Diabetes Melitus
R.A. is a 52-year-old Type 2 diabetic patient. For the past few months, he has been treated with corticosteroids for severe inflammatory bowel disease (IBD). His recent morning (pre-breakfast) fasting blood glucose levels are normal, but he is experiencing progressively elevated pre-lunch and pre-dinner glucose levels. Which of the following would be the most appropriate drug to treat this patient's hyperglycemia? -Aspart -Detemir -Glargine -Glyburide
Aspart. Aspart is a rapid-acting insulin. This patient has a problem with elevated postprandial-related hyperglycemia, which is a known side effect of treatment with glucocorticoids. He would benefit from a rapidly acting form of insulin given "as part" of his meals. Detemir and glargine are basal insulins. This patient has a problem with elevated prandial-related hyperglycemia, as compared to baseline control of insulin. Sulfonylureas would not be the best choice, because they would not selectively target the lowering of postprandial hyperglycemia.
D.B. is a 58-year-old overweight woman with a history of Type 2 diabetes that has been well controlled with metformin and glyburide (a sulfonylurea) until recently. Her record of glucose readings indicate normal morning (fasting) glucose levels (80-100 mg/dL), but a progressively increasing high glucose level before lunch (>110 mg/dL) and before dinner (190-200 mg/dL). Her lab values are all within normal limits, and she has no history of kidney or heart disease. She has a strong distaste for needles and would prefer sticking to oral medications. Which medication would be appropriate for addressing D.B.'s problem with glucose control? -GLP-1 agonist (Exenatide) -Sulfonylurea (Glimepiride) -DPP-4 inhibitor (Sitagliptin) -Amylin Analog (Pramlintide)
DPP-4 inhibitor (Sitagliptin). DPP-4 inhibitors are taken orally and are approved for use as adjuncts with other anti-diabetic medications, except for insulin. Amylin analog and GLP-1 agonists would be a good option in many patients, but D.B. has a phobia about giving injections. The patient is already taking a sulfonylurea, and adding a second drug with the same mechanism of action (glimepiride) to her drug regimen would likely not be helpful.
N.B. is an obese 52-year old Type 2 diabetic (280 lbs, 5'10"), currently being treated with both glyburide (a sulfonylurea) and metformin. He comes to your office complaining about frequent episodes of hypoglycemia. After discussing the need for lifestyle changes and the different possible therapeutic options, you decide to replace his glyburide with an agent that is less likely to produce hypoglycemia, and more likely to produce weight loss. Which of the following agents will you choose? -GLP-1 agonist (Exenatide) -Sulfonylurea (Glipizide) -Thiazolidinedione (Rosiglitazone) -DPP-4 inhibitor (Sitagliptin)
GLP-1 agonist (Exenatide). The GLP-1 mimetics have a record of producing a steady weight loss due primarily to their central effects. They are unlikely to produce significant hypoglycemia, unless combined with a sulfonylurea. Glipizide is another sulfonylurea (like glyburide). Thiazolidinediones increase weight gain. While the DPP-4 inhibitors do not produce hypoglycemia, they have not been found to produce weight loss. This is most likely due to their modest effect to increase endogenous GLP-1 levels.
D.W. is a patient with Type 2 diabetes who has a blood glucose of 400 mg/dL today at his office visit. The physician would like to give some insulin to bring the glucose down before he leaves the office. Which of the following would lower his glucose in the quickest manner? -Insulin Aspart -Insulin glargine -NPH insulin -Regular insulin
Insulin aspart. Insulin aspart is a rapid-acting insulin that has an onset of action within 15-20 minutes. Insulin glargine is a long0acting insulin that is used for basal control. NPH insulin is an intermediate-acting insulin that is used for basal control. Although regular insulin can be used to bring the glucose down, its onset is not as quick as insulin aspart. The onset of regular insulin is about 30-60 minutes.
Which of the following statements is correct regarding insulin glargine? -It is primarily used to control postprandial hyperglycemia -It is a "peakless" insulin -The prolonged duration of activity is due to slow dissociation from albumin -It should not be used in regimen with insulin lispro or glulisine -It may be administered intravenously in emergency cases
It is a "peakless" insulin. Insulin glargine has a relatively flat, prolonged hypoglycemic effect. Because of this, it is used for basal glucose control, not postprandial. The prolonged duration is due to its low pH, which leads to precipitation at the injection site and resultant extended action. Insulin glargine is often used for basal control in a regimen where insulin lispro, glulisine, or aspart are used for mealtime glucose control. [Note: Glargine should not be combined with other insulins in the same syringe, as it may alter the pharmacodynamic properties of the medication.]
Which of the following diabetes medications is most appropriately paired with an adverse effect associated with its use? -Canagliflozin - lactic acidosis -Metformin - urinary tract infections -Nateglinide - heart failure -Liraglutide - pancreatitis
Liraglutide - pancreatitis. The incretin mimetics are associated with a risk of pancreatitis. Lactic acidosis is a rare but serious side effect of metformin (not canagliflozin). Adverse effects of canagliflozin are genital mycotic infections, urinary tract infections, and urinary frequency. Nateglinide may cause hypoglycemia, but has not been associated with heart failure. TZDs have been associated with heart failure.
Which of the following drugs for diabetes would be LEAST likely to cause weight gain? -Glimerpiride -Liraglutide -Pioglitazone -Repaglinide -Insulin glulisine
Liraglutide. Incretin mimetics are usually associated with weight loss due to their ability to enhance satiety. All of the other agents are associated with weight gain.
