Learning Outcomes
By the end of this section, you should be able to:
- 28.3.1 Identify the characteristics of oral diabetes drugs.
- 28.3.2 Explain the indications, actions, adverse reactions, contraindications, and interactions of oral diabetes drugs.
- 28.3.3 Describe nursing implications of oral diabetes drugs.
- 28.3.4 Explain the client education related to oral diabetes drugs.
Oral diabetes drugs are used to treat type 2 diabetes. They are ineffective with type 1 diabetes because type 1 diabetic β cells are not functioning. These drugs lower blood glucose levels in various ways, such as stimulating insulin production from β cells, decreasing insulin resistance, slowing glucose absorption from the gastrointestinal tract, and altering the release of glucose by the liver (American Diabetes Association, n.d.-a).
Sulfonylureas
Sulfonylureas are a group of diabetes drugs that bind to potassium channels on β cells and stimulate them to produce more insulin. They are effective in clients with diabetes who have functioning β cells. They are not effective in all clients with type 2 diabetes. Sulfonylureas may lose their effectiveness over time, requiring an increase in dosage (Costello et al., 2022).
Safety Alert
Sulfonylureas
Sulfonylureas should be used cautiously with beta blockers. Beta blockers can mask the early symptoms of hypoglycemia, such as tachycardia and tremors. Also, when taken with a sulfonylurea, a nonselective beta blocker can prevent the body from compensating for hypoglycemia, resulting in critically low levels especially when the client is sleeping (Costello et al., 2022; Dimakos et al., 2023).
First-Generation Short-Acting Sulfonylureas
First-generation short-acting sulfonylureas lower blood glucose levels by causing the pancreas to produce insulin. These drugs were previously used along with diet, exercise, and, at times, other diabetes drugs to control type 2 diabetes; however, they have been discontinued for use in the United States with the development of second-generation sulfonylureas (Costello et al., 2022).
Second-Generation Sulfonylureas
Second-generation sulfonylureas increase insulin secretion through the pancreatic β cells. They are used along with diet, exercise, and sometimes other diabetes drugs to control glucose levels. Second-generation sulfonylureas typically have lower dosing, a longer duration of action, and fewer side effects than first-generation sulfonylureas. These drugs are metabolized in the liver and excreted in the urine. They should be used cautiously in clients with hepatic and renal impairment. Dosage usually begins with a low dose and is increased based on the client’s glucose control needs (Costello et al., 2022).
Glipizide
Glipizide is a second-generation sulfonylurea that stimulates the pancreas to produce insulin, thereby lowering blood glucose levels. Glipizide is used along with diet and exercise to improve glucose homeostasis in adults with type 2 diabetes. Glipizide comes in tablet form and should be taken 30 minutes before the first meal of the day. It also comes in an extended-release form. The extended-release form should not be chewed, crushed, or broken and should be swallowed whole. The extended-release form should be taken with the first meal of the day.
Adverse effects of glipizide include headache, irritability, sweating, tachycardia, dizziness, nausea, blurred vision, feeling shaky, hypoglycemia, drowsiness, tremor, insomnia, myalgia, weight gain, and paresthesia. Serious adverse effects include agranulocytosis, aplastic anemia, thrombocytopenia, hepatic failure, and syndrome of inappropriate antidiuretic hormone (SIADH). Liver enzymes should be monitored closely when using this drug (National Library of Medicine, 2022b).
Glyburide
Glyburide is a second-generation sulfonylurea that stimulates the pancreas to produce insulin. Glyburide is used along with diet and exercise to control glucose levels. It comes in tablet form and is taken once or twice daily. Adverse effects include indigestion, flatulence, arthralgia (joint pain), blurred vision, dizziness, hypoglycemia, and irritability. This medication should be used cautiously with beta blockers because severe hypoglycemia may occur when they are taken together (National Library of Medicine, 2022c).
