Oral Antidiabetic Agents PDF

11/20/23, 5:29 PM Realizeit for Student Oral Antidiabetic Agents Oral antidiabetic agents may be effective for patients who have type 2 diabetes that cannot be treated effectively with MNT and exercise alone. In the United States, oral e second-generation sulfonylureas, biguanides, alpha-glucosida...

11/20/23, 5:29 PM Realizeit for Student Oral Antidiabetic Agents Oral antidiabetic agents may be effective for patients who have type 2 diabetes that cannot be treated effectively with MNT and exercise alone. In the United States, oral e second-generation sulfonylureas, biguanides, alpha-glucosidase inhibitors, nonsulfonylurea insulin secretogogues (meglitinides, phenylalanine derivatives), thiazolidinediones (glitazones), dipeptide peptidase-4 (DPP-4) inhibitors, glucagonlike peptide-1 receptor agonists (GLP-1), and sodium-glucose cotransporter 2 (SGL-2) inhibitors (see agents includantidiabetic Table 46-5). The thiazolidinediones are a class of oral antidiabetic medications that reduce insulin resistance in target tissues, enhancing insulin action without directly stimulating insulin secretion. Secondgeneration sulfonylureas and meglitinides are insulin secretagogues (Keresztes & Peacock-Johnson, 2019). Patients must understand that oral agents are prescribed as an addition to (not a substitute for) other treatment modalities, such as MNT and exercise. The use of oral antidiabetic medications may need to be halted temporarily and insulin prescribed if hyperglycemia develops that is attributable to infection, trauma, or surgery. See later section on glycemic control in the patient who is hospitalized. Because mechanisms of action vary (see Fig. 46-4), effects may be enhanced with the use of a multidose, or more than one medication (ADA, 2020). A combination of oral agents with insulin, usually glargine at bedtime, has also been used as a treatment for some patients with type 2 diabetes. Insulin therapy may be used from the onset for newly diagnosed patients with type 2 diabetes who are symptomatic and have high blood glucose and A1C levels (ADA, 2020). Other Pharmacologic Therapy https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IX2deLl%2f4FdfKSHmHSZ7peJYyAcbNSqCsVXJC0jIBoV… 1/23 11/20/23, 5:29 PM Realizeit for Student Additional medications are available for use in the pharmacologic management of diabetes. These injectables are adjunct therapies, not a substitute for insulin if insulin is required to control diabetes. Pramlintide, a synthetic analogue of human amylin, a hormone that is secreted by the beta cells of the pancreas, is approved for treatment of both type 1 and type 2 diabetes (Comerford & Durkin, 2020). It is used to control hyperglycemia in adults who have not achieved acceptable levels of glucose control despite the use of insulin at mealtimes. It is used with insulin, not in place of insulin. It acts to slow the rate at which food leaves the stomach and reduces appetite (Comerford & Durkin, 2020). The goal of therapy is to minimize fluctuations in daily glucose levels and provide better glucose control. Pramlintide must be injected subcutaneously 2 in from an insulin injection site (Comerford & Durkin, 2020). Patients are instructed to monitor their blood glucose levels closely during the initial period of use of pramlintide. Sulfonylureas The sulfonylureas are the oldest and largest group of oral agents used in patients living with type 2 diabetes. However, they are not commonly prescribed due to the increased risk of hypoglycemia. The sulfonylureas stimulate insulin secretion in patients who still have some beta cell production in the pancreas. Second-generation sulfonylureas have largely replaced first-generation sulfonylureas (e.g., chlorpropamide, tolazamide, tolbutamide). Glyburide (Glynase) is the prototype sulfonylurea. It is chemically related to sulfonamide antibacterial drugs. Pharmacokinetics After oral administration, glyburide is well absorbed and more than 90% bound to plasma proteins. The drug is metabolized to inactive metabolites in the liver. These products are excreted mainly by the kidneys; however, any whole drug is excreted about equally in urine and bile. Action Glyburide lowers blood glucose mainly by increasing secretion of insulin. It may also increase peripheral use of glucose, decrease production of glucose in the liver, increase https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IX2deLl%2f4FdfKSHmHSZ7peJYyAcbNSqCsVXJC0jIBoV… 2/23 11/20/23, 5:29 PM Realizeit for Student the number of insulin receptors, and alter postreceptor actions to increase tissue responsiveness to insulin. Because the drug stimulates pancreatic beta cells to produce more insulin, it is effective only when functioning pancreatic beta cells are present. Use Health care professionals use glyburide in combination with diet to lower blood sugar in patients with type 2 diabetes mellitus. It is usually necessary to start with a low dosage and increase it gradually until the fasting blood glucose level is 110 mg/dL or less. The lowest dose that achieves normal fasting and postprandial blood sugar levels is recommended. Use in Older Adults Older adults tend to be more sensitive to glyburide. In addition, older adults may have other disease states and may take other drugs that complicate management of diabetes. In addition, hypoglycemia is a concern. Drugs with a short duration of action and inactive metabolites are considered safer, especially in elderly people with impaired liver or kidney