A nurse is caring for a client who has diabetes mellitus and is taking glyburide

In the year 2018, there was an estimated 34.2 million Americans (roughly 10.5% of the population) suffered from Type 2 Diabetes Mellitus (T2DM). An additional 1.6 million Americans suffer from Type 1 Diabetes Mellitus (T1DM). It goes without saying that the number of clients who present with diabetes is rapidly rising – leading to a variety of serious health complications including heart disease and hypertension.

Fortunately, scientific advancements have dramatically improved the outcomes of clients suffering from T1DM as well as T2DM. Without the invention of insulin, T1DM clients and those with virtually no endogenous insulin production, would not be able to live for very long. Over the past few decades, oral and injectable therapies have been developed that enable T2DM clients to live independently of insulin for potentially a lifetime.

Indications for Diabetic Drugs

Diabetic drugs are only indicated for clients with advanced diabetes. This includes all clients with T1DM as their insulin production is null – as well as T2DM clients with chronically elevated blood sugar levels. However, one key exception to know is that metformin may be prescribed to clients with prediabetes, a condition where blood sugar levels are above normal but not so much to reach the diagnosis of T2DM.

• MOA:
  • Regular
    • Onset: 30 minutes
    • Peak:  2-4 hours
    • Duration: 5-8 hours
  • Rapid Acting:
    • Onset: 3-15 minutes
    • Peak:  45-75 hours
    • Duration: 2-4 hours
  • Intermediate (NPH):
    • Onset: 2 hours
    • Peak: 4-12 hours
    • Duration: 8-18 hours
  • Long Acting:
    • Onset: 2 hours
    • Peak: 3-9 hours (insulin detemir only)
    • Duration: ~ 24 hours
  • Side Effects:
    • Hypoglycemia: Injecting too much insulin or insulin without carbohydrate intake can lead to hypoglycemia defined as blood glucose (BG) < 70 mg/dL. Signs and symptoms include shaking, irritability, loss of focus.
    • Weight gain
    • Injection site reactions
  • Precautions
    • Avoid sliding scale insulin as this can increase the risk of hypoglycemia
    • Taking insulin with other diabetic medications (e.g. sulfonylureas) may increase the risk of hypoglycemia
  • Nursing Considering:
    • Injection technique for new insulin users:

• • • • Insulin can be injected into the abdominal wall, leg, arm, or buttock.
      • When changing from one site to another the speed of absorption of insulin may be different (e.g. the abdominal to the leg) clients should avoid changing the general site of injection and alternate on that spot. (e.g. rotating injection site on the abdomen)
      • It is recommended that clients alternate the site of injection to avoid scarring and adverse effects.
      • The pens need to be primed before use to ensure proper insulin dosage is administered.
      • When injecting insulin prior to meals it is imperative that the client remembers to eat to avoid hypoglycemia.

• • • • Signs and symptoms include shaking, irritability, loss of focus.
      • Generally, clients with hypoglycemia (BG < 70) can be managed by taking either glucose tablets or by eating and drinking carbs (1 serving of juice, candy, fruit)
      • The goal is to consume 15 grams of carbs every 15 minutes until resolution of hypoglycemia (> 70 mg/dL)
      • Clients who are comatose or not alert may require an administration of glucagon (more common for T1DM) to raise blood sugars
      • Severe hypoglycemia may warrant a hospital visit
• Common Key Generics (Brand):
  • Regular:
  • Rapid-Acting:
    • Lispro (Humalog)
    • Aspart (Novolog)
    • Glulisine (Apidra)
  • Intermediate (NPH)
  • Long acting
    • Insulin glargine (Basaglar, Lantus, Toujeo)
    • Insulin detemir (Levemir)
    • Insulin degludec (Tresiba)

