Chapter 32
Antidiabetic Drugs
Copyright © 2014 by Mosby, an imprint of Elsevier Inc.
Diabetes Mellitus


Diabetes mellitus (DM) actually is not a single
disease, but a group of progressive diseases. It
is often regarded as a syndrome rather than a
disease.
Two types


Type 1
Type 2
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Diabetes Mellitus (cont’d)

Signs and symptoms

Elevated fasting blood glucose (higher than 126
mg/dL) or a hemoglobin A1C (A1C) level greater than
or equal to 6.5%
 Polyuria
 Polydipsia
 Polyphagia
 Glycosuria
 Unexplained weight loss
 Fatigue
 Blurred vision
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Type 1 Diabetes Mellitus




Lack of insulin production or production of
defective insulin
Affected patients need exogenous insulin
Fewer than 10% of all diabetes cases are type 1
Complications


Diabetic ketoacidosis (DKA)
Hyperosmolar nonketotic syndrome
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Type 2 Diabetes Mellitus



Most common type: 90% of all cases
Caused by insulin deficiency and insulin
resistance
Many tissues are resistant to insulin


Reduced number of insulin receptors
Insulin receptors less responsive
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Type 2 Diabetes Mellitus (cont’d)

Several comorbid conditions

Obesity
 Coronary heart disease
 Dyslipidemia
 Hypertension
 Microalbuminemia (protein in the urine)
 Increased risk for thrombotic (blood clotting) events

These comorbidities are collectively referred to
as metabolic syndrome or insulin-resistance
syndrome or syndrome X
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Gestational Diabetes




Hyperglycemia that develops during pregnancy
Insulin must be given to prevent birth defects
Usually subsides after delivery
30% of patients may develop Type 2 DM within
10 to 15 years
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Classroom Response Question
A woman who has type II diabetes is now pregnant. She
wants to know whether to take her oral antidiabetic
medication. What instructions will she receive?
A. She should continue the antidiabetic medication at
the same dosage.
B. The antidiabetic medication dosage will be
increased gradually throughout her pregnancy.
C. She will be switched to insulin therapy while she is
pregnant.
D. She will not receive any antidiabetic medication
while pregnant and will need to monitor her dietary
intake closely.
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Major Long-Term Complications of
DM (Both Types)

Macrovascular (atherosclerotic plaque)




Coronary arteries
Cerebral arteries
Peripheral vessels
Microvascular (capillary damage)



Retinopathy
Neuropathy
Nephropathy
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Screening for DM

Prediabetes

Categories of increased risk for diabetes
• Hemoglobin A1C of 5.7% to 6.4%
• Fasting plasma glucose (FPG) levels higher than or equal to
100 mg/dL but less than 126 mg/dL
• Impaired glucose tolerance test (oral glucose challenge)

Screening recommended every 3 years for all
patients 45 years and older
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Treatment for DM

Type 1


Insulin therapy
Type 2

Lifestyle changes
 Oral drug therapy
 Insulin when the above no longer provide glycemic
control
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Types of Antidiabetic Drugs


Insulins
Oral hypoglycemic drugs


Both aim to produce normal blood glucose states
Some new injectable hypoglycemic drugs may
be used in addition to insulin or antidiabetic
drugs
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Insulins



Function as a substitute for the endogenous
hormone
Effects are the same as normal endogenous
insulin
Restores the diabetic patient’s ability to:



Metabolize carbohydrates, fats, and proteins
Store glucose in the liver
Convert glycogen to fat stores
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Insulins (cont’d)

Human insulin



Derived using recombinant DNA technologies
Recombinant insulin produced by bacteria and yeast
Goal: tight glucose control

To reduce the incidence of long-term complications
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Insulins (cont’d)

Rapid-acting

Most rapid onset of action (5 to 15 minutes)
 Shorter duration
 Patient must eat a meal after injection
 Insulin lispro (Humalog)
• Similar action to endogenous insulin
 Insulin aspart (NovoLog)
 Insulin glulisine (Apidra)
 May be given subcutaneously or via continuous
subcutaneous infusion pump (but not IV)
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Insulins (cont’d)

Short-acting


Regular insulin (Humulin R)
Onset 30 to 60 minutes
• The only insulin product that can be given by IV bolus, IV
infusion, or even IM
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Insulins (cont’d)

Intermediate-acting

Insulin isophane suspension (also called NPH)
• Cloudy appearance
• Slower in onset and more prolonged in duration than
endogenous insulin
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Insulins (cont’d)

