Antidiabetics

Commonly Prescribed Drugs

See Mechanism of Action of Select Antidiabetics table.

Pharmacologic Profile

General Use

Insulin is used in the management of type 1 diabetes mellitus (DM). It may also be used in type 2 DM when diet and/or oral medications fail to adequately control blood sugar. The choice of insulin preparation (rapid-acting, intermediate-acting, long-acting) depends on the degree of control desired, daily blood glucose fluctuations, and history of previous reactions. Oral agents and noninsulin injectable agents are used primarily in type 2 DM. Oral agents are used when diet therapy alone fails to control blood glucose or symptoms or when patients are not amenable to using insulin or another injectable agent. Some oral agents may be used with insulin.

General Action and Information

MECHANISM OF ACTION OF SELECT ANTIDIABETICS

DRUG	MECHANISM
Dapagliflozin and empagliflozin	Sodium-glucose co-transporter 2 (SGLT2) inhibitors: Inhibit SGLT2 in proximal renal tubules →↓ reabsorption of glucose →↑ excretion of glucose in urine
Dulaglutide, liraglutide, and semaglutide	Glucagon-like peptide-1 (GLP-1) receptor agonists: ↑ glucose-dependent insulin secretion; ↓ inappropriate glucagon secretion; slows gastric emptying
Glimepiride, glipizide, and glyburide	Sulfonylureas: stimulate endogenous insulin secretion by beta cells of the pancreas and ↑ insulin sensitivity
Linagliptin and sitagliptin	Dipeptidyl peptidase-4 (DPP-4) inhibitors: Slow inactivation of incretin hormones →↑ insulin secretion and ↓ glucagon
Insulin	↑transport of glucose into cells and promotes the conversion of glucose to glycogen
Metformin	↓hepatic glucose production and intestinal absorption of glucose; ↑ insulin sensitivity
Pioglitazone	Thiazolidinedione: ↑ insulin sensitivity
Tirzepatide	Glucose-dependent insulinotropic polypeptide (GIP) receptor and GLP-1 receptor agonist: ↑ glucose-dependent insulin secretion; ↓ inappropriate glucagon secretion; slows gastric emptying

Contraindications

Insulin: Hypoglycemia. Oral hypoglycemic agents: Hypersensitivity (cross-sensitivity with other sulfonylureas and sulfonamides may exist). Hypoglycemia. Type 1 DM. Avoid use in patients with severe kidney, liver, thyroid, and other endocrine dysfunction. Should not be used in pregnancy or lactation. DPP-4 inhibitors: Type 1 DM. GLP-1 agonists: Personal or family history of medullary thyroid carcinoma. Multiple Endocrine Neoplasia syndrome type 2. Type 1 DM. SGLT2 inhibitors: Severe renal impairment. Type 1 DM. Diabetic ketoacidosis.

Precautions

Insulin: Infection, stress, or changes in diet may alter requirements. Oral hypoglycemic agents: Use cautiously in older adults; dose ↓ may be necessary. Infection, stress, or changes in diet may alter requirements. Use sulfonylureas with caution in patients with a history of cardiovascular disease. Metformin may cause lactic acidosis. DPP-4 inhibitors: Use cautiously in patients with renal impairment, history of pancreatitis, or history of angioedema to another DPP-4 inhibitor. GLP-1 agonists: Use cautiously in patients with a history of pancreatitis, diabetic retinopathy, history of angioedema to another GLP-1 agonist, or undergoing elective surgery or procedure requiring general anesthesia or deep sedation. SGLT2 inhibitors: Moderate renal impairment or use of loop diuretics may ↑ risk of hypotension and hypovolemia. History of pancreatitis, pancreatic surgery, reduced caloric intake due to illness or surgery, surgical procedures, or alcohol abuse may ↑ risk of ketoacidosis. Peripheral arterial disease, diabetic foot infection, or osteomyelitis may ↑ risk of lower limb amputation.

