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10
E
D
LISA B. COHEN, CHRISTINE EISENHOWER,
and ANNE L. HUME
L O
1. Identify the prevalence and clinical presentation of endocrine disorders, including diabetes mellitus, obesity,
thyroid disorders, and sexual dysfunction, among older adults.
2.
Evaluate the management of older adults with endocrine disorders compared to younger patients.
3. Assess the potential effects of major endocrine disorders on common comorbid diseases in older adults and on
quality-of-life issues.
4.
Critique major studies of diabetes mellitus that enrolled older adults regarding the studies’ application to clinical
practice.
5.
Develop a treatment plan appropriate for older adults with selected endocrine disorders.
K T D
GRAVES’ DISEASE: An immune system disorder characterized by painful, red eyes due to inflammation.
Eyelids and tissues around the eyes are swollen with the eyeballs bulging out of their sockets.
HEMOGLOBIN A
1c
(HbA
1c
): A minor component of hemoglobin to which glucose is bound. HbA
1c
is also referred
to as glycated hemoglobin; it provides a measure of glucose control over the past 3 months.
HORMONE THERAPY (HT): A term, along with menopausal hormone therapy, that describes the hormones
used to treat menopausal symptoms. In the past, this therapy was called hormone replacement therapy. The
newer term reflects the fact that the estrogen and progestin concentrations are not returned to premenopausal
levels.
MACROVASCULAR COMPLICATIONS: Diseases of the larger blood vessels resulting in atherosclerotic vascular
disease.
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| Fundamentals of Geriatric Pharmacotherapy
MICROALBUMINURIA: Urinary albumin excretion between 30 and 300 mg in a 24-hour period.
MICROVASCULAR COMPLICATIONS: Diseases of the small blood vessels that may lead to loss of sensation
and foot ulcers.
SECRETAGOGUES: A substance or hormone that causes or stimulates secretion.
T3 (TRIIODOTHYRONINE): An iodine-rich thyroid hormone formed from one molecule of monoiodotyrosine and
one of diiodotyrosine. Most of the circulating T3 is the result of the enzymatic degradation of T4 in extrathy-
roidal peripheral tissues. T3 is extensively bound to albumin, thyroxine-binding globulin, and transthyretin.
T4 (THYROXINE): An iodine-rich thyroid hormone formed from two molecules of diiodotyrosine in the thyroid
gland. T4 is extensively bound to albumin, thyroxine-binding globulin, and transthyretin.
THYROIDITIS: An inflammation of the thyroid gland in which there is a release of thyroid hormone that results
in a temporary hyperthyroid state.
THYROID-STIMULATING HORMONE (TSH): A hormone secreted by the pituitary gland; stimulates thyrotropin
receptors to regulate the activity of the thyroid gland.
I
T
he endocrine system affects almost every
organ in the body physiologically. It regu-
lates glucose and thyroid metabolism, maintains
muscle and skeletal mass and normal gonadal
functioning, and has many other roles. Similar
to other systems, the endocrine system may
undergo diverse changes due to aging. The
best recognized age-related endocrine change
occurs within the hypothalamic-pituitary-adrenal
axis with the onset of menopause in middle-aged
women. The secretion of growth hormone and the
serum concentration of insulin-like growth factor
may decrease with age.
1
The secretion of dehy-
droepiandrosterone from the adrenal cortex may
also decline with advancing age,
and older adults
may have greater variability in serum cortisol
concentrations throughout a 24-hour period.
2,3
Although the secretion of other hormones may
differ in older versus younger adults, whether
the differences are truly age-related or are due
instead to disease-related processes is diffi-
cult to establish. Endocrine diseases such as
diabetes mellitus and thyroid disorders together
affect about 12% of Americans. This chapter will
focus on diabetes mellitus, obesity, thyroid disor-
ders, sexual dysfunction, and other endocrine
diseases in older adults.
D M
Etiology, Epidemiology, and
Clinical Presentation in Older
Adults
According to the Centers for Disease Control and
Prevention, the prevalence of diabetes has risen
to almost 27% of people 65 and older.
4
Because
its prevalence increases with advancing age,
diabetes will become even more common with
the aging of the American population. Interest-
ingly, nondiabetic patients have been noted to
have higher hemoglobin A
1c
(HbA
1c
) levels as
they age.
The HbA
1c
levels have been reported to
increase 0.012% per year.
5
Also, the prevalence
of diabetes continues to rise among minority
groups.
6
Among older adults with diabetes,
about 40% were diagnosed at 65 or older.
7
Patients with type 1 diabetes have increased
their life expectancy and, as a result, more older
adults will have type 1 diabetes in the near future.
Case reports of older adults diagnosed with type
1 diabetes have been published,
although the
true prevalence of type 1 diabetes in the older
adults remains uncertain.
8
An estimated 35% of adults have predia-
betes, and this estimate increases to more
than 50% in individuals over 65 years of age.
