Chapter 60
Drugs for Diabetes Mellitus
Diabetes Mellitus: Overview of the
Disease and Its Treatment

Disorder of carbohydrate metabolism
 Deficiency of insulin
 Resistance to action of insulin

Sustained hyperglycemia, polyuria, polydipsia,
ketonuria, and weight loss
2
Types of Diabetes Mellitus

Type 1 diabetes (T1DM)
 As a rule, type 1 diabetes develops during childhood
or adolescence, and symptom onset is relatively
abrupt
 Can develop during adulthood
 Accounts for 5% of all cases of diabetes mellitus
 Primary defect is destruction of pancreatic beta cells
due to autoimmune process
 Trigger for this immune response is not entirely
known, but genetic, environmental, and infectious
factors likely play a role
3
Types of Diabetes Mellitus (Cont.)

Type 2 diabetes (T2DM)
 Most prevalent form of diabetes
 Accounts for 90% to 95% of all cases of diabetes
 Affects approximately 22 million Americans
 Insulin resistance and impaired insulin secretion
 Hyperinsulinemia
 Insulin resistance
 Strong family association
4
Complications of Diabetes

Short-term
 Hyperglycemia
 Ketoacidosis
 Hypoglycemia
5
Complications of Diabetes (Cont.)

Long-term
 Macrovascular damage
• Heart disease
• Hypertension
• Stroke
• Hyperglycemia
• Altered lipid metabolism
6
Complications of Diabetes (Cont.)
 Microvascular damage
• Retinopathy
• Nephropathy: Angiotensin-converting enzyme (ACE) inhibitor
or angiotensin II receptor blocker (ARB)
• Sensory and motor neuropathy
• Gastroparesis
• Amputation secondary to infection
• Erectile dysfunction
7
Diabetes and Pregnancy
Before insulin: Virtually all babies born to
severely diabetic women died during infancy
 Factors during pregnancy

 Placenta produces hormones that antagonize the
actions of insulin
 Production of cortisol increases threefold
 Glucose can pass freely from the maternal to the fetal
circulation (fetal hyperinsulinemia)
8
Diabetes and Pregnancy (Cont.)
Proper glucose levels are needed in the
pregnant patient and in the fetus to prevent
teratogenic effects
 Fetal death frequently occurs near term
 Earlier delivery is desirable

9
Diabetes and Pregnancy (Cont.)

Gestational diabetes
 Appears in the mother during pregnancy and subsides
rapidly after delivery
 Managed in much the same manner as any other diabetic
pregnancy
 Blood glucose should be monitored and controlled with
diet and insulin
 Diabetic state usually disappears almost immediately after
delivery
 If diabetic state persists beyond delivery, it is no longer
considered gestational and should be rediagnosed and
treated accordingly
10
Diagnosis of Diabetes
Hemoglobin A1c
 Tests based on glucose:

 Fasting plasma glucose (FPG) test
 Casual plasma glucose test
 Oral glucose tolerance test (OGTT)
11
Prediabetes
Impaired fasting plasma glucose between 100
and 125 mg/dL
 Impaired glucose tolerance test
 Increased risk for developing type 2 diabetes
 May reduce risk with diet changes and exercise
and possibly with certain oral antidiabetic drugs
 Many people who meet criteria for “prediabetes”
never develop diabetes, even if they do not take
precautions against diabetes

12
Overview of Diabetes Treatment
Primary goal is to prevent long-term
complications
 Tight control of blood glucose level is important
 Controlling blood pressure and blood lipids also
is important

13
Type 1 Diabetes
Requires a comprehensive plan
 Integrated program of diet, self-monitoring of
blood glucose, exercise, and insulin replacement

14
Type 1 Diabetes (Cont.)

Dietary measures
 Evidence suggests no ideal percentage of calories
that should be ingested from carbohydrate, fat, or
protein
 Macronutrient distribution for any given individual is
based on the person’s current eating patterns,
preferences, and goals
 Glycemic index
 Substituting low-glycemic-load foods for higherglycemic-load foods may modestly improve glycemic
control
15
Type 1 Diabetes (Cont.)
Physical activity
 Insulin replacement
 Management of hypertension