• MOA:
  • Decreases hepatic glucose production
  • Decreases intestinal absorption of glucose
  • Improves insulin sensitivity
• Side Effects:
  • GI Upset
  • Weight gain/loss
  • Lactic acidosis
• Precautions:
  • Black box warning: Risk of lactic acidosis resulting in death. Risk factors include renal impairment, concomitant use of certain drugs (e.g. topiramate), > 65 years old, excess alcohol intake.
• Nursing Considering:
  • This is the preferred 1st line treatment for clients with T2DM
  • Clients may need to be titrated up on this medication to mitigate adverse effects
  • Avoid in chronic kidney disease (eGFR < 45)
• Common Key Generics (Brand)

• MOA:
  • Mimics glucagon-like peptide 1 (GLP-1) hormone
  • Binds to GLP-1 receptors stimulating glucose-dependent insulin release
  • Delays gastric emptying – increasing satiation
• Side Effects:
  • Weight loss
  • Increased satiation (fullness)
  • Acute pancreatitis
  • Injection site reactions
• Precautions
  • Avoid in clients with pancreatitis
• Nursing Considering:
  • This may be considered prior to starting clients on insulin in order to reduce A1c when oral diabetic medications are inadequate.
  • These medications are associated with cardiovascular benefits – clients with cardiovascular disease may be good candidates for these medications.
  • Some of these medications may be unsafe in clients with severe renal disease
  • Clients with potential adherence issues should avoid GLP-1 agonists that require daily administration (e.g. liraglutide, exenatide)
  • Currently most of these medications are administered via subcutaneous injection (Rybelsus) was a recently approved oral formulation.
• Common Key Generics (Brands)
  • Liraglutide (Saxenda)
  • Exenatide (Byetta)
  • Dulaglutide (Victoza)
  • Semaglutide (Ozempic, Rybelsus)

• MOA:
  • Prevents DPP-4 enzymes from breaking down the GLP-1 hormone
• Side Effects:
  • Weight neutral
  • Acute pancreatitis
  • Hepatic dysfunction
  • Serious skin reactions (vildagliptin, saxagliptin)
• Nursing Considering
  • These medications should be used with caution in clients with renal disease.
• Common Key Generics (Brands)
  • Saxagliptin (Onglyza)
  • Sitagliptin (Januvia)
  • Linagliptin (Trajenta)

• MOA:
  • Stimulates insulin release in pancreatic beta cells
• Side Effects:
  • Hypoglycemia: These medications stimulate the release of insulin regardless of glucose intake. Taking alongside insulin dramatically increases hypoglycemic risk.
  • Weight gain
  • Sulfa allergies
  • Photosensitivity
• Precautions:
  • Sulfa moiety contained in these compounds – avoid these medications in clients with sulfa allergies
  • Increased risk of hypoglycemia in clients with chronic kidney disease
• Nursing Considering:
  • Hypoglycemia is less common with glipizide
  • Use with caution in clients on insulin
  • Use with caution in clients with “sulfa allergies”
  • Use with caution in clients with severe renal disease
  • Common Key Generics (Brands)
  • Glyburide (Glynase)
  • Glipizide (Glucotrol)
  • Glimepiride (Amaryl)

• MOA:
  • Increase insulin sensitivity by acting on adipose tissue
  • Increases musculoskeletal glucose utilization
  • Decreases glucose production in the liver
• Side Effects:
  • Weight gain
  • Fluid retention – heart failure exacerbation
  • Macular edema
• Precautions:
  • Increased risk of myocardial infarction and cardiovascular death – avoid in heart failure clients.
• Nursing Considering:
  • Avoid these medications in heart failure
  • These medications do cause weight gain
• Common Key Generics (Brands)
  • Pioglitazone (Actos)
  • Rosiglitazone (Avandia)

• MOA:
  • Inhibits SGLT2 to reduce the reabsorption of glucose by up to 90% – promoting the excretion of glucose from the body.
• Side Effects:
  • Weight loss
  • Hypotension
  • Acute kidney injury
  • Increased risk of bone fracture
  • Diabetic ketoacidosis
• Precautions
  • Avoid in clients with increased risk of fractures (e.g. osteoporosis)
  • Avoid in clients who are prone to diabetic ketoacidosis
  • Avoid in clients who have frequent urinary tract infections
• Nursing Considering:
  • These medications are associated with cardiovascular benefits – making candidates with advanced cardiovascular disease a good candidate for these medications.
  • These medications increase the risk of urinary tract infections (primarily yeast infections)
  • Avoid in clients with poor kidney function
• Common Key Generics (Brands)
  • Canagliflozin (Invokana)
  • Dapagliflozin (Farxiga)
  • Empagliflozin (Jardiance)