function. Therapy usually begins with a low dose, which is then increased or decreased according to blood glucose levels and clinical response. Use in Patients With Renal Impairment The kidneys are mainly responsible for excretion of metabolites, and renal impairment may lead to accumulation and hypoglycemia. Therefore, use of glyburide requires caution, with close monitoring of renal function, in patients with mild to moderate renal impairment. Use in severe renal impairment is contraindicated. Renal insufficiency may increase risks of adverse effects with oral hypoglycemic drugs, thereby increasing dosage requirements. Use in Patients With Hepatic Impairment Caution is warranted with use of glyburide, and monitoring of liver function is necessary. Metabolism of glyburide takes place in the liver, and hepatic impairment may result in higher serum drug levels and inadequate release of hepatic glucose in response to hypoglycemia. Glyburide may cause hypoglycemia in patients with liver disease. Adverse Effects The main adverse effect is hypoglycemia. Contraindications https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IX2deLl%2f4FdfKSHmHSZ7peJYyAcbNSqCsVXJC0jIBoV… 3/23 11/20/23, 5:29 PM Realizeit for Student Contraindications include hypersensitivity to sulfa-based medications as well as sensitivity to glyburide itself. Other contraindications include severe renal or hepatic impairment. Caution is necessary with pregnancy, lactation, pituitary, or thyroid disorders. Nursing Implications In the event of high stress such as infections, surgery, or trauma, a change to insulin therapy may be warranted. In the event of severe hypoglycemia, it is necessary to administer IV glucose. Preventing Interactions Drugs may interact with glyburide, increasing or decreasing its effects. Some herbs may increase its effects. It is extremely important that the patient inform the health care provider of all newly prescribed medications so that the patient and caregivers can be prepared to monitor for side effects related to other drugs. Administering the Medication Patients should take glyburide before breakfast in the morning or in divided doses before meals if the patient experiences gastric distress. https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IX2deLl%2f4FdfKSHmHSZ7peJYyAcbNSqCsVXJC0jIBoV… 4/23 11/20/23, 5:29 PM Realizeit for Student Drug Interactions may occur when oral antidiabetic medications are combined with Corticosteroids (systemic and inhaled) resulting in hyperglycemia and when combined with Insulin hypoglycemia may result. Alpha-Glucosidase Inhibitors Alpha-glucosidase inhibitors inhibit alpha-glucosidase enzymes (e.g., sucrase, maltase, amylase) in the GI tract, thereby delaying digestion of complex carbohydrates into glucose and other simple sugars. Acarbose (Precose), the prototype alpha-glucosidase inhibitor, is known best for improving glycosylated hemoglobin levels. The drug is obtained through the fermentation process of microorganisms. Because acarbose does not enhance insulin, it works best when given with a sulfonylurea to control blood glucose levels. https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IX2deLl%2f4FdfKSHmHSZ7peJYyAcbNSqCsVXJC0jIBoV… 5/23 11/20/23, 5:29 PM Realizeit for Student Pharmacokinetics Acarbose has a rapid onset of action and peaks in 1 hour. The drug is metabolized by the digestive enzymes and intestinal bacteria in the GI tract. It is minimally distributed and excreted in the urine and feces. Action and Use Acarbose works to delay the digestion of carbohydrates to diminish the increase in blood glucose after meals. It may be necessary to combine acarbose with insulin or an oral agent, usually a sulfonylurea. Low initial doses and gradual increases decrease GI upset (e.g., bloating, diarrhea) and promote patient adherence. Patients taking acarbose should continue their diet, exercise, and blood glucose testing routines. Acarbose does not alter insulin secretion or cause hypoglycemia. Use in Older Adults Some older adults have other complex diseases such as congestive heart failure, for which they may take digoxin. Acarbose can decrease digoxin levels, and patients who take both drugs need close monitoring. In addition, aging adults may have fat loss, resulting in weight reduction. In adults who weigh less than 60 kg, it is necessary to decrease the maximum dosage. Use in Patients With Renal Impairment Alpha-glucosidase inhibitors, which are excreted by the kidneys, accumulate in patients with renal impairment. However, dosage reduction is not helpful because the drugs act locally within the GI tract. Adverse Effects There are no serious adverse effects of acarbose. However, acarbose can cause gastric upset because the drug is metabolized in the GI tract. It also has the potential to produce leukopenia, thrombocytopenia, and anemia. Contraindications Contraindications to acarbose include hypersensitivity, DKA, hepatic cirrhosis, inflammatory or malabsorptive intestinal disorders, and severe renal impairment. Nursing Implications https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IX2deLl%2f4FdfKSHmHSZ7peJYyAcbNSqCsVXJC0jIBoV… 6/23 11/20/23, 5:29 PM Realizeit for Student Preventing Interactions As mentioned previously, acarbose can decrease digoxin levels, and thus, patients taking digoxin require close monitoring. Certain drugs may decrease the effects of acarbose. The herbs that interact with acarbose are the same as those that may affect other antidiabetic agents. Administering the