 An ACE inhibitor (eg, lisinopril) or an ARB (eg,
losartan) can reduce the risk of diabetic nephropathy

Dyslipidemia
 Statins (eg, atorvastatin)
16
Type 2 Diabetes
Similar to type 1, requires comprehensive plan
 Patient should be screened and treated for:

 Hypertension, nephropathy, retinopathy, neuropathy,
dyslipidemias

Glycemic control with:
 Modified diet and physical activity
 Drug therapy
17
Type 2 Diabetes (Cont.)
Step 1
 Step 2
 Step 3
 Step 4

18
Benefits of Glycemic Control
Type 1 diabetes
 Type 2 diabetes

19
Tight Glycemic Control
Inappropriate
Long-standing type 2 diabetes
 Advanced microvascular or macrovascular
complications
 Extensive comorbid conditions
 History of severe hypoglycemia
 Limited life expectancy

20
Monitoring Treatment

Self-monitoring of blood glucose (SMBG)
 Common target values for blood glucose
• 70 to 130 mg/dL before meals
• 100 to 140 mg/dL at bedtime
21
Monitoring Treatment (Cont.)

Hemoglobin A1c
 Also called glycosylated hemoglobin or glycated
hemoglobin
 Provides an index of average glucose levels over the
prior 2 to 3 months
 A1c goal of below 7% is good for most patients
 Goal below 8% may be appropriate for patients with a
history of severe hypoglycemia, limited life
expectancy, or advanced microvascular or
macrovascular complications
22
Insulin: Physiology
Biosynthesis
 Secretion
 Metabolic actions
 Metabolic consequences of insulin deficiency

 Catabolic mode
 Increased glycogenolysis
 Increased gluconeogenesis
 Reduced glucose utilization
23
Insulin
Preparations: “High alert” agents
 Sources of insulin
 Recombinant DNA technology

 Human insulin: Identical to insulin produced by the
human pancreas
 Human insulin analogs: Modified forms of human
insulin that have the same pharmacologic actions as
human insulin but different time courses
24
Types of Insulin

Short duration: Rapid acting
 Insulin lispro [Humalog]
 Insulin aspart [NovoLog]
 Insulin glulisine [Apidra]

Short duration: Slower acting
 Regular insulin [Humulin R, Novolin R]

Intermediate duration
 Neutral protamine Hagedorn (NPH) insulin

Long duration
 Insulin glargine
 Insulin determir [Levemir]
25
Short-Duration,
Rapid-Acting Insulin

Insulin lispro [Humalog]
 Analog of human insulin
 Rapid onset (10 to 20 minutes)
 Short duration (3 to 5 hours)
 Administered immediately before eating or even after
eating
26
Short-Duration, RapidActing Insulin (Cont.)
Insulin aspart [NovoLog]
 Insulin lispro [Humalog]

 Rapid-acting analog of regular insulin
 Onset: 15 to 30 minutes after subcutaneous (subQ)
injection
 Duration: 3 to 6 hours
 Usual route is subQ via injection or use of an insulin pump
 Acts faster than regular insulin but has a shorter duration
of action
 Should be injected 5 to 10 minutes before meals
27
Short-Duration, RapidActing Insulin (Cont.)

Insulin glulisine [Apidra]
 Synthetic analog of natural human insulin
 Rapid onset (10 to 15 minutes)
 Short duration (3 to 5 hours)
 Should be administered close to the time of eating
28
Short-Duration,
Slower-Acting Insulin

Regular insulin [Humulin R, Novolin R]
 Unmodified human insulin
 Four approved routes: SubQ injection, subQ infusion,
intramuscular (IM) injection (used rarely), and oral
inhalation (approved but not currently used)
 Effects begin in 30 to 60 minutes
 Peak in 1 to 5 hours
 Duration up to 10 hours
 Clear solution
29
Short-Duration, SlowerActing Insulin (Cont.)
 U-100 (100 units/mL)
 U-500 (500 units/mL)
30
Intermediate-Duration Insulin

