Chapter 32 Antidiabetic Drugs

Chapter 32
Antidiabetic Drugs
Copyright © 2020 Elsevier Inc. All Rights Reserved.

Pancreas
 Located behind stomach
 Both exocrine and endocrine gland
 Produce two hormones that play an important role
in regulation of glucose homeostasis
 Insulin
 Glucagon
 Glycogen
 Excess glucose stored in liver and skeletal muscle tissue
 Glycogenolysis
 Conversion of glycogen into glucose when needed
Copyright © 2020 Elsevier Inc. All Rights Reserved. 2

Insulin
 Direct effect on fat metabolism
 Stimulates lipogenesis and inhibits lipolysis
 Stimulates protein synthesis
 Promotes intracellular shift of potassium and
magnesium into the cells
 Cortisol, epinephrine, and growth hormone work
synergistically with glucagon to counter the
effects of insulin.

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

Diabetes Mellitus (Cont.)
 Signs and symptoms
 Elevated fasting blood glucose (higher than 126 mg/dL)
or a hemoglobin A1C (HbA1C) level greater than or
equal to 6.5%
 Polyuria
 Polydipsia
 Polyphagia
 Glycosuria
 Unexplained weight loss
 Fatigue
 Blurred vision

Type 1 Diabetes Mellitus
 Lack of insulin production or production of
defective insulin
 Affected patients need exogenous insulin.
 Fewer than 10% of all DM cases are type 1.
 Complications
 Diabetic ketoacidosis (DKA)
 Hyperosmolar hyperglycemic syndrome (HHS)

Acute Diabetic Complications
 DKA
 Hyperglycemia
 Ketones in the serum
 Acidosis
 Dehydration
 Electrolyte imbalances
 Approximately 25% to 30% of patients with newly
diagnosed type 1 DM present with DKA.
 HHS

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

Type 2 Diabetes Mellitus (Cont.)
 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, also known as insulin-
resistance syndrome, or syndrome X.

Major Long-Term Complications of
Both Types of Diabetes
 Macrovascular (atherosclerotic plaque)
 Coronary arteries
 Cerebral arteries
 Peripheral vessels
 Microvascular (capillary damage)
 Retinopathy
 Neuropathy
 Nephropathy

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.

Audience Response System
Question #1
A woman who has type 2 DM 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.
NOTE: No input is required to proceed.

Answer to System Question #1
ANS: C
Oral antidiabetic medications are generally not

recommended for pregnant patients because of a
lack of firm safety data. Insulin therapy is the
currently recommended drug therapy for pregnant
women.

Screening for Diabetes
 Prediabetes
 Categories of increased risk for DM
• HbA1C of 5.7% to 6.4%
• Fasting plasma glucose 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

Nonpharmacologic Treatment
Interventions
 Type 1: always requires insulin therapy
 Type 2
 Weight loss
 Improved dietary habits
 Smoking cessation
 Reduced alcohol consumption
 Regular physical exercise

Glycemic Goal of Treatment
 HbA1C of less than 7%
 HbA1C diagnostic criteria;
 <5.7 = Normal
 5.7 to 6.4 = Prediabetes
 >6.5 = Type 2 diabetes
 Fasting blood glucose goal for diabetic patients
of 70 to 130 mg/dL
 Estimated average glucose

Treatment for Diabetes
 Type 1
 Insulin therapy
 Type 2
 Lifestyle changes
 Oral drug therapy
 Insulin when the above no longer provide glycemic
control

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.

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

Insulins (Cont.)
 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

Insulins (Cont.)
 Rapid-acting treatment for types 1 and 2 DM
 Most rapid onset of action (5 to 15 minutes)
 Peak: 1 to 2 hours
 Duration: 3 to 5 hours
 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 (SQ) or via continuous SQ
infusion pump (but not intravenously [IV])

Rapid-Acting Insulins
 Afrezza
 Rapid-acting insulin that is inhaled
 Peak of 12 to 15 minutes
 Short duration of action of 2 to 3 hours
 Administered within 20 minutes before each meal
 Must be given in conjunction with long-acting insulins or
oral diabetic agents (for type 2 DM)
 Side effects: hypoglycemia, cough, and throat pain
 Contraindicated: smokers and those with chronic lung
diseases
 Black box warning regarding the risk of acute
bronchospasms
Short-Acting Insulins
 Short acting
 Regular insulin (Humulin R)
 Routes of administration: IV bolus, IV infusion,
intramuscular (IM), SQ
 Onset (SQ route): 30 to 60 minutes
 Peak (SQ route): 2.5 hours
 Duration (SQ route): 6 to 10 hours