Which of the following is a type of "prandial" insulin secretagogue that needs to be taken orally before each meal, and has a relatively low risk for producing unwanted hypoglycemia? -Sulfonylurea (Glyburide) -GLP-1 analog (Liraglutide) -Biguanide (Metformin) -Thiazolidinedione (Pioglitazone) -Meglitinide (Repaglinide)
Meglitinide (Repaglinide). Meglitinides produce less hypoglycemia compared to sulfonylureas but have to be taken before each meal. TZDs are insulin sensitizers and not a secretagogue. GLP-1 mimetics need to be injected subcutaneously twice a day. Sulfonylureas are secretagogues that are given once a day and have the largest effect on fasting glucose levels versus postprandial glucose levels. They are known for producing hypoglycemia as an unwanted side effect as an extension of their action.
Which of the following statements is characteristic of metformin? -Metformin is inappropriate for the initial management of Type 2 diabetes -Metformin decreases hepatic glucose production -Metformin undergoes significant metabolism via the cytochrome P450 system -Metformin should not be combined with sulfonylureas or insulin -Weight gain is a common adverse effect
Metformin decreases hepatic glucose production. Metformin works by inhibiting hepatic gluconeogenesis. It is the preferred initial agent for the management of Type 2 diabetes. Metformin is not metabolized. It may be combined with sulfonylureas, insulin, or TZDs. Unlike sulfonylureas and insulin, weight gain is not an adverse effect, and some patients actually lose weight due to GI side effects.
Which of the following is the most appropriate initial oral agent for the management of Type 2 diabetes in patients with no other comorbid conditions? -Glipizde -Insulin -Metformin -Pioglitazone
Metformin. Metformin is the preferred initial agent for management of Type 2 diabetes.
K.D. is a 69-year-old male with Type 2 diabetes and advanced chronic kidney disease. Which of the following diabetes medications is contraindicated in this patient? -Glipizide -Insulin Lispro -Metformin -Saxagliptin
Metformin. Metformin should not be used with kidney disease due to the possibility of lactic acidosis. Glipizide can be used safely in patients with CrCl as low as 10 mL/min. Insulin is not contraindicated in renal dysfunction, although the dosage may need to be adjusted. While the dose of the DPP-4 inhibitor saxagliptin may need to be reduced in renal dysfunction, it is not contraindicated.
A 64-year-old woman with a history of Type 2 diabetes is diagnosed with heart failure. Which of the following medication would be a poor choice for controlling her diabetes? -Exenatide -Glyburide -Nateglinide -Pioglitazone -Sitagliptin
Pioglitazone. The TZDs (pioglitazone and rosiglitazone) can cause fluid retention and lead to a worsening of heart failure. They should be used with caution and dose reduction, if at all, in patients with heart failure. Exenatide, glyburide, nateglinide, and sitagliptin do not have precautions for use in heart failure patients.
A patient with Type 2 diabetes is taking metformin. The fasting glucose levels are in range, but the postprandial glucose is uncontrolled. All of the following drugs would be appropriate to add to metformin to target postprandial glucose except? -Acarbose -Exenatide -Insulin Aspart -Pramlintide
Pramlintide. Although all of these drugs target postprandial glucose, pramlintide should only be used in conjunction with mealtime insulin. Since this patient is not on insulin, pramlintide is not indicated.
Which of the following produces CNS-mediated effects to decrease hunger and delay gastric emptying, suppresses the release of glucagon, and can be used along with insulin in BOTH Type1 and Type 2 diabetic patients? -Exenatide -Nateglinide -Pramlintide -Sitagliptan -Glipizide
Pramlintide. Pramlintide is a soluble analog of amylin, the peptide that is co-released with insulin by pancreatic beta cells. It can be used in both Type 1 and Type 2 diabetics. Exenatide (Byetta) and DPP-4 inhibitors (Saxagliptin) work to stimulate insulin release, and this requires the existence of functional pancreatic beta cells. Type 1 diabetics lack functional beta-cells. Acarbose doesn't have CNS-mediated effects, affect gastric emptying, or affect glucagon release.
J.T. is a 24-year-old man (280 lb. and 5'8") who is brought into the Emergency Department by his parents. J.T. has been feeling nauseated, shaky, and feverous the past few hours. Upon examination, J.T. appears to be sweating abnormally and has difficulty speaking and concentrating during the conversation. While taking his history, J.T. admits to having recently changed his diabetic medications. Which of the following would be the most likely cause of J.T.'s recent onset of symptoms? -Alpha-glucosidase inhibitor (Acarabose) -Sulfonylurea (Glyburide) -Biguanide (Metformin) -Thiazolidinedione (Pioglitazone) -DPP-4 Inhibitor (Sitagliptin)
Sulfonylurea (Glyburide). Sulfonylureas are known for producing hypoglycemia, the symptoms that J.T. is suffering from due to overmedication relative to his level of carbohydrate consumption. Metformin, pioglitazone, and sitagliptin are all "euglycemic" medications and are unlikely to contribute to J.T.'s hypoglycemic symptoms.
Which of the following classes of oral diabetes drugs is paired most appropriately with its primary mechanism of action? -DPP-4 inhibitor; inhibits the breakdown of complex carbohydrates -Glinide; increases insulin sensitivity -Sulfonylurea; increases insulin secretion -Thiazolidinedione; decreases hepatic gluconeogenesis
Sulfonylurea; increases insulin secretion. Sulfonylureas work primarily by increasing insulin secretion through stimulation of the β cells of the pancreas. DPP-4 inhibitors work by inhibiting the breakdown of incretins, thereby increasing postprandial insulin secretion, decreasing postprandial glucagon, etc. Glinides work primarily by increasing insulin secretion. TZDs work primarily by increasing insulin sensitivity.