​NPH insulin [Humulin N, Novolin N]
 Drug is injected twice or 3 times daily to provide
glycemic control between meals and during the night
 NPH insulin is the only one suitable for mixing with
short-acting insulins
 Allergic reactions are possible
 NPH insulins are cloudy suspensions that must be
agitated before administration
 NPH insulins are administered by subQ injection only
31
Long-Duration Insulin

Insulin glargine [Lantus]
 Modified human insulin
 Prolonged duration of action (up to 24 hours)
 Once-daily subQ dosing to treat adults and children
with type 1 diabetes and adults with type 2 diabetes
 Clear solution
32
Long-Duration Insulin (Cont.)

Insulin detemir [Levemir]
 Human insulin analog
 Slow onset and dose-dependent duration of action
 Used to provide basal glycemic control
 Clear, colorless solution
 Dosing: Once or twice daily by subQ injection
 Do not mix with other insulins
 Must not be given IV
33
Insulin Appearance
Except for NPH insulins, all insulins made in the
United States are formulated as clear, colorless
solutions
 NPH insulin is a cloudy suspension
 Patients should inspect their insulin before using
it and should discard the vial if the insulin looks
abnormal

34
Insulin

Concentration
 100 units/mL (U-100)
 500 units/mL (U-500)

Mixing insulins
 NPH with short-acting insulins
 Short-acting insulin drawn first
35
Administration

Subcutaneous injection
 Syringe and needle
 Pen injectors
 Jet injectors

Subcutaneous infusion
 Portable insulin pumps
 Implantable insulin pumps
Intravenous infusion
 Inhalation

36
Storage
Unopened vials should be stored under
refrigeration until needed
 Insulin should not be frozen
 Insulin can be used until the expiration date if
kept in the refrigerator
 After opening, insulin can be kept up to 1 month
without significant loss of activity
 Insulin should be kept out of direct sunlight and
extreme heat

37
Storage (Cont.)
Mixtures of insulin in vials are stable for 1 month
at room temperature and for 3 months under
refrigeration
 Mixtures in prefilled syringes should be stored in
a refrigerator for at least 1 week; they should be
stored vertically with the needle pointing up

38
Insulin: Therapeutic Use

Indications
 Principal: Diabetes mellitus
 Required by all patients with T1DM and by many patients
with T2DM
 Most insulin sold is used by people with type 2 diabetes,
largely because T2DM accounts for 90% to 95% of all
cases of diabetes
 IV insulin for diabetic ketoacidosis
 Gestational diabetes
 Hyperkalemia: Can promote uptake of potassium
 Aids in the diagnosis of growth hormone (GH) deficiency
39
Insulin Therapy of Diabetes
Dosage
 Dosing schedules

 Three dosing schedules
• Twice daily premixed insulin regimen
• Intensive basal/bolus strategy
• Continuous subcutaneous insulin
40
Achieving Optimal Glucose Control
Careful attention to all elements of the treatment
program (diet, exercise, insulin replacement
therapy)
 A defined glycemic target
 Self-monitoring of blood glucose according to the
patient’s individualized management plan
 A high degree of patient motivation
 Extensive patient education
 The responsibility for managing diabetes rests with
the patient

41
Complications of Insulin Treatment
Hypoglycemia: Blood glucose below 70 mg/dL
 Drug interactions

 Blood glucose below 70 mg/dL
• Rapid treatment mandatory
• Conscious patients: Fast-acting oral sugar (eg, glucose
tablets, orange juice, sugar cubes, nondiet soda)
• If swallowing reflex or gag reflex is suppressed:
 Nothing should be given by mouth
 IV glucose or parenteral glucagon is the preferred treatment
42
Complications of
Insulin Treatment (Cont.)
Lipohypertrophy
 Allergic reactions
 Hypokalemia
 Drug interactions

 Hypoglycemic agents
 Hyperglycemic agents
 Beta-adrenergic blocking agents
43
Oral Hypoglycemics

Biguanides
 Metformin [Glucophage]
Sulfonylureas
 Thiazolidinediones (also known as glitazones)

 Rosiglitazone [Avandia]
 Pioglitazone [Actos]

Meglitinides (also known as glinides)
 Repaglinide [Prandin]
 Nateglinide [Starlix]
44
Oral Hypoglycemics (Cont.)