Insulin Dosing and Syringes
 U100
 Standard for most (100 units/mL)
 U200
 Insulin pen
 U300
 Insulin pen
 U500
 Newer concentration for those patients needing very
high doses of insulin
 500 units/mL

Intermediate-Acting Insulins
 Intermediate acting
 Insulin isophane suspension (also called NPH)
• Cloudy appearance
• Often combined with regular insulin
• Onset—1 to 2 hours
• Peak—4 to 8 hours
• Duration—10 to 18 hours

Long-Acting Insulins
 Long acting
 Insulin glargine (Lantus)
• Clear, colorless solution
• Constant level of insulin in the body
• Usually dosed once daily
• Can be dosed every 12 hours
• Referred to as basal insulin
• Onset: 1 to 2 hours
• Peak: none
• Duration: 24 hours
• Toujeo: more concentrated U-300

Long-Acting Insulins (Cont.)
 Long acting (Cont.)
 Insulin detemir (Levemir)
• Duration of action is dose dependent.
• Lower doses require twice-daily dosing.
• Higher doses may be given once daily.
 Insulin glargine (Basaglar)
• Biosimilar insulin
• U100
 Insulin degludec (Tresiba)
• Ultra long acting
• Once daily
• U100 or U200

Question #2
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. Inform the patient of the delay.

B. Check the patient’s blood glucose levels.
C. Call the dietary department to send a tray immediately.
D. Give the patient food, such as cereal and skim milk, and
juice.

ANS: D
Lispro insulin’s onset of action is 15 minutes. It is

essential that a patient with DM eat a meal after
injection. Otherwise, profound hypoglycemia may
result.

Fixed-Combination Insulins
 Fixed combinations
 Humulin 70/30
 Humulin 50/50
 Novolin 70/30
 Humalog Mix 75/25
 Humalog 50/50
 NovoLog 70/30

Fixed-Combination Insulins (Cont.)
 Each contains two different insulins, fixed
combinations
 One intermediate-acting type
 Either one rapid-acting type (Humalog, NovoLog) or
one short-acting type (Humulin)

Sliding-Scale Insulin Dosing
 SQ rapid-acting (lispro or aspart) or short-acting
(regular) insulins are adjusted according to blood
glucose test results.
 Typically used in hospitalized diabetic patients or
those on total parenteral nutrition or enteral tube
feedings
 SQ 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
Basal-Bolus Insulin Dosing
 Preferred method of treatment for hospitalized
patients with DM
 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)

Oral Antidiabetic Drugs
 Used for type 2 DM
 Effective treatment involves several elements.
 Careful monitoring of blood glucose levels
 Therapy with one or more drugs
 Treatment of associated comorbid conditions such as
high cholesterol and high blood pressure

Oral Antidiabetic Drugs (Cont.)
 2013 American Diabetes Association guidelines
 New-onset type 2 DM treatment
 Lifestyle interventions
 Oral biguanide drug metformin
 If lifestyle modifications and the maximum tolerated
metformin dose do not achieve the recommended
HbA1C goals after 3 to 6 months, additional treatment
should be given with a second oral agent, GLP-1
agonist (liraglutide, exenatide, albiglutide, lixisenatide)
or insulin.

Oral Antidiabetic Drugs: Biguanide
 Metformin (Glucophage)
 First-line drug and is the most commonly used
oral drug for the treatment of type 2 DM
 Not used for type 1 DM

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)

Adverse Effects
 Biguanides (metformin)
 Primarily affects gastrointestinal (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

Oral Antidiabetic Drugs: Sulfonylureas
 Second generation: glimepiride (Amaryl), glipizide
(Glucotrol), glyburide (DiaBeta)
 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 level
 Adverse effects: hypoglycemia, hematologic effects,
nausea, epigastric fullness, heartburn, many others

Glinides
 Glinides
 Repaglinide (Prandin), nateglinide (Starlix)
 Indication: type 2 DM
 Action similar to sulfonylureas
 Increase insulin secretion from the pancreas

Adverse Effects
 Glinides
 Adverse effects: headache, hypoglycemic effects,
dizziness, weight gain, joint pain, upper respiratory
infection, or flulike symptoms