Medication People should take acarbose at the beginning of each meal so that it is present in the GI tract with food and able to delay digestion of carbohydrates. Assessing for Therapeutic and Adverse Effects After acarbose administration, the increase in blood glucose levels after a meal is smaller. The nurse assesses the patient’s response to the medication—diminished blood glucose levels without signs and symptoms of hypoglycemia. The nurse also assesses for GI effects such as diarrhea, abdominal pain, and flatulence. He or she should assess the complete blood (cell) count for leukopenia, thrombocytopenia, and anemia. Biguanide The only drug available in this class is the prototype metformin (Fortamet, Glucophage, Glucophage XR, Glumetza, Riomet). Experts prefer to call it an antihyperglycemic rather than a hypoglycemic because it does not cause hypoglycemia, even in large doses, when used alone. Pharmacokinetics Absorption of metformin occurs in the small intestine, and it circulates without binding to plasma proteins. The drug has a serum half-life of 1.3 to 4.5 hours. It is not metabolized in the liver and is excreted unchanged in the urine. Action Metformin reduces the production of glucose by the liver. It also decreases the intestinal absorption of glucose to increase insulin sensitivity. This action increases the uptake of https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IX2deLl%2f4FdfKSHmHSZ7peJYyAcbNSqCsVXJC0jIBoV… 7/23 11/20/23, 5:29 PM Realizeit for Student glucose, thus enhancing its utilization to produce energy. Use People may take metformin alone or in combination with insulin or other oral agents. Prescribers widely order it as the initial drug in newly diagnosed type 2 diabetes, mainly because it does not cause the weight gain associated with most other oral agents. Authorities consider metformin to be weight neutral and ideal for overweight people with type 2 diabetes, who have been known to lose weight on this medication, further improving insulin sensitivity. Use in Older Adults Dosage titration to the maximum amount recommended for younger adults is not appropriate for older adults. Contraindications to use of metformin in older adults often include cardiovascular disorders that increase risks of fluid retention and congestive heart failure. A BLACK BOX WARNING ♦ for metformin states that patients 80 years of age or older should not take the drug because of the risk of lactic acidosis. Use in Patients With Renal Impairment With metformin, periodic tests of renal function are necessary for determining dosages. Assessment of renal function should occur before starting the drug and at least annually during long-term therapy. It is essential to discontinue the metformin if renal impairment occurs or if serum lactate increases. As with other oral hypoglycemic drugs, patients taking this drug should continue their diet, exercise, and blood glucose testing regimens. Parenteral radiographic contrast media containing iodine (e.g., Cholografin, Hypaque) may cause renal failure and have been associated with lactic acidosis in patients receiving metformin. It is important to discontinue metformin at least 48 hours before diagnostic tests are performed with these materials and resume the drug at least 48 hours after the tests are done and tests indicate that renal function is normal. Use in Patients With Hepatic Impairment Metformin is not recommended for use in patients with clinical or laboratory evidence of hepatic impairment because risks of lactic acidosis may be increased. Adverse Effects The primary adverse effect of metformin is lactic acidosis. Other adverse effects include hypersensitivity reactions, dizziness, nausea, vomiting, abdominal discomfort or https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IX2deLl%2f4FdfKSHmHSZ7peJYyAcbNSqCsVXJC0jIBoV… 8/23 11/20/23, 5:29 PM Realizeit for Student cramping, malabsorption of amino acids, and diarrhea. Contraindications Contraindications to metformin include diabetes complicated by fever, severe infections, severe trauma, major surgery, acidosis, or pregnancy (insulin is indicated in these conditions). Patients with serious hepatic or renal impairment, cardiac or respiratory insufficiency, hypoxia, or a history of lactic acidosis should not take the drug because these conditions may increase production of lactate and the risk of potentially fatal lactic acidosis (see note above about BLACK BOX WARNING ♦). Nursing Implications Preventing Interactions Some drugs increase the effects of metformin. Use with sulfonylureas, furosemide, cationic drugs such as digoxin, and vancomycin increases the risk of hypoglycemia. Administering the Medication The nurse should ensure that renal function is assessed before starting metformin and at least annually during long-term therapy. Patients should take metformin with meals. They should swallow the extended-release formulation whole and take it with the evening meal. They should discontinue the drug immediately if they are diagnosed with a myocardial infarction. Assessing for Therapeutic Effects The nurse assesses fasting, preprandial, and postprandial blood glucose for normal or near-normal levels. Also, the nurse assesses for improvement in hemoglobin A1C levels. Assessing for Adverse Effects The nurse assesses the skin for eczema, pruritus, erythema, and urticaria. All of these symptoms are indicative of a hypersensitivity reaction. It is also necessary to assess the GI response to the medication. In addition, the nurse assesses