Biguanides
 Metformin [Glucophage]
• Drug of choice for initial therapy in most patients with type 2
diabetes
• Most common side effects: Gastrointestinal (GI) disturbances
• Lactic acidosis, a potentially fatal complication, is rare
• Prevention of type 2 diabetes
• Gestational diabetes
• Polycystic ovary syndrome (PCOS)
• Drug interactions
45
Oral Hypoglycemics (Cont.)

Sulfonylureas
 First oral antidiabetics available
 Promote insulin release
 Can be used only for type 2 diabetes
 Major side effects: Hypoglycemia, weight gain
 First generation
 Second generation
 Cardiotoxicity
 Drug interactions
46
Oral Hypoglycemics (Cont.)

Meglitinides (glinides)
 Repaglinide [Prandin]
• Generally well tolerated
• Adverse effect: Hypoglycemia
• Drug interactions: Gemfibrozil [Lopid]
 Nateglinide [Starlix]
• Pharmacology nearly identical to that of repaglinide
47
Oral Hypoglycemics (Cont.)

Thiazolidinediones (glitazones)
 Reduce glucose levels primarily by decreasing insulin
resistance
 Only indication is type 2 diabetes, mainly as an addon to metformin
 Rosiglitazone [Avandia]: Restricted use
 Pioglitazone [Actos]
48
Oral Hypoglycemics (Cont.)

Pioglitazone [Actos]
 Reduces insulin resistance and may also decrease
glucose production
 Indication: Adjunct to diet and exercise to improve
glycemic control in adults with type 2 diabetes
 Adverse effects: Generally well tolerated; most
common reactions are upper respiratory tract
infection, headache, sinusitis, and myalgia
 Drug interactions
49
Oral Hypoglycemics (Cont.)

Alpha-glucosidase inhibitors
 Act in the intestine to delay absorption of
carbohydrates
 Indication: Type 2 diabetes
 Acarbose [Precose]
• Adverse effects: Frequently causes flatulence, cramps,
abdominal distention, borborygmus, and diarrhea, liver
dysfunction
50
Oral Hypoglycemics (Cont.)
 Miglitol [Glyset]
• Especially effective among Latinos and African Americans
• Adverse effects: Flatulence, abdominal discomfort, and other
GI effects
• Has not been associated with liver dysfunction
51
Oral Hypoglycemics (Cont.)

DPP-4 inhibitors (also called gliptins)
 Promote glycemic control by enhancing the actions of
incretin hormones
 Stimulate glucose-dependent release of insulin
 Suppress postprandial release of glucagon
 Sitagliptin [Januvia]
52
Oral Hypoglycemics (Cont.)
 Saxagliptin [Onglyza]
• Most common adverse effects: Upper respiratory infection,
urinary tract infection, and headache
 Linagliptin [Tradjenta]
 Alogliptin [Nesina]
53
Oral Hypoglycemics (Cont.)

Sodium-glucose co-transporter 2 (SGLT-2)
inhibitors
 Block reabsorption of filtered glucose in the kidney,
leading to glucosuria
 Indication: Type 2 diabetes mellitus
 Canagliflozin [Invokana]
• Side effects: Genital fungal infections in female patients,
urinary tract infections, increased urination
54
Oral Hypoglycemics (Cont.)
 Dapagliflozin [Farxiga]
55
Other Drugs
Colesevelam [Welchol]
 Bromocriptine

56
Non-Insulin Injectable Drugs
Pramlintide
 Amylin mimetic

57
Non-Insulin Injectable
Drugs (Cont.)

GLP-1 receptor agonists (also called incretin
mimetics)
 Slow gastric emptying, stimulate glucose-dependent
release of insulin, inhibit postprandial release of
glucagon, and suppress appetite
 Exenatide [Byetta]
• Adverse effects: Hypoglycemia and gastrointestinal effects,
including pancreatitis
• Drug interactions
58
Non-Insulin Injectable
Drugs (Cont.)
 Liraglutide [Victoza]
• May cause medullary thyroid carcinoma (MTC)
59
Non-Insulin Injectable
Drugs (Cont.)