Glimepiride
Glimepiride, like glyburide and glipizide, is a second-generation sulfonylurea used along with diet and exercise to control blood glucose levels in the body. It is often used along with insulin to treat type 2 diabetes. Glimepiride comes in tablet form and is taken once daily with the first meal of the day. Adverse effects include dizziness, nausea, jaundice, upper abdominal pain, diarrhea, hypoglycemia, blurred vision, weight gain, and elevated serum alanine aminotransferase (ALT) levels (National Library of Medicine, 2022a; DailyMed, Glimepiride, 2021).
Non-Sulfonylurea Biguanides
Non-sulfonylurea biguanides are a group of oral diabetes drugs that prevent the production of glucose in the liver. They improve the body’s sensitivity to insulin and reduce the amount of glucose absorbed by the intestines. Non-sulfonylurea biguanides are used to treat type 2 diabetes (Corcoran & Jacobs, 2022).
Metformin is a non-sulfonylurea biguanide. It is used to treat type 2 diabetes along with diet, exercise, and sometimes other diabetes drugs or insulin. Metformin comes as an immediate release tablet, an extended-release tablet, and an oral solution. Adverse effects include dizziness, headache, weakness, hypoglycemia, palpitations, flushing, nausea, vomiting, diarrhea, and flatulence. Metformin should be used cautiously in older clients and in clients with renal and hepatic impairments. Clients should not drink alcohol while taking metformin (Corcoran & Jacobs, 2022).
Safety Alert
Metformin and Contrast Dye
Contrast dye can increase the risk of lactic acidosis (when lactic acid production exceeds lactic acid clearance in the body) in clients who are taking metformin and have decreased renal function. Metformin should be withheld 24 hours prior to and for 48 hours after contrast dye administration if the estimated glomerular filtration rate (eGFR) is less than 30 mL/min (Yale School of Medicine, 2022).
FDA Black Box Warning
Metformin
Lactic acidosis is a rare but potentially severe consequence of therapy with the non-sulfonylurea biguanide metformin.
Alpha-Glucosidase Inhibitors
Alpha-glucosidase inhibitors lower blood glucose levels by inhibiting enzymes such as amylase, maltase, and sucrose in the GI tract, thus delaying the digestion and intestinal absorption of carbohydrates (Akmal & Wadhwa, 2022).
Acarbose
Acarbose was the prototype alpha-glucosidase inhibitor. It delays digestion and absorption of carbohydrates to diminish the increase in blood glucose levels after meals. Acarbose is rapid acting and peaks in 1 hour. It is metabolized by the GI tract and excreted in the urine and feces. Adverse effects include nausea, vomiting, diarrhea, malabsorption, leukopenia, thrombocytopenia, and anemia. It is contraindicated for use in clients with severe renal and hepatic impairments (Feingold, 2022).
Miglitol
Miglitol slows the digestion of carbohydrates. It is used in combination with diet, exercise, and sometimes other drugs to control blood glucose levels. It is rapidly absorbed and excreted in the urine. Adverse effects include bloating, flatulence, diarrhea, and abdominal pain or cramping (Feingold, 2022).
Thiazolidinediones
Thiazolidinediones lower blood glucose levels by decreasing insulin resistance. They are referred to as “glitazones” or “insulin sensitizers” (Feingold, 2022; Eggleton & Jialal, 2023).
Pioglitazone hydrochloride is a thiazolidinedione that is used along with diet and exercise to decrease blood glucose levels. It works to enhance the body’s response to insulin, thereby decreasing glucose in the blood. Adverse effects include muscle pain, weight gain, sore throat, blurred vision, and tooth problems. Pioglitazone hydrochloride is contraindicated in those with liver impairment (Feingold, 2022).
Meglitinides
Meglitinides lower blood glucose levels by stimulating the pancreas to secrete insulin. This class of drug has the potential to produce rapid, short-lived insulin output in those with type 2 diabetes. Because of the rapid onset and short duration of action with these drugs, they should be administered 1–30 minutes prior to meals (Feingold, 2022).
Repaglinide is a meglitinide that works in clients with type 2 diabetes by closing potassium channels in the pancreatic beta cells, thereby increasing insulin secretion, which lowers glucose levels in the blood. It is absorbed through the GI tract and peaks in 1–1.5 hours. Metabolism occurs in the liver, and it is excreted in the urine and feces. Adverse effects include GI upset, upper respiratory infections, and hypoglycemia. It is contraindicated for use in those with type 1 diabetes and those with diabetic ketoacidosis (Feingold, 2022).
