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.
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
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
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.
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.
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.
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.
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.
Diabetes technology is exploding new innovations coming fast. The recent FDA approval of Bigfoot Biomedical’s smart insulin cap which allows for on demand insulin dose recommendation. The system is made up of a smart pen cap (compatible with all U.S. brands of rapid and long acting disposable insulin pens), mobile app and integration with Freestyle Libre 2 continuous glucose monitor sensor. What an innovation! To learn more, please click below.
A novel medication, imeglimin, for type 2 diabetes has shown promising results in lowering hemoglobin A1c and fasting glucose. Its mechanism of action addresses excessive release of glucose from liver, decreased uptake of glucose by muscle tissue and increase death of beta cells. It has been in development for a few years. The most recent study, TIMES 1, assessed the safety, efficacy (how well does imeglimin work in lowering hemoglobin A1c) and tolerability (can persons taking the drug tolerate the drug) of imeglimin 1000 mg taken twice daily in persons not at goal hemoglobin with diet and exercise. The study results were promising in imeglimin’s ability to lower hemoglobin A1c. To learn more, please click on link below.
Hypoglycemia is serious business. Timely treatment is essential. We now have an additional option for treatment of hypoglycemia. Dasiglucagon (brand name Zegalogue) is a human glucagon analogue that is approved for treatment of severe hypoglycemia in persons with diabetes 6 years of age and older. The three studies assessing efficacy of dasiglucagon included children 6 – 17 years old and adults with type 1 diabetes. On average, the median time to glucose recovery was 10 minutes across the three studies. To learn more about this new option for treatment of hypoglycemia, please click below.
Contributor: Quynh Nguyen, PCOM Georgia PharmD Candidate Class of 2022
CB, 50 year old female with 10 year history of type 2 diabetes, recently shared her frustration of struggling to lose weight. While her A1c is below 7%, the scale will not budge. She feels like her diabetes medications are working great in lowering her blood glucose but not so positive impact on her weight. CB is not alone in her frustration as one of the frustrations that I most commonly hear from persons taking insulin is the weight gain. Often, glucagon like peptide 1 (GLP-1) agonists can be an alternative to insulin as this class of drugs effectively lowers glucose and body weight as well as protects the heart. Within the GLP-1 agonist class, semaglutide has been shown in clinical trials to have the greatest body weight reduction. Recently, results from two clinical trials, STEP 1 and 2, have shed additional light on the weight loss benefits of semaglutide. In both trials, life management (dietary and physical activity), a vital foundation, was combined with semaglutide.
STEP 1 study used a combination approach of lifestyle management along with once-weekly 2.4mg of semaglutide for weight loss in obese patients. In this study, a total of 1,961 adults who had a body mass index (BMI) of 30 or higher, or those with a BMI of 27 or greater with at least one weight-related disease (hypertension, liver disease, various cancers) were enrolled in this trial. Semaglutide was initiated at 0.25mg once weekly for the first four weeks, and then the dose increased every four weeks until the target dose of 2.4mg was reached. All adults in the study received lifestyle counseling (dietary and physical activity management). Data indicates within the first four weeks of initial treatment, those receiving semaglutide had more than a 2% reduction in their body weight, and continued losing weight the remainder of the 68 week trial. Furthermore, about 70% of those receiving semaglutide and lifestyle management were able to lose 10% of their weight, and about 50% were able to lose 15% of their body weight. STEP 1 study showed that in total, the adults on semaglutide treatment lost an average of 33.7 lb by the end of 68 weeks. Overall, the study provided promising results for those who want to lose weight. An average weight loss of 14.9% was achieved for those receiving semaglutide 2.4 mg and lifestyle management, versus the 2.4% of those on lifestyle management only. These promising results must be balanced with mild to moderate side effects of nausea, diarrhea, vomiting, and constipation.
STEP 2 study was similar to STEP 1 in using a combination approach of lifestyle management and semaglutide 2.4 mg once weekly except in persons with type 2 diabetes and BMI of at least 27. This STEP 2 trial included 1,210 patients with diabetes who had a BMI of at least 27, from all across the globe ranging from North and South Americas, Europe, Middle East, South Africa, and Asia. There were three different groups for this trial: one group receiving the higher dose of semaglutide which was 2.4mg, a second group receiving 1.0mg of semaglutide, and the last group, not receiving any dose of semaglutide. All three groups received lifestyle modification counseling. The two groups receiving the semaglutide began with 0.25mg weekly dose, and then the dose was increased until the target dose of 2.4 mg was reached. The semaglutide groups lost an average of 9.6% of their initial starting body weight compared to the 3.4% for those not receiving semaglutide. After 68 weeks, those receiving semaglutide 2.4 mg once weekly had a five-fold higher chance of achieving at least 5% body weight reduction versus those who did not receive semaglutide. Furthermore, about 69% of those on the higher dose (2.4mg) had improvements in their overall health including waist circumference, blood pressure, blood glucose, and physical functioning. Side effects of semaglutide were similar in STEP 1 and 2. Higher dose (2.4 mg) semaglutide provided great weight loss results for those with diabetes and BMI at 27 or higher.
The results of these trials revealed the effectiveness of using semaglutide 2.4mg weekly for weight loss, in those with and without diabetes who have a BMI at 27 or higher. As a result of these trials, NovoNordisk has submitted an application to the FDA for weight reduction indication in those with and without diabetes for the 2.4 mg dosage of semaglutide. So be on the lookout for this as a future option for weight loss for those with or without diabetes.
Back to CB, she and I discussed her trying semaglutide once weekly in place of her daily sitagliptin. When she followed up, she was pleasantly surprised to see the scale finally moved in the right direction.
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