Thiazolidinediones (Glitazones)
 Thiazolidinediones (glitazones)
 Pioglitazone (Actos)
 Rosiglitazone (Avandia)
• Only available through specialized manufacturer programs
 Insulin-sensitizing drugs
 MOA:
• Decrease insulin resistance
• “Insulin sensitizing drugs”
• Increase glucose uptake and use in skeletal muscle
• Inhibit glucose and triglyceride production in the liver

Adverse Effects
 Alpha-glucosidase inhibitors
 Flatulence, diarrhea, abdominal pain
 Do not cause hypoglycemia, hyperinsulinemia, or
weight gain

Alpha-Glucosidase Inhibitors
 Acarbose (Precose), miglitol (Glyset)
 Contraindications
 Adverse effects

Mechanism of Action
 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)

Oral Antidiabetic Drugs: Dipeptidyl
Peptidase-IV (DPP-IV) Inhibitors
 Dipeptidyl peptidase-IV (DPP-IV) inhibitors
(gliptins)
 Sitagliptin (Januvia)
 Saxagliptin (Onglyza)
 Linagliptin (Tradjenta)
 Alogliptin (Nesina)

Mechanism of Action
 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.

Adverse Effects
 DPP-IV inhibitors
 Upper respiratory tract infection, headache, and
diarrhea
 Hypoglycemia can occur and is more common if used
in conjunction with a sulfonylurea.

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 DM

Injectable Antidiabetic Drugs
 Amylin agonist
 Pramlintide (Symlin)
 Incretin mimetics
 Exenatide (Byetta)
 Dulaglutide (Trulicity)
 Liraglutide (Victoza)
 Albiglutide (Tanzeum)
 Lixisenatide (Adlyxin)
 Combo agent:
• Soliqua (insulin glargine and lixisenatide)
• Xultophy (insulin degludec and liraglutide)

Injectable Antidiabetic Drugs: Mechanism
of Action
 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
 SQ injection

Injectable Antidiabetic Drugs: Mechanism
of Action (Cont.)
 Incretin mimetic
 Mimics the incretin hormones
 Enhances glucose-driven insulin secretion from beta
cells of the pancreas
 Only used for type 2 DM
 Exenatide: injection pen device

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

Sodium Glucose Cotransporter (SGLT2)
Inhibitors
 Inhibition of SGLT2 leads to a decrease in blood glucose
caused by an increase in renal glucose excretion.
 SGLT2 inhibitors: new class of oral drugs for the
treatment of type 2 DM
 Canagliflozin (Invokana), dapagliflozin (Farxiga), and
empagliflozin (Jardiance)
 Action: work independently of insulin to prevent glucose
reabsorption from the glomerular filtrate, resulting in a
reduced renal threshold for glucose and glycosuria

Sodium Glucose Cotransporter (SGLT2)
Inhibitors (Cont.)
 Other effects: may increase insulin sensitivity
and glucose uptake in the muscle cells and
decrease gluconeogenesis
 Results: improved glycemic control, weight loss,
and a low risk of hypoglycemia

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.

Hypoglycemia Symptoms
 Early
 Confusion, irritability, tremor, sweating
 Late
 Hypothermia, seizures
 Coma and death will occur if not treated.

Glucose-Elevating Drugs
 Oral forms of concentrated glucose
 Buccal tablets, semisolid gel
 50% dextrose in water (D50W)
 Glucagon

Nursing Implications
 Before giving drugs that alter glucose levels,
obtain and document:
 A thorough history
 Vital signs
 Blood glucose level, HbA1C level
 Potential complications and drug interactions

Nursing Implications (Cont.)
 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 the
primary care provider to clarify orders for antidiabetic
drug therapy.

 Keep in mind that overall concerns for any
patient with DM increase when the patient:
 Is under stress
 Has an infection
 Has an illness or trauma
 Is pregnant or lactating

Question #3
A patient with type 1 DM is admitted to the medical unit with an acute
exacerbation of chronic obstructive pulmonary disease. He is placed on
IV piggyback antibiotics, nebulizer treatments with albuterol, and an IV
corticosteroid, and he is also taking a proton pump inhibitor for
gastroesophageal reflux disease. He takes a dose of glargine insulin
every evening. This 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. The albuterol
B. The antibiotics
C. The proton pump inhibitor
D. The corticosteroid

ANS: D
Corticosteroids antagonize the hypoglycemic

effects of insulin, resulting in elevated blood
glucose.

