons, a continuous glucose monitoring system (CGM) is strongly preferred. CGMs, including recently FDA approved Freestyle libre 3, is typically recommended for those who have uncontrolled glucose levels, higher risk for hypoglycemia, variable deviations between discordant A1c, finger-stick readings, or suspected medication non-adherence.¹ 

Abbott’s Tiny Freestyle Libre 3 Cleared in EU. Medgadget. Mar 2020. (https://www.medgadget.com/2020/10/abbotts-tiny-freestyle-libre-3-cleared-in-europe.html)

The Freestyle Libre 3 CGM style, unlike Freestyle Libre 2, is designed to track real time glucose level automatically every minute instead of having to scan every 8 hours. Another benefit of Freestyle Libre 3 compared to other CGMs is that it is the smallest, thinnest, and most accurate 14-day continuous glucose monitoring system currently available in the market. For persons like Bob who require close monitoring of glucose to manage their type 2 diabetes, a commitment to scanning the sensor will not be an issue since Freestyle Libre 3 automatically tracks real time glucose level and shows trends using collected data. 

Comparison between Dexcom G6 vs FreeStyle Libre 2 & 3 ^2,3,4,5

Side note: Dexcom G7 is expected to be FDA approved in 2022.

References:

1. Add continuous glucose monitoring to your practice: a step-by-step guide. Aafp.org. Published March 15, 2021. Accessed June 13, 2022. https://www.aafp.org/pubs/fpm/blogs/inpractice/entry/cgm_guide.html
2. FreeStyle Libre 3 System. Freestyle.abbott. Accessed June 13, 2022. https://www.freestyle.abbott/us-en/products/freestyle-libre-3.html
3. FreeStyle Libre 2 System. Freestyle.abbott. Accessed June 13, 2022. https://www.freestyle.abbott/us-en/products/freestyle-libre-2.html
4. Dexcom. Dexcom. Accessed June 13, 2022. https://www.dexcom.com/
5. Abbott’s FreeStyle® libre 3 system receives CE Mark – features world’s smallest, thinnest sensor with best-in-class performance at the same low cost for people with diabetes. Abbott MediaRoom. Accessed June 13, 2022. https://abbott.mediaroom.com/2020-09-28-Abbotts-FreeStyle-R-Libre-3-System-Receives-CE-Mark-Features-Worlds-Smallest-Thinnest-Sensor-with-Best-in-Class-Performance-at-the-Same-Low-Cost-for-People-with-Diabetes

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).