• Insulin is always indicated in clients with T1DM and tends to be a treatment for progressed T2DM where oral medications or GLP-1 injections are inadequate for A1C reduction.
• Clients with T1DM are primarily treated with insulin – oral diabetic medications are ineffective as their pancreatic insulin production is null.
• Insulin and sulfonylureas both increase the risk of hypoglycemia – which can be severe and may potentially lead to death.
• Metformin is often the first-line treatment for clients with T2DM and is a potential treatment for clients with prediabetes.
• Many diabetes medications need to be used with caution in clients with advanced renal disease.
• GLP-1 agonists may sometimes be used instead of insulin as a first-line injectable therapy for clients with T2DM
• Many diabetes medications can increase weight gain – consider medications associated with weight loss properties in obese and overweight clients (e.g. GLP-1 agonists, SGLT2 inhibitors).

Diabetes is a complex and chronic disease that affects millions of Americans every day. Diabetes increases the risk of having cardiovascular diseases including hypotension, heart disease, and for having CV events (e.g. MI, stroke). There are many key considerations to keep in mind when treating clients with diabetes as there are many kinds of medications with various side effect profiles.

It’s important to have a firm understanding of diabetes medications as their prevalence is rapidly increasing every year for Americans today. Hopefully this NCLEX® Review of Diabetic Drugs aids in the study of diabetes and in your practice down the line.

References

1. Statistics About Diabetes. Statistics About Diabetes | ADA. https://www.diabetes.org/resources/statistics/statistics-about-diabetes. Accessed April 21, 2020.
2. American Diabetes Association. 2. Classification and Diagnosis of Diabetes: Standards of Medical Care in Diabetes-2020. Diabetes Care. https://care.diabetesjournals.org/content/43/Supplement_1/S14.figures-only. Published January 1, 2020. Accessed April 21, 2020.
3. American Diabetes Association. 9. Pharmacologic Approaches to Glycemic Treatment: Standards of Medical Care in Diabetes-2020. Diabetes Care. https://care.diabetesjournals.org/content/43/Supplement_1/S98. Published January 1, 2020. Accessed April 21, 2020.
4. Weinstock, RS. General principles of insulin therapy in diabetes mellitus. In: Post T, ed. UpToDate. Waltham, MA.: UpToDate; 2020. www.uptodate.com. Accessed April 21st, 2020.
5. Metformin: Drug Information. In: Post T, ed. UpToDate. Waltham, MA.: UpToDate; 2020. www.uptodate.com. Accessed April 21st, 2020.
6. Dungan K, DeSantis A. Glucagon-like peptide 1 receptor agonists for the treatment of type 2 diabetes mellitus. In: Post T, ed. UpToDate. Waltham, MA.: UpToDate; 2020. www.uptodate.com. Accessed April 21st, 2020.
7. Dungan K, DeSantis A. Dipeptidyl peptidase 4 (DPP-4) inhibitors for the treatment of type 2 diabetes mellitus. In: Post T, ed. UpToDate. Waltham, MA.: UpToDate; 2020. www.uptodate.com. Accessed April 21st, 2020.
8. Wexler D. Sulfonylureas and meglitinides in the treatment of type 2 diabetes mellitus. In: Post T, ed. UpToDate. Waltham, MA.: UpToDate; 2020. www.uptodate.com. Accessed April 21st, 2020.
9. Inzucchi S, Lupsa B. Thiazolidinediones in the treatment of type 2 diabetes mellitus. In: Post T, ed. UpToDate. Waltham, MA.: UpToDate; 2020. www.uptodate.com. Accessed April 21st, 2020.