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CHAPTER 32
Antidiabetic Drugs
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Diabetes Mellitus

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)
 Polyuria
 Polydipsia
 Polyphagia
 Glycosuria
 Unexplained weight loss
 Fatigue
 Hyperglycemia
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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 insulinresistance 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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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



Fasting plasma glucose (FPG) levels higher
than or equal to 110 mg/dL but less than
126 mg/dL may indicate “prediabetes”
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
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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-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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Human-Based Insulins

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)
• Newest
 May be given SC or via continuous SC infusion
pump (but not IV)
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Human-Based 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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Human-Based Insulins (cont’d)

Intermediate-acting

Isophane insulin suspension (also called NPH)
• Cloudy appearance
• Slower in onset and more prolonged in duration than
endogenous insulin
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Human-Based Insulins (cont’d)

Long-acting

glargine (Lantus), detemir (Levemir)
• Clear, colorless solution
• Referred to as basal insulin
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Human-Based Insulins (cont’d)

Combination insulin products
 NPH 70% and regular insulin 30% (Humulin
70/30, Novolin 70/30, Novolog 70/30)
 NPH 50% and regular insulin 50% (Humulin
50/50)
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Sliding-Scale Insulin Dosing




SC short-acting or regular insulin doses adjusted
according to blood glucose test results
Typically used in hospitalized diabetic patients or
those on 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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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


First generation: chlorpropamide (Diabinese),
tolazamide (Tolinase)
Second generation: glimepiride (Amaryl), glipizide
(Glucotrol), glyburide (DiaBeta, Micronase)
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Oral Antidiabetic Drugs (cont’d)

Glinides


Thiazolidinediones



repaglinide (Prandin), nateglinide (Starlix)
pioglitazone (Actos), rosiglitazone (Avandia)
Also known as glitazones
Alpha-glucosidase inhibitors

acarbose (Precose), miglitol (Glyset)
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New Antidiabetic Drugs

Amylin mimetics


pramlintide (Symlin)
Incretin mimetics


exenatide (Byetta)
sitagliptin (Januvia)
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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
 First-generation drugs not used as frequently now
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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)

Amylin mimetic

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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Oral 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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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

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 ALT levels
Alpha-glucosidase inhibitors


Flatulence, diarrhea, abdominal pain
Do not cause hypoglycemia, hyperinsulinemia, or
weight gain
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Oral Antidiabetic Drugs:
Interactions

Sulfonylureas




Hypoglycemic effect increases when taken with
alcohol, anabolic steroids, many other drugs
Adrenergics, corticosteroids, thiazides, others may
reduce hypoglycemic effects
Allergic cross-sensitivity may occur with loop
diuretics and sulfonamide antibiotics
May interact with alcohol, causing a
disulfiram-type reaction
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Oral Antidiabetic Drugs:
Interactions

Amylin mimetics


Concurrent insulin doses need to be reduced
Take one hour before other medications
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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 carbs—
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
physician to clarify orders for antidiabetic drug
therapy
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Nursing Implications (cont’d)

Keep in mind that overall concerns for any
diabetic patient increase when the patient:




Is under stress
Has an infection
Has an illness or trauma
Is pregnant or lactating
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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
second-checked 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 rapidacting 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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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:

If the patient is conscious, give oral form of
glucose
• 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


If the patient is unconscious, give D50W or
glucagon, intravenously
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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