4
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259
Diabetes, both diagnosed and undiagnosed,
is present in 8.3% of Americans. This figure
increases to 26.9% among people over 65 (see
Figure 10-1).
4,9
The American Diabetes Asso-
ciation (ADA) recommends screening all adults
over 45 for diabetes every 3 years. About 20% to
25% of patients in this age group have impaired
glucose tolerance and a twofold increase in the
risk of mortality from macrovascular complica-
tions.
10
Older adults with diabetes, compared
to individuals of the same age who do not have
the disease, are two to three times more likely
to report an inability to walk a quarter mile or to
perform activities such as climbing stairs, using
a cane or walker, or doing housework.
9
The etiology of type 2 diabetes includes
both genetic and environmental factors, with
obesity and physical inactivity comprising the
latter group. Several genes have been identi-
fied as increasing the risk of developing type
2 diabetes independently of environmental
factors.
11
Predictors for the development of
type 2 diabetes include a reduction in insulin
secretion, insulin resistance, elevated body
mass index (BMI), being a current smoker, and
elevated liver enzymes.
12
Insulin resistance is
the result of increased inflammation secondary
to high concentrations of free fatty acids and
tumor necrosis factor-α, an increase in obesity,
increasing age, and decreased physical
activity.
12
Several factors increase the likelihood
of older adults developing type 2 diabetes. One
age-related factor in diabetes is the alteration of
insulin secretion in response to an oral glucose
load.
13
Older adults may also have an increase
in insulin resistance due to central obesity, high
saturated fat intake, and inactivity. The poor food
choices in some older individuals may be due
to financial stressors and an inability to chew
certain foods. Research has identified differ-
ences between older obese and lean individuals.
Although older adults with diabetes often have
normal hepatic glucose production, lean older
adults may have decreased insulin secretion
but normal insulin-mediated glucose disposal.
14
These patients have been referred to as having
diabetes type 1½.
14,15
Conversely, obese older
adults with diabetes often have normal insulin
secretion but increased insulin resistance.
14
Older adults with diabetes may not have the
typical symptoms of hyperglycemia. As people
age, the renal threshold for glucose increases
and, as a result, older persons may not have
the polyuria and nocturia that younger patients
Figure 10-1. Estimated prevalence of diagnosed and undiagnosed diabetes in people age 20 years or older, by age group, United
States, 2005–2008.
Source: 2005–2008 National Health and Nutrition Examination Survey. For more information, see National Diabetes Fact Sheet, 2011.
http://www.cdc.gov/diabetes/pubs/pdf/ndfs_2011.pdf
26.9%
13.7%
3.7%
20–44 45–64 >65
AGE GROUP
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| Fundamentals of Geriatric Pharmacotherapy
may experience.
11
In addition, the normal thirst
mechanism declines with advancing age. Older
persons may have only vague symptoms of
fatigue, weight loss, vision disturbances, urinary
incontinence, or other symptoms that are easily
mistaken for common comorbid conditions.
11
Older adults with diabetes may have an abnormal
random glucose as their only presenting sign of
diabetes.
KEY POINT:
Older patients often
lack the classic symptoms of diabetes and
instead present with urinary incontinence,
confusion, and fatigue, which may
be confused with other diseases.
Summary of Standard Treatment
Based on the ADA clinical practice guidelines,
the recommended optimal glycemic control for
an adult with diabetes is to achieve an HbA
1c
<7%; a less stringent goal of <8% may be appro-
priate for older patients.
16
This would include
preprandial glucose concentrations between 70
and 130 mg/dL and postprandial concentrations
<180 mg/dL.
16
Although a target HbA
1c
of <6%
may reduce some diabetes-related complica-
tions, the risk of hypoglycemia increases. Recent
trials have shown that targeting HbA
1c
to normal
levels (below 6%) may increase the risk of cardio-
vascular complications as well as increased
hypoglycemic episodes or have no significant
benefit.
17-19
The recommended goal blood pres-
sure in patients with diabetes is <130/80 mmHg.
16
Overall treatment should include medical nutrition
therapy (MNT), metformin with lifestyle changes
such as MNT and exercise, and early insulin initi-
ation, if necessary. Table 10-1 summarizes the
standard drug therapies for diabetes as well as
other endocrine disorders.
Treatment Recommendations for
Older Adults
Potential quality-of-life issues for older adults with
diabetes should be acknowledged when devel-
oping a treatment plan that may be complicated
and expensive. An older person who is cogni-
tively intact and otherwise independent in activi-
ties of daily living should have a target HbA
1c
of
<7%. Frail older persons with a life expectancy
of <5 years or individuals at otherwise high risk of
adverse outcomes from hypoglycemia may have
a higher goal, such as an HbA
1c
<8%, provided
the risk of acute hyperglycemia is reduced.