Long-acting

glargine (Lantus), detemir (Levemir)
• Clear, colorless solution
• Usually dosed once daily
• Referred to as basal insulin
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Classroom Response Question
The nurse has just administered the morning dose
of a patient’s lispro (Humalog) insulin. Just after
the injection, the dietary department calls to inform
the patient care unit that breakfast trays will be 45
minutes late. What will the nurse do next?
A.
B.
C.
D.
Inform the patient of the delay.
Check the patient’s blood glucose levels.
Call the dietary department to send a tray immediately.
Give the patient food, such as cereal and skim milk,
and juice.
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Insulins (cont’d)

Fixed combinations

Humulin 70/30
 Humulin 50/50
 Novolin 70/30
 Humalog Mix 75/25
 Humalog 50/50
 NovoLog 70/30
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Insulins (cont’d)

Insulin use in special populations


Pediatrics
Pregnant women
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Sliding-Scale Insulin Dosing




Subcutaneous short-acting or regular insulin
doses adjusted according to blood glucose test
results
Typically used in hospitalized diabetic patients or
those on total parenteral nutrition (TPN) or
enteral tube feedings
Subcutaneous insulin is ordered in an amount
that increases as the blood glucose increases
Disadvantage: delays insulin administration until
hyperglycemia occurs; results in large swings in
glucose control
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Basal-Bolus Insulin Dosing




Preferred method of treatment for hospitalized
diabetic patients
Mimics a healthy pancreas by delivering basal
insulin constantly as a basal and then as needed
as a bolus
Basal insulin is a long-acting insulin (insulin
glargine)
Bolus insulin (insulin lispro or insulin aspart)
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Oral Antidiabetic Drugs


Used for type 2 diabetes
Treatment for type 2 diabetes includes lifestyle
modifications


Diet, exercise, smoking cessation, weight loss
Oral antidiabetic drugs may not be effective
unless the patient also makes behavioral or
lifestyle changes
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Oral Antidiabetic Drugs (cont’d)

Biguanides


metformin (Glucophage)
Sulfonylureas

Second generation: glimepiride (Amaryl), glipizide
(Glucotrol), glyburide (DiaBeta, Micronase)
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Oral Antidiabetic Drugs (cont’d)

Glinides


repaglinide (Prandin), nateglinide (Starlix)
Thiazolidinediones

pioglitazone (Actos)
 rosiglitazone (Avandia)
• Only available through specialized manufacturer programs
 Also known as glitazones

Alpha-glucosidase inhibitors

acarbose (Precose), miglitol (Glyset)
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Oral Antidiabetic Drugs (cont’d)

Dipeptidyl peptidase-IV (DPP-IV) inhibitors



sitagliptin (Januvia)
saxagliptin (Onglyza)
linagliptin (Tradjenta)
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Oral Antidiabetic Drugs:
Mechanism of Action

Biguanides

Decrease production of glucose by the liver
 Decrease intestinal absorption of glucose
 Increase uptake of glucose by tissues
 Do not increase insulin secretion from the pancreas
(does not cause hypoglycemia)
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Oral Antidiabetic Drugs:
Mechanism of Action (cont’d)

Sulfonylureas

Stimulate insulin secretion from the beta cells of the
pancreas, thus increasing insulin levels
 Beta cell function must be present
 Improve sensitivity to insulin in tissues
 Result in lower blood glucose levels
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Oral Antidiabetic Drugs:
Mechanism of Action (cont’d)

Glinides


Action similar to sulfonylureas
Increase insulin secretion from the pancreas
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Oral Antidiabetic Drugs:
Mechanism of Action (cont’d)

Thiazolidinediones

Decrease insulin resistance
 “Insulin sensitizing drugs”
 Increase glucose uptake and use in skeletal muscle
 Inhibit glucose and triglyceride production in the liver
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Oral Antidiabetic Drugs:
Mechanism of Action (cont’d)

Alpha-glucosidase inhibitors

Reversibly inhibit the enzyme alpha-glucosidase in
the small intestine
 Result in delayed absorption of glucose
 Must be taken with meals to prevent excessive
postprandial blood glucose elevations (with the “first
bite” of a meal)
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Oral Antidiabetic Drugs:
Mechanism of Action (cont’d)

Dipeptidyl peptidase-IV (DPP-IV) inhibitors



Delay breakdown of incretin hormones by inhibiting
the enzyme DPP-IV
Incretin hormones increase insulin synthesis and
lower glucagon secretion
Reduce fasting and postprandial glucose
concentrations
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Oral Antidiabetic Drugs:
Indications