Amylin mimetics
 Pramlintide [Symlin]
• Reduces postprandial levels of glucose by delaying gastric
emptying and suppressing glucagon secretion
• Adverse effects: Hypoglycemia and nausea, injection-site
reactions
• Drug interactions
60
Acute Complications of
Poor Glycemic Control
Diabetic ketoacidosis (DKA)
 Hyperosmolar hyperglycemic state (HHS)
 Cardinal features of both conditions: Hyperglycemic
crisis and associated loss of fluid and electrolytes
 Both conditions can be life-threatening
 Differences

 Hyperglycemia more severe in HHS
 Ketoacidosis characteristic of DKA, absent in HHS

Treatment of the two disorders is similar
61
Diabetic Ketoacidosis
Severe manifestation of insulin deficiency
 Symptoms evolve quickly within hours or days
 Most common complication in pediatric patients and
leading cause of death
 Characteristics

 Hyperglycemia
 Ketoacids
 Hemoconcentration
 Acidosis
 Coma
62
Diabetic Ketoacidosis (Cont.)

Altered glucose metabolism
 Hyperglycemia
 Water loss
 Hemoconcentration

Altered fat metabolism
 Production of ketoacids
63
Diabetic Ketoacidosis (Cont.)

Treatment
 Insulin replacement
 Bicarbonate for acidosis
 Water and sodium replacement
 Potassium replacement
 Normalization of glucose levels
64
Hyperosmolar Hyperglycemic
State (HHS)
Also called hyperglycemic hyperosmolar
nonketotic syndrome (HHNS)
 Large amount of glucose excreted in urine
 Results in dehydration and loss of blood volume
 Increases blood concentrations of electrolytes
and nonelectrolytes (particularly glucose); also
increases hematocrit
 Blood “thickens” and becomes sluggish

65
HHS (Cont.)
Little or no change in ketoacid levels
 Little or no change in blood pH
 No sweet or acetone-like smell to urine or breath
 Occurs most frequently with type 2 diabetes with
acute infection, acute illness, or some other
stress

66
HHS (Cont.)

Can evolve slowly
 Metabolic changes begin a month or two before signs
and symptoms become apparent
If left untreated, can lead to coma, seizures, and
death
 Management

 Correct hyperglycemia and dehydration with IV
insulin, fluids, and electrolytes
67
Glucagon for Treatment of
Severe Hypoglycemia

Preferred treatment is IV glucose
 Immediately raises blood glucose level

Glucagon can be used if IV glucose is not
available
 Delayed elevation of blood glucose
 Cannot correct hypoglycemia resulting from starvation
• Promotes glycogen breakdown, and the malnourished have
little glycogen left
68
Question 1
A patient is prescribed insulin glargine [Lantus]. Which
statement should the nurse include in the discharge
instructions?
A.
B.
C.
D.
The insulin will have a cloudy appearance in the vial.
The insulin should be injected twice daily (before
breakfast and dinner).
The patient should mix Lantus with the intermediateacting insulin.
The patient will have less risk of hypoglycemic
reactions with this insulin.
69
Question 2
A patient is prescribed NPH insulin. Which statement
should the nurse include in the discharge instructions?
A.
B.
C.
D.
The insulin will have a cloudy appearance in the
vial.
The onset of action is rapid.
The patient should not mix Lantus with short-acting
insulin.
The patient will have no risk of allergic reactions
with this insulin.
70
Question 3
A patient is prescribed metformin. Which statement
about metformin does the nurse identify as true?
A.
B.
C.
D.
Metformin increases absorption of vitamin B12.
Metformin can delay the development of type 2
diabetes in high-risk individuals.
Metformin causes patients to gain weight.
Metformin use predisposes patients to
alkalosis.
71