Interactions

Insulin: Additive hypoglycemic effects with oral hypoglycemic agents. Oral hypoglycemic agents: Ingestion of alcohol with sulfonylureas may result in disulfiram-like reaction with some agents. Alcohol, corticosteroids, rifampin, glucagon, and thiazide and loop diuretics may ↓ effectiveness. Anabolic steroids, chloramphenicol, MAO inhibitors, most NSAIDs, salicylates, sulfonamides, and warfarin may ↑ hypoglycemic effect. Beta blockers may produce hypoglycemia and mask signs and symptoms of hypoglycemia. DPP-4 inhibitors and GLP-1 agonists: Use with insulin or sulfonylureas may ↑ hypoglycemic effect. SGLT2 inhibitors: Use with insulin or sulfonylureas may ↑ hypoglycemic effect. NSAIDs, diuretics, ACE inhibitors, or ARBs may ↑ risk of acute kidney injury.

Nursing Implications

Assessment

Observe patient for signs and symptoms of hypoglycemic reactions.
Metformin and pioglitazone do not cause hypoglycemia when taken alone but may ↑ the hypoglycemic effect of other hypoglycemic agents.
Patients who have been well controlled on metformin but develop illness or laboratory abnormalities should be assessed for ketoacidosis or lactic acidosis. Assess serum electrolytes, renal function, ketones, glucose, and, if indicated, blood pH and lactate and pyruvate levels. If either form of acidosis is present, discontinue metformin immediately and treat acidosis.
For SGLT2 inhibitors, monitor for signs and symptoms of volume depletion (dizziness, feeling faint, weakness, orthostatic hypotension) after initiating therapy, especially in older adults and patients with renal impairment, low systolic BP, or on diuretics. Monitor for signs/symptoms of urinary tract infection during therapy. Monitor for ketoacidosis, especially during prolonged fasting for illness or surgery.
Lab Test Considerations: Serum glucose and A1c should be monitored periodically throughout therapy to evaluate effectiveness of treatment.

Implementation

Patients stabilized on a treatment regimen who are exposed to stress, fever, trauma, infection, or surgery may require sliding scale insulin. Withhold oral hypoglycemic agents and reinstitute after resolution of acute illness.
Discontinue SGLT2 inhibitors ≥3 days before surgery; therapy can be resumed once patient is clinically stable following surgery and has resumed oral intake.
Insulin: Available in different types and strengths and from different species. Check type, species, source, dose, and expiration date with another licensed nurse. Do not interchange insulins without physician's order. Use only insulin syringes to draw up dose. Use only U100 syringes to draw up insulin lispro dose.

Patient/Family Teaching

Explain to patient that medication controls hyperglycemia but does not cure diabetes. Therapy is long term.
Review signs of hypoglycemia and hyperglycemia with patient. If hypoglycemia occurs, advise patient to take a glass of orange juice or 2–3 teaspoons of sugar, honey, or corn syrup dissolved in water, and notify health care provider.
Encourage patient to follow prescribed diet, medication, and exercise regimen to prevent hypoglycemic or hyperglycemic episodes.
Instruct patient in proper testing of serum glucose and ketones.
Advise patient to notify health care provider if nausea, vomiting, or fever develops; if unable to eat usual diet; or if blood glucose levels are not controlled.
Advise patient to carry sugar or a form of glucose and identification describing medication regimen at all times.
Insulin is the recommended method of controlling blood glucose during pregnancy.
Insulin: Instruct patient on proper technique for administration; include type of insulin, equipment (syringe and cartridge pens), storage, and syringe disposal. Discuss the importance of not changing brands of insulin or syringes, selection and rotation of injection sites, and compliance with therapeutic regimen.
Metformin: Explain to patient the risk of lactic acidosis and the potential need for discontinuation of metformin therapy if a severe infection, dehydration, or severe or continuing diarrhea occurs or if medical tests or surgery is required.
SGLT2 inhibitors: Advise patient to notify health care provider immediately if new pain or tenderness, sores or ulcers, or infections involving the leg or foot occur and to immediately seek care if pain or tenderness, redness, or swelling of the genitals or area from the genitals back to the rectum, along with a fever above 100.4°F or malaise, occur.