Dipeptidyl Peptidase 4 (DDP 4) Inhibitors
Dipeptidyl peptidase 4 inhibitors block the action of dipeptidyl peptidase 4, an enzyme that destroys incretin. Incretin helps the body produce insulin only when it is needed to reduce the excess amount of glucose being produced by the liver. DDP 4 inhibitors are used to treat type 2 diabetes (Kasina & Baradhi, 2022).
Sitagliptin
Sitagliptin is a DDP 4 inhibitor used to treat type 2 diabetes. It is rapidly absorbed, peaks in 1–4 hours, and has a 12-hour half-life. It is mainly excreted through the urine. Adverse effects include runny nose, sore throat, headache, and upper respiratory infections. Hypoglycemia may occur when used in combination with other drugs. Sitagliptin is contraindicated in those with congestive heart failure (Zhou et al., 2019).
Linagliptin
Linagliptin, like sitagliptin, is a DDP 4 inhibitor used to treat type 2 diabetes. It is rapidly absorbed and long acting. It peaks in 1.5 hours and has a 12-hour half-life. Adverse effects include bloating, skin rash, stomach pain, back pain, and joint pain. It should be used cautiously in those with hypersensitivity, exfoliative dermatitis, or bronchial hypersensitivity (Gharabaghi et al., 2022).
Selective Sodium Glucose Transporter 2 (SGLT2)
Selective sodium glucose transporter 2 drugs are used to treat clients with type 2 diabetes. SGLT2 drugs lower blood glucose levels by blocking the reabsorption of glucose in the kidneys and promoting the excretion of glucose in the urine (Padda et al., 2022).
Dapagliflozin
Dapagliflozin is an SGLT2 drug that reduces reabsorption of filtered glucose and thereby promotes urinary glucose excretion. It is rapidly absorbed and peaks in 2 hours. It is metabolized in the liver and excreted mainly in the urine. Adverse effects include increased urination, skin rash, dehydration, hypotension, back pain, and genital infections including UTIs. It is contraindicated in those with renal impairment (Dhillon, 2019).
Empagliflozin
Empagliflozin is an SGLT2 drug that is rapidly absorbed. It peaks in 1.5 hours. Empagliflozin is metabolized by the liver and excreted mainly in the urine. Adverse effects include increased urination, bladder pain, painful urination, vaginal irritation or discharge, and pain during intercourse. It is contraindicated in those with renal impairment (Sizar et al., 2022).
Fixed Combination Oral Diabetes Drugs
Fixed combination oral diabetes drug therapy may be required in the control of type 2 diabetes. Combination oral diabetes drug therapy is used when monotherapy, diet, and exercise alone cannot control blood glucose levels. Although in the past these drugs were taken as separate tablets, several fixed-dose single-tablet combinations have been manufactured (Kalra et al., 2020).
Link to Learning
New in Oral Diabetes Medicines: Non-Insulin Injectables
In this video, Lisa Kroon, a Doctor of Pharmacy, describes general treatments for glycemic control (hyperglycemia) in people with type 2 diabetes.
Glyburide-Metformin
Glyburide-metformin is a combination of a second-generation sulfonylurea and a non-sulfonylurea biguanide. It is used in conjunction with diet and exercise for clients with type 2 diabetes that was not controlled with a monotherapy diabetes drug. Dosing is a combined tablet of 1.25 mg glyburide and 250 mg metformin one to two times daily. The maximum dose is 20 mg glyburide and 2000 mg metformin daily. It is not recommended for use in children. Adverse effects include blurred vision, drowsiness, excessive hunger, headache, nausea, nervousness, sore throat, and unusual tiredness. Glyburide-metformin is contraindicated in those with severe renal and liver impairment. Those with congestive heart failure should use it cautiously because this drug may increase the risk of myocardial infarction (Shuster et al., 2020).