for abdominal pain, nausea, vomiting, and diarrhea. It is essential to check the liver function to determine the onset of lactic acidosis. Blood lactate levels are above 5 mmol/L, and blood pH is below 7.35. Symptoms and signs of lactic acidosis may include drowsiness, malaise, respiratory distress, bradycardia, and hypotension. https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IX2deLl%2f4FdfKSHmHSZ7peJYyAcbNSqCsVXJC0jIBoV… 9/23 11/20/23, 5:29 PM Realizeit for Student Thiazolidinediones Thiazolidinediones are sometimes called “glitazones” and are also referred to as insulin sensitizers. These drugs decrease insulin resistance, a major factor in the pathophysiology of type 2 diabetes. Rosiglitazone maleate (Avandia) is the prototype for the thiazolidinediones. Pharmacokinetics Rosiglitazone has a delayed onset of action and takes up to 12 weeks to reach its maximum effects. It is 99.8% protein bound primarily by albumin. The medication is metabolized in the liver by cytochrome P450 (CYP) 2C8, and a minor portion is metabolized by CYP2C9. The serum half-life is 3 to 4 hours. The peak plasma level is reached in 1 hour, with delayed absorption when taken with food. Sixty-four percent of the medication is excreted in the urine and 23% in the feces. Action Rosiglitazone stimulates receptors on muscle, fat, and liver cells, thus increasing or restoring the effectiveness of circulating insulin. This change results in increased uptake of glucose by peripheral tissues and decreased production of glucose by the liver. In addition, this drug decreases insulin resistance, a major factor in the pathophysiology of type 2 diabetes. Use Patients may take rosiglitazone as monotherapy with diet and exercise or in combination with insulin, metformin, a sulfonylurea, an amylin analog (pramlintide), or glucagon-like peptide-1 receptor agonist (exenatide). Use in Patients With Hepatic Impairment Rosiglitazone has been associated with hepatotoxicity and requires monitoring of liver enzymes. Liver function tests (e.g., serum aminotransferase enzymes) should be checked before starting therapy and periodically thereafter. After initiation of thiazolidinedione therapy, it is important to measure liver enzymes every 2 months for 1 year and then periodically. Adverse Effects GI adverse effects of thiazolidinedione include liver injury and diarrhea. The most common respiratory adverse effects are sinusitis, upper respiratory infection, rhinitis, https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IX2deLl%2f4FdfKSHmHSZ7peJYyAcbNSqCsVXJC0jIBo… 10/23 11/20/23, 5:29 PM Realizeit for Student and dyspnea. Congestive heart failure and myocardial infarction are the most severe adverse effects. Contraindications Contraindications to rosiglitazone use include active liver disease or a serum alanine aminotransferase value more than 2.5 times the upper limit of normal, as well as hypersensitivity to the drug. Caution is necessary when patients are at risk for congestive heart failure. Authorities do not recommend rosiglitazone for patients who have symptomatic congestive heart failure. Rosiglitazone increases plasma volume and may cause fluid retention. In one study, heart failure developed in 4.5% of rosiglitazone users within 10 months and in 12.4% of users within 36 months. In people who did not take a thiazolidinedione, 2.6% developed heart failure within 10 months and 8.4% within 36 months. The FDA has issued a BLACK BOX WARNING alerting health care professionals about the risk of congestive heart failure in patients using pioglitazone and rosiglitazone. Assess the patient for excessive weight gain, dyspnea, and edema. A meta-analysis of several studies and clinical trials have raised concerns about increased risk of myocardial ischemic events, including angina, myocardial infarction (heart attack), and heart-related deaths, with rosiglitazone. It is not recommended for patients with symptomatic heart failure. Nursing Implications Preventing Interactions Rosiglitazone serum levels may increase if the antidiabetic drug is taken with gemfibrozil, so it is essential to monitor the patient closely and make dosage adjustments if necessary. Administering the Medication It is important to take rosiglitazone with meals. A patient may take a missed dose at the next meal. (However, if the patient skips a dose for an entire day, he or she should not take a double dose.) Assessing for Therapeutic Effects The nurse assesses fasting, preprandial, and postprandial blood glucose for normal or near-normal levels. Also, the nurse assesses for improvement in hemoglobin A1C levels. Assessing for Adverse Effects https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IX2deLl%2f4FdfKSHmHSZ7peJYyAcbNSqCsVXJC0jIBo… 11/23 11/20/23, 5:29 PM Realizeit for Student The nurse assesses the patient’s cardiopulmonary status by auscultating the lungs for crackles or gurgles and auscultating the heart for an audible S3 that indicates heart failure. Also, it is necessary to assess for signs of hepatic insufficiency and check liver enzymes. In addition, it is essential to assess for upper respiratory congestion. Patient Teaching The nurse teaches patients to report any signs or symptoms of congestive heart failure (e.g., dyspnea, fatigue, peripheral edema) to appropriate health care personnel. Meglitinides Meglitinides are nonsulfonylureas that lower blood sugar by stimulating pancreatic secretion of insulin. Repaglinide (Prandin) is the prototype meglitinide drug. The ability of repaglinide to work