Used alone or in combination with other drugs
and/or diet and lifestyle changes to lower the
blood glucose levels in patients with type 2
diabetes
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Oral Antidiabetic Drugs:
Adverse Effects

Biguanides (metformin)




Primarily affects GI tract: abdominal bloating, nausea,
cramping, diarrhea, feeling of fullness
May also cause metallic taste, reduced vitamin B12
levels
Lactic acidosis is rare but lethal if it occurs
Does not cause hypoglycemia
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Oral Antidiabetic Drugs:
Adverse Effects (cont’d)

Sulfonylureas


Hypoglycemia, hematologic effects, nausea,
epigastric fullness, heartburn, many others
Glinides

Headache, hypoglycemic effects, dizziness, weight
gain, joint pain, upper respiratory infection or flulike
symptoms
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Oral Antidiabetic Drugs:
Adverse Effects (cont’d)

Thiazolidinediones



Moderate weight gain, edema, mild anemia
Hepatic toxicity—monitor alanine aminotransferase
(ALT) levels
Alpha-glucosidase inhibitors


Flatulence, diarrhea, abdominal pain
Do not cause hypoglycemia, hyperinsulinemia, or
weight gain
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Oral Antidiabetic Drugs:
Adverse Effects (cont’d)

Dipeptidyl peptidase-IV (DPP-IV) inhibitors


Upper respiratory tract infection, headache, and
diarrhea
Hypoglycemia can occur and is more common if
used in conjunction with a sulfonylurea
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Injectable Antidiabetic Drugs

Amylin agonists


pramlintide (Symlin)
Incretin mimetics

exenatide (Byetta)
 liraglutide (Victoza)
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Injectable Antidiabetic Drugs:
Mechanism of Action (cont’d)

Amylin agonist

Mimics the natural hormone amylin
 Slows gastric emptying
 Suppresses glucagon secretion, reducing hepatic
glucose output
 Centrally modulates appetite and satiety
 Used when other drugs have not achieved adequate
glucose control
 Subcutaneous injection
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Injectable Antidiabetic Drugs:
Mechanism of Action (cont’d)

Incretin mimetic

Mimics the incretin hormones
 Enhances glucose-driven insulin secretion from beta
cells of the pancreas
 Only used for type 2 diabetes
 Exenatide: Injection pen device
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Injectable Antidiabetic Drugs:
Adverse Effects

Amylin agonist


Nausea, vomiting, anorexia, headache
Incretin mimetics

Nausea, vomiting, and diarrhea
 Rare cases of hemorrhagic or necrotizing pancreatitis
 Weight loss
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Hypoglycemia


Abnormally low blood glucose level (below
50 mg/dL)
Mild cases can be treated with diet—higher
intake of protein and lower intake of
carbohydrates—to prevent rebound postprandial
hypoglycemia
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Hypoglycemia Symptoms

Early


Confusion, irritability, tremor, sweating
Late

Hypothermia, seizures
 Coma and death will occur if not treated
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Glucose-Elevating Drugs

Oral forms of concentrated glucose



Buccal tablets, semisolid gel
50% dextrose in water (D50W)
Glucagon
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Nursing Implications

Before giving drugs that alter glucose levels,
obtain and document:

A thorough history
 Vital signs
 Blood glucose level, A1C level
 Potential complications and drug interactions
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Nursing Implications (cont’d)

Before giving drugs that alter glucose levels:




Assess the patient’s ability to consume food
Assess for nausea or vomiting
Hypoglycemia may be a problem if antidiabetic drugs
are given and the patient does not eat
If a patient is NPO for a test or procedure, consult
primary care provider to clarify orders for antidiabetic
drug therapy
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Nursing Implications (cont’d)

Keep in mind that overall concerns for any
patient with diabetes increase when the patient:

Is under stress
 Has an infection
 Has an illness or trauma
 Is pregnant or lactating
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Classroom Response Question
A patient with type 1 diabetes is admitted to the medical unit with
an acute exacerbation of chronic obstructive pulmonary disease
(COPD). He is placed on IVPB antibiotics, nebulizer treatments
with albuterol, and an IV corticosteroid, and he is also taking a
proton pump inhibitor for gastrointestinal esophageal reflux
disease (GERD). He takes a dose of glargine insulin every
evening. That evening the nurse notes that his blood glucose
level is 170 mg/dL. The next morning, his fasting glucose level is
202 mg/dL. What is the most likely cause of his elevated glucose
levels?
A.
B.
C.
D.
The albuterol
The antibiotics
The proton pump inhibitor
The corticosteroid
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Nursing Implications (cont’d)

Thorough patient education is essential
regarding:

Disease process
 Diet and exercise recommendations
 Self-administration of insulin or oral drugs
 Potential complications
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Nursing Implications (cont’d)

When insulin is ordered, ensure:

Correct route
 Correct type of insulin
 Timing of the dose
 Correct dosage

Insulin order and prepared dosages are secondchecked with another nurse
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Nursing Implications (cont’d)

Insulin

Check blood glucose level before giving insulin
 Roll vials between hands instead of shaking them to
mix suspensions
 Ensure correct storage of insulin vials
 Only use insulin syringes, calibrated in units, to
measure and give insulin
 Ensure correct timing of insulin dose with meals
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Nursing Implications (cont’d)

Insulin (cont’d)


When drawing up two types of insulin in one syringe,
always withdraw the regular or rapid-acting insulin
first
Provide thorough patient education regarding selfadministration of insulin injections, including timing of
doses, monitoring blood glucose levels, and injection
site rotations
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Classroom Response Question
After the 0700 report, the day shift nurse notices that a patient
has a 0730 dose of insulin due and goes to the automated
dispensing machine to retrieve the insulin. The nurse sees that
the night shift nurse had removed the 0730 dose of insulin, but
the medication administration record (MAR) has not been signed
by the nurse. The patient is confused and says “she thinks” the
night nurse gave her the insulin. The patient’s blood glucose
level is 142 mg/dL. What will the day shift nurse do?
A.
B.
C.
D.
Give the insulin because it was not signed off.
Hold the insulin because the patient thinks she received it and it is
recorded in the machine.
Ask the charge nurse to call the night nurse at home to clarify
whether the insulin was given.
Report this to the nursing supervisor.
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Nursing Implications (cont’d)

Oral antidiabetic drugs





Always check blood glucose levels before giving
Usually given 30 minutes before meals
Alpha-glucosidase inhibitors are given with the first
bite of each main meal
Metformin is taken with meals to reduce GI effects
Metformin will need to be discontinued if the patient is
to undergo studies with contrast dye because of
possible renal effects—check with the prescriber
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Nursing Implications (cont’d)


Assess for signs of hypoglycemia
If hypoglycemia occurs:

Administer oral form of glucose, if the patient is
conscious
 Give the patient glucose tablets or gel, corn syrup,
honey, fruit juice, or nondiet soft drink or have the
patient eat a small snack, such as crackers or a half
sandwich
 Deliver D50W or glucagon intravenously, if the patient
is unconscious
 Monitor blood glucose levels
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Nursing Implications (cont’d)

Monitor for therapeutic response



Decrease in blood glucose levels to the level
prescribed by physician
Measure hemoglobin A1C to monitor long-term
compliance with diet and drug therapy
Monitor for hypoglycemia and hyperglycemia
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Case Study
A male patient who has a history of type 2 diabetes mellitus
is admitted to the medical unit with a diagnosis of
pneumonia. The patient has many questions regarding his
care and asks the nurse why everyone keeps telling him
about hemoglobin A1C. The nurse will inform the patient
that hemoglobin A1C provides information regarding:
A. which type of diabetes the patient has.
B. if he has an infection.
C. patient compliance with treatment regimen for several
months previously.
D. current fasting blood glucose level.
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Case Study
The patient was taking metformin before this
hospitalization. To facilitate better glucose control, the
patient has been switched to insulin therapy while
hospitalized. The patient asks the nurse why it is so
important to time meals with the insulin injection and to give
him an example of a long-acting insulin. Which drug will the
nurse tell the patient is a long-acting insulin?
A.
B.
C.
D.
Insulin glulisine (Apidra)
Insulin isophane suspension (NPH)
Insulin detemir (Levemir)
Regular insulin (Humulin R)
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Case Study
The patient is being discharged home with insulin aspart
(NovoLog) and insulin isophane suspension (NPH). Which
information does the nurse include when providing
discharge teaching to the patient?
A.
B.
C.
D.
Store the insulins in the refrigerator
Shake the insulins for 1 full minute before use.
Administer the injection at a 30-degree angle to your skin.
Draw up the insulin aspart (NovoLog) first, then the insulin
isophane suspension (NPH) into the same syringe.
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Case Study
The nurse enters the patient’s room to complete the
discharge process and finds the patient to be lying in bed
unresponsive and breathing. The patient has a blood
glucose reading of 48 mg/dL. What is the most appropriate
response by the nurse?
A. Place a packet of table sugar in the patient’s mouth.
B. Start CPR.
C. Roll the patient to the side and administer the ordered
glucagon.
D. Have the patient drink orange juice.
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