Sitagliptin-Metformin
Sitagliptin-metformin is a fixed-dose combination diabetes drug that combines a dipeptidyl peptidase 4 inhibitor and a non-sulfonylurea biguanide. Sitagliptin-metformin is used to treat type 2 diabetes when the diet, exercise, and monotherapy diabetes drugs were ineffective. The recommended starting dose in clients not currently treated with metformin is 50 mg sitagliptin and 500 mg metformin HCl twice daily, with gradual dose escalation recommended to reduce gastrointestinal side effects associated with metformin. The starting dose in clients already treated with metformin should provide sitagliptin dosed as 50 mg twice daily (100 mg total daily dose) and the dose of metformin already being taken. For clients taking metformin HCl 850 mg twice daily, the recommended starting dose of sitagliptin-metformin is 50 mg sitagliptin and 1000 mg metformin HCl twice daily. The maximum recommended daily dose is 100 mg of sitagliptin and 2000 mg of metformin hydrochloride (HCl). Adverse effects include diarrhea, upper respiratory tract infection, headache, nausea, vomiting, abdominal pain, hypoglycemia, EKG changes, pancreatitis, acute renal failure, myalgia, and pain in extremity (DailyMed, Sitagliptin, 2023; He et al., 2021).
Liraglutide-Insulin Degludec
Liraglutide-insulin degludec is a fixed-dose combination of liraglutide and insulin degludec. It is used to treat type 2 diabetes when diet, exercise, and drug monotherapy were ineffective. It comes in a subcutaneous pen similar to an insulin pen. The pen is a combined dose of insulin degludec 50 units and liraglutide 1.8 mg. Adult and pediatric dosing is based on the client’s blood glucose level and must be determined by the health care provider. Adverse effects include bloating, blurred vision, chills, confusion, constipation, dry mouth, headache, hives, increased hunger, lightheadedness, muscle aches, nausea, sweating, tachycardia, and trouble swallowing. It is contraindicated in those with hypoglycemia, pancreatitis, and hypersensitivity (DailyMed Victoza, Liraglutide injection, 2023).
Unfolding Case Study
Part B
Read the following clinical scenario to answer the questions that follow. This case study is a follow-up to Case Study Part A.
Alaina Sanders was diagnosed with type 2 diabetes, and the health care provider prescribed extended-release glipizide 5 mg orally and lifestyle modifications. The client returns to her health care provider’s office today for a 6-month follow-up appointment after starting drug treatment and lifestyle modifications.
Laboratory Results
Glycosylated hemoglobin
6 Months Ago
7.8%
Today
6.9%
| Vital Signs | Physical Examination | |
| Temperature: | 97.4°F |
|
| Blood pressure: | 108/72 mm Hg | |
| Heart rate: | 84 beats/min | |
| Respiratory rate: | 18 breaths/min | |
| Oxygen saturation: | 97% on room air | |
| Height: | 5'5" | |
| Weight: | 173 lb | |
Hypoglycemia Drugs
Hypoglycemia drugs raise blood glucose levels. These drugs are used to treat severe hypoglycemia and hypoglycemic reactions that are often associated with diabetes. They are used after conservative measures to treat severe hypoglycemia are ineffective (Mathew & Thoppil, 2022).
Glucagon
Glucagon is a hormone secreted by alpha (α) cells of the islets of Langerhans in the pancreas. Glucagon increases blood glucose levels by stimulating glycogen breakdown in the liver. Peak time is 15 minutes after dosing. Glucagon comes as an injectable and as a nasal spray. Adult and pediatric dosing is based on the client’s age and weight. Glucagon is used when the client is semiconscious, unconscious, or unable to ingest sugar-containing food. Blood glucose levels should be reassessed 15 minutes after administering this drug. Adverse effects include nausea, vomiting, and temporary tachycardia. Glucagon is contraindicated in clients with hypersensitivity and with known pheochromocytoma (Morris & Baker, 2022).