effectively depends on the existence of functioning beta cells left in the pancreas. Administration in combination with metformin or insulin results in a greater reduction in a patient’s hemoglobin A1C than when either medication is administered alone. Pharmacokinetics Absorption of repaglinide from the GI tract is good, and peak plasma level occurs within 1 hour. The drug has a plasma half-life of 1 to 1.5 hours and is highly bound (greater than 98%) to plasma proteins. Metabolism occurs in the liver. Excretion of metabolites is in urine and feces. Metabolism and removal of repaglinide from the bloodstream occurs within 3 to 4 hours after a dose. This decreases the workload of pancreatic beta cells (i.e., decreases duration of beta-cell stimulation), allows serum insulin levels to return to normal before the next meal, and decreases risks of hypoglycemic episodes. Action Repaglinide works by closing potassium channels in pancreatic beta cells, which causes calcium channels to open and release insulin. The ability to lower blood glucose is dependent on the amount of functioning beta cells in the pancreas. Use https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IX2deLl%2f4FdfKSHmHSZ7peJYyAcbNSqCsVXJC0jIBo… 12/23 11/20/23, 5:29 PM Realizeit for Student Repaglinide can be used as monotherapy with diet and exercise or in combination with metformin or thiazolidinediones. Dosage is flexible, depending on food intake, but patients should eat within a few minutes after taking a dose to avoid hypoglycemia. Use in Patients With Renal Impairment Assessment of renal function should occur before initiation of treatment with repaglinide and periodically during therapy. The drug requires a decrease in initial dosage in patients with renal disease as well as for those with moderate to severe renal dysfunction. It is necessary to make incremental dosage changes cautiously in patients with renal impairment or renal failure requiring hemodialysis. Use in Patients With Hepatic Impairment Cautious use of repaglinide is warranted in patients with moderate to severe hepatic impairment. It is necessary to make incremental dosage changes very slowly because serum drug levels are higher for a long period. Adverse Effects Hypoglycemia is the most common adverse effect of repaglinide. Other adverse effects are upper respiratory congestion and gastric upset. Contraindications Repaglinide is contraindicated in patients with hypersensitivity. It is also contraindicated in patients with Type 1 diabetes or patients with DKA. Nursing Implications Preventing Interactions The risk of severe hypoglycemia is associated with the use of repaglinide with gemfibrozil and itraconazole. Therefore, such drug combinations should be avoided. Administering the Medication Patients should take repaglinide just before or up to 30 minutes before meals. If a meal is skipped, the drug dose should be skipped; if a meal is added, a drug dose should be added. Assessing for Adverse and Therapeutic Effects The nurse assesses fasting, preprandial, and postprandial blood glucose for normal or near-normal levels. It is also important to assess for improvement in hemoglobin A1C levels. https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IX2deLl%2f4FdfKSHmHSZ7peJYyAcbNSqCsVXJC0jIBo… 13/23 11/20/23, 5:29 PM Realizeit for Student The nurse assesses for dizziness, weakness, and hunger. In addition, he or she assesses for gastric upset and respiratory congestion. Patient Teaching When instructing patients who have been prescribed meglitinides, it is necessary to inform them that if they skip a meal, then they should also skip the dose. If they add a meal, then they need to take a dose before the meal. The nurse teaches patients taking repaglinide to know and recognize the signs and symptoms of hypoglycemia and how to treat the condition immediately. Dipeptidyl Peptidase 4 Inhibitors GLP-1 has been known for some time to have a hypoglycemic action via its ability to stimulate insulin secretion. Recent advances have overcome the problems associated with short half-life and inactivation of the incretin hormone. The DPP-4 enzyme inhibitor sitagliptin (Januvia) is a new medication that solves these problems. Pharmacokinetics Sitagliptin is rapidly absorbed and distributed with 3% protein bound. The drug is metabolized minimally by CYP3A4 and CYP2C8, resulting in a 12-hour circulating halflife for GLP-1. The peak of action is 1 to 4 hours. Eighty-seven percent of the medication is excreted in the urine with 79% unchanged. Approximately 13% is excreted in the feces. Action Sitagliptin minimizes the rate of inactivation of the incretin hormones to increase hormone levels and prolong their activity. Incretin hormones stimulate insulin release in response to a meal to normalize glucose levels. This action increases and lengthens the release of insulin and decreases hepatic glucose production to promote glycemic control. Use https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IX2deLl%2f4FdfKSHmHSZ7peJYyAcbNSqCsVXJC0jIBo… 14/23 11/20/23, 5:29 PM Realizeit for Student Patients with type 2 diabetes mellitus take sitagliptin in addition to following an exercise and diet regimen. They may also take it in combination with metformin and/or thiazolidinediones. Use in Patients With Renal Impairment Caution is warranted in renal insufficiency because sitagliptin is excreted by the kidneys. Patients with an elevated creatinine clearance require decreased dosages initially. Dosage adjustments are also necessary in the