 Thorough patient education is essential
regarding:
 Disease process
 Diet and exercise recommendations
 Self-administration of insulin or oral drugs
 Potential complications

 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.

 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.

 Insulin (Cont.)
 When drawing up two types of insulin in one syringe,
always withdraw the regular or rapid-acting insulin
first.
 Provide thorough patient education regarding self-
administration of insulin injections, including timing of
doses, monitoring blood glucose levels, and injection
site rotations.

Question #4
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 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. Give the insulin because it was not signed off.

B. Hold the insulin because the patient thinks she received it, and it is
recorded in the machine.
C. Ask the charge nurse to call the night nurse at home to clarify whether
the insulin was given.
D. Report this to the nursing supervisor.

ANS: C
Never guess whether a drug was given. Taking the

drug out of the machine does not mean it was
given. The nurse should ask the night nurse what
was done.

 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.

 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 IV if the patient is
unconscious.
 Monitor blood glucose levels.

 Monitor for therapeutic response:
 Decrease in blood glucose levels to the level
prescribed by physician.
 Measure HbA1C to monitor long-term compliance
with diet and drug therapy.
 Monitor for hypoglycemia and hyperglycemia.

Case Study
A male patient who has a history of type 2 DM 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 HbA1C.
1. What can the nurse inform the patient about the use of
HbA1C in diabetes mellitus?
A. Helps to identify which type of DM the patient has

B. Will identify if he has an infection
C. Will aid in monitoring patient compliance with treatment
regimen for several months previously
D. Represents current fasting blood glucose level
Answer to Case Study Question #1
ANS: C
HbA1C is a good indicator of the patient’s

compliance with the therapy regimen for several
months previously.

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.
2. Which drug will the nurse tell the patient is a long-acting
insulin?
A. Insulin glulisine (Apidra)

B. Insulin isophane suspension (NPH)
C. Insulin detemir (Levemir)
D. Regular insulin (Humulin R)
ANS: C
The nurse should inform the patient that timing of meals

with insulin and oral antidiabetic therapy is important to
prevent hypoglycemia and to obtain the most optimal
results from the antidiabetic therapy. Whereas insulin
detemir (Levemir) is a long-acting insulin, insulin
glulisine (Apidra) is a rapid-acting insulin. Insulin
isophane suspension (NPH) is an intermediate-acting
insulin, and regular insulin (Humulin R) is a short-acting
insulin.
Case Study
The patient is being discharged home with insulin aspart
(NovoLog) and insulin isophane suspension (NPH).
3. Which information does the nurse include when providing
discharge teaching to the patient?
A. Store the insulins in the refrigerator.

B. Shake the insulins for 1 full minute before use.
C. Administer the injection at a 30-degree angle to your skin.
D. Draw up the insulin aspart (NovoLog) first and then draw up
the insulin isophane suspension (NPH) into the same
syringe.

ANS: D
The rapid-acting (clear) and then the intermediate-

acting (cloudy) insulins should be mixed in the syringe
after the appropriate amount of air has been injected.
Insulin is stored at room temperature when it will be
used within the month. The injection should be
administered at a 90-degree angle for patients who
have adequate body fat and at a 45-degree angle for
patients who are very thin. Insulins should be rolled
before administration and not shaken.
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.
4. What is the most appropriate response by the nurse?
A. Place a packet of table sugar in the patient’s mouth.

B. Start cardiopulmonary resuscitation (CPR).
C. Roll the patient to the side and administer the ordered
glucagon.
D. Have the patient drink orange juice.

ANS: C
Glucagon, a natural hormone secreted by the pancreas,

is available as an SQ injection to be given when a quick
response to severe hypoglycemia is needed. Because
glucagon injection may induce vomiting, roll an
unconscious patient onto his or her side before injection.
Glucagon is useful in unconscious hypoglycemic
patients without established IV access. The patient is at
risk for aspiration, so nothing should be administered by
mouth. CPR is not indicated.

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A. She should continue the antidiabetic medication at the

NOTE: No input is required to proceed.

Oral antidiabetic medications are generally not

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A. Inform the patient of the delay.

NOTE: No input is required to proceed.

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Lispro insulin’s onset of action is 15 minutes. It is

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