Diazoxide
Diazoxide is a non-diuretic benzothiadiazine and works by inhibiting insulin release from the pancreas by opening potassium channels in the beta cell membrane. It is used to treat hypoglycemia in clients with hyperinsulinemia. This drug is also a vasodilator and used to treat hypertensive emergencies. It is rapidly absorbed and highly protein bound. Diazoxide is metabolized by the liver and mainly excreted by the kidneys. The usual adult daily oral dosage is 3–8 mg/kg, divided into two or three equal doses every 8 or 12 hours. Its onset is 1 hour, and its duration is 8 hours. Adverse effects include anorexia, nausea, vomiting, abdominal pain, tachycardia, palpitations, and increased uric acid levels. Diazoxide is contraindicated in clients with a hypersensitivity to sulfonamide and thiazide diuretics (Chen et al., 2021).
Table 28.7 lists common oral diabetes drugs and typical routes and dosing for adult clients (with pediatric exception note for metformin).
| Drug | Routes and Dosage Ranges |
|---|---|
| Acarbose (Precose) |
25 mg orally 3 times daily with meals. Maximum dose: 300 mg daily. |
| Dapagliflozin (Farxiga) |
Dosage is adjusted based on estimated glomerular filtration rate (eGFR):
|
| Empagliflozin (Jardiance) |
10 mg orally once daily. Maximum dose: 25 mg daily. Data are insufficient to provide a dosage recommendation in clients who have type 2 diabetes mellitus and established cardiovascular disease with an eGFR <30 mL/min/1.73 m2 or heart failure with an eGFR <20 mL/min/1.73 m2. |
| Glipizide (Glucotrol, Glucotrol XL) |
5 mg orally daily 30 minutes before breakfast. Maximum dose: 40 mg daily. Extended release: Once daily with breakfast. |
| Glyburide/metformin (Glucovance) |
1.25 mg glyburide/250 mg metformin orally daily. Titrate 2 weeks after initial dosing up to 1.25 mg glyburide/250 mg metformin orally every 12 hours. Maximum dose: 20 mg glyburide/2000 mg metformin orally daily. |
| Liraglutide/insulin degludec (Xultrophy) |
10 units insulin degludec/3.6 mg of liraglutide subcutaneously once daily. Maximum dose: 50 units insulin degludec/1.8 mg liraglutide subcutaneously daily. |
| Metformin (Glucophage, Glucophage XR) |
Immediate release: Adults: 500–1000 mg orally twice daily. Maximum dose: 2000 mg daily. Children (the only oral diabetes drug that is safe for use in children 10–17 years of age): 500 mg orally twice daily. Maximum dose: 2000 mg daily in divided doses. Extended release: Adults: 250–500 mg once daily with evening meal; increase dose by 500 mg/week on the basis of glycemic control and tolerability. Maximum dose: 2000 mg/day. Children: Health care provider should determine dose based on body surface area and glucose target range. Oral solution: Adults and children: 500 mg/5 mL daily up to a maximum dose of 2000 mg/day. |
| Miglitol (Glyset) |
25 mg orally 3 times daily at the start of each meal. Maximum dose: 200 mg 3 times daily. |
| Pioglitazone (Actos) |
15–30 mg orally once daily. Maximum dose: 45 mg daily. |
| Repaglinide (Prandin) |
0.5–4 mg orally 3–4 times daily, 15–30 minutes before meals. Maximum dose: 16 mg daily. |
| Sitagliptin (Januvia) |
100 mg orally daily. For clients with an eGFR ≥45 mL/min/1.73 m2 to <90 mL/min/1.73 m2: No dosage adjustment required. For clients with moderate renal impairment (eGFR ≥30 mL/min/1.73 m2 to <45 mL/min/1.73 m2): 50 mg once daily. For clients with severe renal impairment (eGFR <30 mL/min/1.73 m2) or with end-stage renal disease (ESRD) requiring hemodialysis or peritoneal dialysis: 25 mg once daily. May be administered without regard to the timing of dialysis. |
| Sitagliptin/metformin (Janumet) |
Clients not currently treated with metformin: Initial dose: 50 mg sitagliptin/500 mg metformin orally twice daily with gradual escalation. Clients already treated with metformin: Initial dose: 50 mg sitagliptin twice daily and the dose of metformin already being taken. Maximum dose: 100 mg sitagliptin/2000 mg metformin orally daily. |
Adverse Effects and Contraindications
Common adverse effects of oral diabetes drugs include gastrointestinal symptoms (nausea, vomiting, diarrhea, abdominal discomfort), hypoglycemia (symptoms include dizziness, shakiness, sweating/chills, clammy skin, feeling faint, agitation, confusion, blurred or impaired vision), fluid retention, weight gain, and headache.