earlier stages of chronic kidney diseases. Adverse Effects Common adverse effects of sitagliptin are upper respiratory tract infection, stuffy or runny nose, sore throat, and headache. Contraindications Contraindications to sitagliptin use include type 1 diabetes mellitus, insulin use, or the common production of ketones in the urine. Another contraindication is end-stage renal disease. Strict avoidance of other medications known to cause hypoglycemia, such as sulfonylureas, is warranted. The FDA has identified a risk of heart failure associated with DPP-4 inhibitors. This risk is more pronounced in patients with kidney and heart disease. Nursing Implications Administering the Medication Patients should take sitagliptin once daily with or without food. If they forget to take a dose, they should take it as soon as possible. However, if a dose is skipped, patients should take only one dose per day. Assessing for Therapeutic and Adverse Effects The nurse assesses fasting, preprandial, and postprandial blood glucose for normal or near-normal levels. It is also important to assess for improvement in hemoglobin A1C levels. In addition, the nurse assesses the patient for signs and symptoms of upper respiratory infection. https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IX2deLl%2f4FdfKSHmHSZ7peJYyAcbNSqCsVXJC0jIBo… 15/23 11/20/23, 5:29 PM Realizeit for Student Amylin Analogs Some people with type 1 or type 2 diabetes cannot achieve optimal glucose control with insulin therapy alone. Pramlintide acetate (SymlinPen 120, SymlinPen 60) is a newer drug used as an adjunctive treatment with mealtime insulin that is important in the regulation of glucose control during the postprandial period. A synthetic analog of amylin, pramlintide is a peptide hormone secreted with insulin by the beta cells of the pancreas. Pharmacokinetics Pramlintide has a rapid onset of action, reaching its peak in 20 minutes, with a 3-hour duration of action. Sixty percent of the drug is protein bound. It is metabolized primarily in the renal system and excreted in the urine. Action Pramlintide slows gastric emptying, which helps regulate the postprandial rise in blood glucose. The drug also suppresses postprandial glucagon secretion, thus helping maintain better blood glucose control. It also increases the sense of satiety, possibly reducing food intake and promoting weight loss. Use Taken immediately before meals, pramlintide mimics the body’s natural processes. Oral hypoglycemic drugs and insulin dosages are usually up to 50% lower as well, depending on the patient’s response to the drug. Patients with type 2 disease may combine pramlintide and insulin therapy with metformin or sulfonylureas. Adverse Effects Nausea, another frequent adverse effect of pramlintide, tends to decrease with time. Careful titration of the dosage to the therapeutic level may reduce it. A BLACK BOX WARNING ♦ alerts nurses to the danger of severe insulin-induced hypoglycemia with pramlintide therapy, especially in Type 1 diabetes. Contraindications The only contraindications to pramlintide are hypersensitivity and gastroparesis. Nursing Implications Preventing Interactions https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IX2deLl%2f4FdfKSHmHSZ7peJYyAcbNSqCsVXJC0jIBo… 16/23 11/20/23, 5:29 PM Realizeit for Student Some drugs may increase the effects of pramlintide. Pramlintide also can cause increased effects of gastric emptying if combined with anticholinergic drugs or drugs that slow gastric absorption of nutrients. It is essential to avoid pramlintide with such drugs. Administering the Medication Subcutaneous injection of pramlintide before meals is necessary. The patient should not use pramlintide if a meal is skipped or if a dose is forgotten. It is necessary to inject pramlintide into a site (thigh or abdomen) that is at least 2 inches away from the insulin site injection. Opened vials of pramlintide may be stored in a refrigerator or at room temperature for up to 28 days. It is essential not to mix pramlintide in the same injection with mealtime insulin. Patients with type 2 diabetes should take oral hypoglycemic drugs at least 1 hour before or 2 hours after injecting pramlintide. Assessing for Therapeutic and Adverse Effects The nurse assesses fasting, preprandial, and postprandial blood glucose for normal or near-normal levels. It is also important to assess for improvement in the hemoglobin A1C levels. In addition, the nurse teaches the signs and symptoms of hypoglycemia, as well as its treatment. This is the only serious adverse effect. GLUCAGON-LIKE PEPTIDE-1 RECEPTOR AGONISTS (INCRETIN MIMETICS) Before starting a patient with type 2 diabetes on insulin, the provider should consider a new option for treatment of diabetes. The glucagon-like peptide-1 receptor agonist is also known as the incretin mimetic exenatide (Bydureon, Byetta 10 MCG Pen, Byetta 5 MCG PEN), a synthetic GLP-1 analog; it is possible to improve glycemic control in patients with type 2 diabetes who are already taking an oral hypoglycemic medication but having difficulty in achieving glycemic control. Pharmacokinetics https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IX2deLl%2f4FdfKSHmHSZ7peJYyAcbNSqCsVXJC0jIBo… 17/23 11/20/23, 5:29 PM Realizeit for Student Exenatide has a rapid onset, and the peak effect occurs in 2 hours. The drug is metabolized minimally and has proteolytic degradation following glomerular filtration. It remains in the body for 8 to 10 hours, which means that dosages must be 6 hours