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Diabetes Medication Update
By Constance Brown-Riggs, MSEd, RD, CDE, CDN
Over the past five years, there have been several new drugs approved by the FDA for the management of type 1 and type 2 diabetes. Compared with sulfonylureas and insulin, the newer drugs for type 2 diabetes are associated with a significantly lower risk of hypoglycemia and the promotion of weight loss.1 Three new insulins were approved for people with type 1 and type 2 diabetes—a long-acting insulin analog, a rapid-acting insulin analog, and, notably, a rapid-acting inhaled insulin. To effectively counsel clients and patients with diabetes, dietitians must stay abreast of these new medications. This article will describe the new diabetes medications that have been approved over the past several years, as well as their uses, indications, and nutrition implications.
Sodium-Glucose Cotransporter 2 Inhibitors (SGLT2)
SGLT2 inhibitors are FDA approved for use with diet and exercise to lower blood glucose in adults with type 2 diabetes. Since the approval of canagliflozin (Invokana) in 2013—the first FDA approved SGLT2 inhibitor—there have been three drugs added to this class: dapagliflozin (Farxiga), empagliflozin (Jardiance), and ertugliflozin (Steglatro).2
SGLT2 inhibitors lower blood glucose by causing the kidneys to remove glucose from the body through the urine. Historically, glucose in the urine has been a sign of poorly controlled diabetes. However, in the presence of SGLT2 inhibitors, glucose in the urine is a desired outcome.2
Dietitians will need to reeducate patients on the fact glucose in the urine is a sign that the medication is working. Patients should be instructed to take SGLT2 inhibitors before the first meal of the day.
Incretin Mimetics
Incretins mimic the action of the natural hormones in the gut: glucose-dependent insulinotropic peptide and glucagon-like peptide-1 (GLP-1). These hormones are released during nutrient absorption and increase insulin in a glucose-dependent manner. They also suppress glucagon secretion, slow gastric emptying, and enhance satiety. This class is associated with a modest degree of weight loss over two years.3
Incretins are FDA approved for the treatment of type 2 diabetes. Older drugs in this class include exenatide (Byetta and Bydureon) and liraglutide (Victoza).3
Newer drugs approved since 2014 include dulaglutide (Trulicity), lixisenatide (Adlyxin), and semaglutide (Ozempic).4 Dietitians should encourage patients to increase fluids and drink sugar-free carbonated beverages to reduce nausea associated with these drugs.
Combination Drugs and Insulin
Dapagliflozin and saxagliptin (Qtern)
Qtern combines dapagliflozin, a SGLT-2 inhibitor, and saxagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor.5,6
DPP-4 enzyme inhibitors prevent or slow down GLP-1 degradation. This raises the level of GLP-1 and causes the pancreas to produce more insulin.4
The following are the three DPP-4 inhibitors available: Sitagliptin (Januvia), saxagliptin (Onglyza), and linagliptin (Tradjenta), which are taken orally once daily, independent of meals.2 They improve after-meal hyperglycemia and don’t affect weight.5
Qtern is specifically indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes who have inadequate control with dapagliflozin or who are already treated with dapagliflozin and saxagliptin.6
Dapagliflozin + metformin hydrochloride (Xigduo XR)
Xigduo XR is a combination of dapagliflozin and metformin hydrochloride, specifically indicated as an adjunct therapy to diet and exercise to improve glycemic control in adults with type 2 diabetes when treatment with both dapagliflozin and metformin is appropriate.7
Metformin hydrochloride is a biguanide. This class of medications enhances insulin sensitivity in the muscle and decreases hepatic glucose production.2 Biguanides have the potential to decrease vitamin B12 and folate absorption, so RDs should monitor their patients’ B12 and folate levels—especially in those with anemia or peripheral neuropathy. Biguanides aren’t associated with weight gain and have the potential to promote slight weight loss.8
Patients should take Xigduo XR in the morning with food to reduce gastrointestinal upset.7
The following insulins and insulin combination drugs are associated with a risk of hypoglycemia. Therefore, dietitians must educate patients receiving these drugs on the signs, symptoms, and treatment of hypoglycemia.
Insulin glargine and lixisenatide injection (Soliqua 100/33)
Soliqua 100/33, a combination of insulin glargine, a basal insulin analog, and lixisenatide, a GLP-1 receptor agonist, is FDA approved for the treatment of inadequately controlled type 2 diabetes.9
Insulin glargine (Lantus) is FDA approved for the treatment of type 1 diabetes in adult and pediatric patients or type 2 diabetes in adult patients who require basal (long-acting) insulin for the control of elevated blood glucose. Other basal insulin types include detemir (Levemir), glargine (Basaglar), and Insulin degludec (Tresiba).
Patients treated with Soliqua 100/33 experience similar rates of hypoglycemia compared with patients treated with insulin glargine.