Contraindications include hypersensitivity to the drug or any of its components, severe kidney disorders (as most of these drugs are excreted in the urine and can further impair renal function), hepatic insufficiency (as most of these drugs are metabolized by the liver and can result in further impaired hepatic function), and disorders with fluid retention (such as heart failure and renal failure, as these drugs can cause additional fluid retention and volume overload).
Table 28.8 is a drug prototype table for oral diabetes drugs featuring metformin. It lists drug class, mechanism of action, adult and pediatric dosage, indications, therapeutic effects, drug and food interactions, adverse effects, and contraindications.
| Drug Class Non-sulfonylurea biguanide Mechanism of Action Decreases intestinal absorption of glucose and improves insulin sensitivity by increasing glucose uptake |
Drug Dosage Immediate release: Adults: 500–1000 mg orally twice daily. Maximum dose: 2000 mg daily. Children (the only oral diabetes drug that is safe for use in children 10–17 years of age): 500 mg orally twice daily. Maximum dose: 2,000 mg daily in divided doses. Extended release: Adults: 250–500 mg once daily with evening meal; increase dose by 500 mg/week on the basis of glycemic control and tolerability. Maximum dose: 2000 mg/day. Children: Health care provider should determine dose based on body surface area and glucose target range. Oral solution: Adults and children: 500 mg/5 mL daily up to a maximum dose of 2000 mg/day. |
| Indications To control hyperglycemia in those with type 2 diabetes Therapeutic Effects Decreases glucose production in the liver by reducing gluconeogenesis Reduces glucose absorption from the intestines |
Drug Interactions Alcohol Dolutegravir Ginseng Psyllium Contrast dye Food Interactions Fiber-rich foods Grapefruit juice Guar gum |
| Adverse Effects Dizziness/weakness Headache Hypoglycemia Palpitations Flushing Nausea/vomiting/diarrhea/flatulence Abdominal pain Weight loss Vitamin B12 deficiency |
Contraindications Renal and hepatic impairment Metabolic acidosis Megaloblastic anemia History of myocardial infarction Caution: Monitor closely for signs of hypoglycemic reaction; use cautiously in older clients with renal and hepatic impairments |
Nursing Implications
The nurse should do the following for clients who are taking oral diabetes drugs:
- Assess the client’s knowledge about diabetes, signs and symptoms, and treatment and clarify any gaps in knowledge.
- Monitor blood glucose levels as ordered and as needed when symptoms of hypoglycemia/hyperglycemia are present.
- Provide client teaching regarding how the drug is administered and when to call the health care provider. See below for client teaching guidelines.
Client Teaching Guidelines
The client taking an oral diabetes drug should:
- Report symptoms of hypoglycemia such as headache, nervousness, sweating, clammy skin, tremor, and tachycardia.
- Report symptoms of hyperglycemia such as increased thirst, increased urine output, hot/dry skin, sweet, fruity breath odor, and ketones in urine.
- Keep 15 grams of carbohydrates on hand in case of a hypoglycemic reaction. Orange juice, graham crackers, and hard candy are appropriate carbohydrate choices during hypoglycemia.
- Show family members and their support system how to administer glucagon during a hypoglycemic reaction if the client cannot eat or drink or is unconscious.
- Keep a blood glucose journal for tracking blood glucose levels.
- Make lifestyle modifications as directed by their health care provider, such as diet, exercise, and weight loss, to help control blood glucose levels.
The client taking an oral diabetes drug should not:
- Drink alcohol with oral diabetes agents because it may impair hepatic function.