apart. It has a 2.4-hour half-life and is excreted in the urine. Exenatide also crosses the placenta; thus, this drug must be used cautiously in patients who are pregnant. Action Exenatide acts as a natural helper hormone by stimulating the pancreas to secrete the right amount of insulin based on the food that was just eaten. This helps reduce the problem of high blood glucose after meals. The drug also halts gluconeogenesis by the liver, keeping it from making too much glucose after a meal. Exenatide slows gastric emptying, which serves to reduce the sudden rise of blood glucose after a meal, and it also quickly stimulates a feeling of satiety when eating. This fosters a sense of fullness, which causes the patient to eat less and potentially lose weight. Use When oral medications, diet, and exercise together have not assisted in reaching the target hemoglobin A1C goal, prescribers may now order exenatide. The FDA has approved its use with oral medications such as sulfonylureas, metformin, and/or thiazolidinediones. Major advantages of exenatide over insulin are increased satiety and weight loss. Exenatide is also now being used as monotherapy in combination with diet and exercise for newly diagnosed adults with type 2 diabetes. Adverse Effects Major adverse effects of exenatide are hypoglycemia, GI distress, and nausea. Many patients experience nausea at first, and health care providers should encourage them to continue the medication if at all possible because the nausea usually subsides and becomes a feeling of fullness. A rare but serious side effect is the development of acute pancreatitis. Contraindications Contraindications to exenatide include a known hypersensitivity to the drug. Patients with liver disease or elevated liver enzymes should not receive it with HMG-CoA reductase inhibitors. Lactation is also a contraindication. The FDA has issued a BLACK BOX WARNING for exenatide; C-cell thyroid cancer has developed in studies of animals who were given the drug. Patients should routinely be https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IX2deLl%2f4FdfKSHmHSZ7peJYyAcbNSqCsVXJC0jIBo… 18/23 11/20/23, 5:29 PM Realizeit for Student monitored for thyroid nodules, and the drug is contraindicated in patients with a family history of endocrine neoplasia syndrome type 2. Nursing Implications Preventing Interactions Like pramlintide, exenatide may reduce the absorption of concurrently administered oral medications due to slow gastric emptying. Administering the Medication Patients administer exenatide subcutaneously twice a day within 60 minutes of the morning and evening meal (at least 6 or more hours apart). No dosage adjustment is necessary based on blood glucose levels or the amount of food a patient is able to consume. If patients forget a dose, they should not inject exenatide after a meal. Injection sites include the subcutaneous tissue of the upper arm or leg and the abdomen areas. It is essential that exenatide be stored at all times in the original packaging in a refrigerator at 36°F to 46°F, protected from light, kept dry, and discarded once opened after 30 days. Assessing for Therapeutic Effects The nurse assesses fasting, preprandial, and postprandial blood glucose for normal or near-normal levels. It is also important to assess for improvement in hemoglobin A1C levels. Assessing for Adverse Effects It is important that patients and their caregivers recognize the signs and symptoms of hypoglycemia, a possible adverse effect of exenatide, and be prepared to treat hypoglycemia with fast-acting sugar or glucagon. If patients are unable to eat or plan to skip a meal, they should not take the drug. Patients taking exenatide should report any unusual abdominal discomfort to their health care providers because acute pancreatitis is a possible adverse effect of the medication. Sodium Glucose Cotransporter 2 (SGLT2) Inhibitors In 2013, the FDA approved the first SGLT2 inhibitor. The prototype of this class is canagliflozin (Invokana). The drug inhibits renal SGLT2, thus blocking reabsorption of glucose in the kidney. In addition, it promotes the excretion of excess glucose in the https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IX2deLl%2f4FdfKSHmHSZ7peJYyAcbNSqCsVXJC0jIBo… 19/23 11/20/23, 5:29 PM Realizeit for Student urine. All the SGLT2 inhibitors provide renal protection by decreasing the protein loss and reducing the damage caused by hyperfiltration. Pharmacokinetics Canagliflozin is 99% bound to albumin. The peak of action is 1 to 2 hours. For a 100-mg dose, the half-life of the drug is 10.6 hours, and for a 300-mg dose, it is 13.1 hours. The drug is metabolized by glucuronidation. The elimination of the drug is 30% in the urine and 52% in the feces. Action The proximal renal tubule is the site where the majority of filtered glucose is reabsorbed, and in this tubule, canagliflozin inhibits SGLT2. This action provides the patient with Type 2 diabetes greater excretion of glucose by the kidney. Use Prescribers order canagliflozin in combination with other antidiabetic agents to promote improvement in glycemic control in patients with Type 2 diabetes. Use in Patients With Hepatic Impairment Patients with severe hepatic impairment should not take canagliflozin. Use in Patients With Renal Impairment In patients with an estimated glomerular filtration rate of 45 to 59 mL/min, the dosage of canagliflozin should not exceed 100 mg daily. It is not recommended that patients with an estimated glomerular filtration rate less than 45 