Insulin degludec and liraglutide injection (Xultophy 100/3.6)
Xultophy 100/3.6 is FDA approved for the treatment of inadequately controlled type 2 diabetes. Xultophy 100/3.6 is a combination of insulin degludec and liraglutide, a GLP-1 receptor agonist.10
Insulin degludec injection (Tresiba) is a basal insulin FDA approved for patients with type 1 and type 2 diabetes aged 1 and older. Tresiba reaches the bloodstream several hours after injection and tends to lower glucose levels up to 24 hours or longer.11
Xultophy 100/3.6 is specifically indicated to improve glycemic control in adults with type 2 diabetes inadequately controlled on basal insulin (less than 50 units per day) or liraglutide (less than or equal to 1.8 mg per day).10
Xultophy can be taken with or without food.
Insulin human (Afrezza)
Afrezza is a rapid-acting, inhaled insulin powder that’s FDA approved for the treatment of type 1 and type 2 diabetes. Afrezza must be used in combination with an injectable long-acting insulin, as it begins working within 12 to 15 minutes and peaks by 30 minutes.12
Insulin Aspart (Fiasp)
Fiasp is a fast-acting mealtime insulin developed to more closely match the physiological insulin mealtime response. Fiasp is FDA approved for the treatment of adults with type 1 and type 2 diabetes. Fiasp appears in the blood in approximately 2 1/2 minutes. Because of its rapid onset, Fiasp can be injected at the beginning of a meal or within 20 minutes after the start of a meal.13
— Constance Brown-Riggs, MSEd, RD, CDE, CDN, is chair of the Diabetes Care and Education Dietetic Practice Group of the Academy of Nutrition and Dietetics and author of the award-winning Diabetes Guide to Enjoying Foods of the World, a convenient guide to help people with diabetes enjoy all the flavors of the world while still following a healthful meal plan.
References
1. Montvida O, Shaw J, Atherton JJ, Stringer F, Paul SK. Long-term trends in antidiabetes drug usage in the U.S.: real-world evidence in patients newly diagnosed with type 2 diabetes. Diabetes Care. 2018;41(1):69-78.
2. Ogbru O. SGLT2 inhibitors (type 2 diabetes drugs). MedicineNet website. https://www.medicinenet.com/sglt2_inhibitors_type_2_diabetes_drug_class/article.htm
#what_are_sglt2_inhibitors. Accessed August 15, 2019. Updated July 2, 2019.
3. Hansen KB, Vilsbøll T, Knop FK. Incretin mimetics: a novel therapeutic option for patients with type 2 diabetes — a review. Diabetes Metab Syndr Obes. 2010;3:155-163.
4. FDA approved drugs by medical condition. CenterWatch website. https://www.centerwatch.com/drug-information/fda-approved-drugs/medical-conditions/D. Accessed July 25, 2019.
5. DPP-IV inhibitors. John Hopkins Medicine website. https://www.hopkinsguides.com/hopkins/view/Johns_Hopkins_Diabetes_Guide/547042
/all/DPP_IV_Inhibitors. Updated December 3, 2018. Accessed August 16, 2019.
6. Qtern (dapagliflozin and saxagliptin). CenterWatch website. https://www.centerwatch.com/drug-information/fda-approved-drugs/drug/100188/qtern-dapagliflozin-and-saxagliptin-. Accessed July 25, 2019.
7. Xigduo XR (dapagliflozin + metformin hydrochloride). CenterWatch website. https://www.centerwatch.com/drug-information/fda-approved-drugs/drug/100044/xigduo-xr-dapagliflozin--metformin-hydrochloride.
Accessed July 25, 2019.
8. American Diabetes Association. Pharmacologic approaches to glycemic treatment: Standards of Medical Care in Diabetes — 2019. Diabetes Care. 2019;42(Suppl 1):S90-S102.
9. Soliqua 100/33 (insulin glargine and lixisenatide injection). CenterWatch website. https://www.centerwatch.com/drug-information/fda-approved-drugs/drug/100178/soliqua-100-33-insulin-glargine-and-lixisenatide-injection.
Accessed July 25, 2019.
10. Xultophy 100/3.6 (insulin degludec and liraglutide injection). CenterWatch website. https://www.centerwatch.com/drug-information/fda-approved-drugs/drug/100177/xultophy-100-36-insulin-degludec-and-liraglutide-injection.
Accessed July 25, 2019.
11. Tresiba (insulin degludec injection). CenterWatch website. https://www.centerwatch.com/drug-information/fda-approved-drugs/drug/100097/tresiba-insulin-degludec-injection. Accessed July 25, 2019.
12. Afrezza (insulin human) inhalation powder. CenterWatch website. https://www.centerwatch.com/drug-information/fda-approved-drugs/drug/100014/afrezza-insulin-human-inhalation-powder. Accessed July 25, 2019.
13. Novo Nordisk receives FDA approval for Fiasp, a new fast-acting mealtime insulin. PR Newswire Cision website. https://www.prnewswire.com/news-releases/novo-nordisk-receives-fda-approval-for-fiasp-a-new-fast-acting-mealtime-insulin-300528315.html. Published September 29, 2017. Accessed August 16, 2019.