mL/min take canagliflozin. Adverse Effects The loss of body fluids leads to dehydration, hypotension, syncope, and dehydration. The metabolic adverse effects include increased low-density lipoprotein, hyperphosphatemia, hyperkalemia, hypermagnesemia, and increased creatinine. Because of increases in urine glucose, patients are prone to genital mycotic infections. Approximately 12% of women develop vulvovaginal candidiasis. Four percent of men develop inflammation of the glans penis; this includes balanitis/balanoposthitis, balanitis candida, and fungal genital infection. The administration of potassium-sparing diuretics with SGLT2 inhibitors causes hyperkalemia. In addition, in June 2016, the FDA identified the risk of acute kidney injury with canagliflozin. Health Canada found evidence of a link between bone-related adverse https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IX2deLl%2f4FdfKSHmHSZ7peJYyAcbNSqCsVXJC0jIBo… 20/23 11/20/23, 5:29 PM Realizeit for Student effects, including demineralization of the bone and risk of bone fractures. In May 2017, an FDA alert was issued. Canagliflozin causes an increased risk of leg and foot amputations. Contraindications Severe renal impairment and hypersensitivity reactions contraindicate the administration of canagliflozin. Nursing Implications Preventing Interactions SGLT2 inhibitors combined with angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs), and loop diuretics that have hypotensive effects will lead to symptoms of syncope, hypotension, and hyperkalemia. In addition, hyperkalemia will result with potassium-sparing diuretics. St. John’s wort will decrease the serum concentration of the SGLT2 inhibitors, leading to hyperglycemia. Administering the Drug Prior to administering SGLT2 inhibitors, patients should be well hydrated. The initial dose should be low. Patients should take the drugs with the first meal of the day. Assessing for Therapeutic Effects The nurse assesses fasting, preprandial, and postprandial blood glucose for normal or near-normal levels. It is also important to assess for improvement in hemoglobin A1C levels. Assessing for Adverse Effects It is imperative to assess the patient’s hydration level and blood pressure for signs and symptoms of syncope and hypotension. The nurse should assess the potassium level and alert the prescriber of hyperkalemia. In the event of hyperkalemia, it is important to check the patient’s cardiac rhythm for dysrhythmia. Adjuvant Medications Used to Treat Diabetes For most patients, the goals of treatment are to maintain blood glucose at normal or near-normal levels; promote normal metabolism of carbohydrate, fat, and protein; prevent acute and long-term complications; and prevent hypoglycemic episodes. There is strong evidence that strict control of blood sugar delays the onset and slows https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IX2deLl%2f4FdfKSHmHSZ7peJYyAcbNSqCsVXJC0jIBo… 21/23 11/20/23, 5:29 PM Realizeit for Student progression of complications of diabetes. In addition to glycemic control, other measures can be used to help prevent complications of diabetes. Angiotensin-Converting Enzyme Inhibitors The prototype ACE inhibitor is enalapril maleate (Vasotec). Enalapril maleate blocks the conversion of angiotensin I to angiotensin II, thereby decreasing blood pressure. Enalapril maleate has protective effects on the kidneys in both type 1 and type 2 diabetes and in both normotensive and hypertensive people. Although ACE inhibitors are also used in the treatment of hypertension, their ability to delay nephropathy seems to be independent of antihypertensive effects. Additional measures to preserve renal function include effective treatment of hypertension, limited intake of dietary protein, prompt treatment of urinary tract infections, and avoidance of nephrotoxic drugs when possible. Serum potassium levels and creatinine levels should be monitored. Angiotensin II Receptor Blockers Losartan (Cozaar) is the prototype ARB. In renal studies of patients with diabetes and nephropathy, losartan reduced the incidence of end-stage renal disease in 28% of the patients. ARBs do not prevent nephropathy but reduce the rate of progression. Serum potassium levels and creatinine levels should be monitored. Thiazide-Like Diuretics Hydrochlorothiazide (HCTZ) is the prototype thiazide-like diuretics. Thiazide-like diuretics have been shown to reduce cardiovascular events in diabetes. Serum potassium levels and creatinine levels should be monitored. Antiplatelet Agent Aspirin therapy is considered a primary prevention strategy in patients with diabetes who are at increased cardiovascular risk. HMG-CoA Reductase Inhibitors The prototype HMG-CoA reductase inhibitor is simvastatin (Zocor). Simvastatin inhibits HMG-CoA reductase, the enzyme that catalyzes the first step in cholesterol synthesis, which ultimately reduces serum cholesterol. Current research suggests that a number of treatment strategies may be beneficial in reducing the cardiovascular disease risk associated with type 2 diabetes mellitus. Some clinicians are recommending the routine https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IX2deLl%2f4FdfKSHmHSZ7peJYyAcbNSqCsVXJC0jIBo… 22/23 11/20/23, 5:29 PM Realizeit for Student use of statins such as simvastatin to reduce the risk of occlusive arterial disease in all patients with diabetes, regardless of cholesterol level. https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IX2deLl%2f4FdfKSHmHSZ7peJYyAcbNSqCsVXJC0jIBo… 23/23