6,16
The ADA recommends providing patients the
estimated average glucose as well as the HbA
1c
when reporting results to allow them to reflect on
the similarity of blood glucose readings that they
would do with home monitoring. The diabetic
complication with the highest morbidity and
mortality is cardiovascular disease. The 2013
updated American Geriatric Society Panel on
Improving Care for Elders with Diabetes indi-
cated that most older persons who have diabetes
also benefit from treatment of their hypertension
and dyslipidemia, if present.
6
Aiming for systolic
blood pressure of <130 mmHg does not have
better cardiovascular outcomes compared
to systolic blood pressure between 130 and
140 mmHg.
20
The use of low-dose aspirin for
primary prevention should also be considered
on an individual basis.
KEY POINT:
Older patients must
have individualized treatment goals
that take into consideration their life
expectancy, comorbid conditions, level of
frailty, acute risk of hypoglycemia, care
setting, and quality-of-life issues.
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261
Table 10-1. Endocrine Treatments and Geriatric Considerations
Medication Examples
General Adult Treatment
Principles Geriatric Considerations
Drugs Used in Diabetes Treatment
Miglitol (Glyset)
Acarbose (Precose)
Monotherapy adjunct to diet to
improve glycemic control in type 2
diabetes.
May be used in combination therapy
with a sulfonylurea.
No specific trials in older adults have been
conducted in patients on acarbose.
Dosage adjustments not necessary.
Elderly patients had 1.5 times serum
concentrations compared to younger adults.
Metformin (glucophage) Monotherapy for type 2 diabetes
or used concomitantly with a
sulfonylurea or insulin to improve
glycemic control.
AUC and half-life increased in elderly. Initial
dose and maintenance dosing should be
conservative.
Should not titrate to maximum dosage.
Not recommended to use in elderly patients
(≥80).
Sitagliptin (Januvia)
Saxagliptin (Onglyza)
Monotherapy for type 2 diabetes or in
combination with other antidiabetic
agents.
One clinical trial showed no difference in
safety or efficacy compared to younger
adults; less risk of hypoglycemia than other
medications.
Exenatide (Byetta) Adjunctive treatment of type 2
diabetes in patients receiving
sulfonylurea, metformin, or TZD or a
combination of these medications.
Not recommended in patients with creatinine
clearance <30 mL/min; less risk of
hypoglycemia than other medications.
Repaglinide (Prandin)
Nateglinide (Starlix)
Monotherapy for type 2 diabetes or
adjunctive therapy in patients on
metformin or TZD.
No changes in safety and efficacy were seen
in patients ≥65 on nateglinide.
One trial showed that patients ≥65 taking
repaglinide had less hypoglycemia
compared to a sulfonylurea.
Glyburide (Micronase,
Diabeta)
Glipizide (Glucotrol)
Glimepiride (Amaryl)
Chlorpropamide (Diabinese)
Tolbutamide (Orinase)
Tolazamide (Tolinase)
Management of type 2 diabetes
May be used as monotherapy or in
combination with metformin or
insulin.
Differences between each sulfonylurea.
May cause rapid and prolonged hypoglycemia
despite glucose administration.
Use with caution in patients with renal
insufficiency.
Glipizide preferred because of fewer
drug interactions and elimination is not
dependent on renal function.
Chlorpropamide and glyburide are not
recommended in the elderly.
Pioglitazone (Actos)
Rosiglitazone (Avandia)
Monotherapy for type 2 diabetes
or in combination therapy with
sulfonylureas, metformin, or insulin.
Rosiglitazone is not recommended in
combination with insulin.
No dosage adjustments recommended with
either rosiglitazone or pioglitazone; with
rosiglitazone, may be an increased risk of
fractures in hand, upper arm, and foot.
Rosiglitazone should be used cautiously in
patients with low bone density or history of
fractures or falls.
Various insulins Treatment of type 1 or type 2
diabetes.
Initial doses may require consideration for
renal function; elderly may need assistance
to draw up insulin in a syringe due to
dexterity and vision issues.
May need to use prefilled syringes or
pen devices; patient must recognize
hypoglycemic and hyperglycemic
symptoms.
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| Fundamentals of Geriatric Pharmacotherapy
Sodium-glucose
cotransporter 2 inhibitors
Canagliflozin (Invokana)
Dapagliflozin (Farxiga)
Management of type 2 diabetes. Canagliflozin: Should not be used in patients
with an estimated glomerular filtration rate
(GFR) of <45 mL/min. If GFR = 45–60 mL/
min, maximum dose is 100 mg daily.
Dapagliflozin: Not recommended for use in
patients with GFR <60 mL/min.
Drugs Used for Weight Loss/Control
Orlistat (Xenical, over-the-
counter Alli)
Used with reduced-calorie diet to
promote and maintain weight loss.
Contraindicated in cholestasis and
chronic malabsorption syndrome.
May interact with anticonvulsants,
cyclosporine, levothyroxine, and
warfarin.
Most studies excluded older adults.
May cause or worsen fecal incontinence.
May lead to deficiency of fat-soluble vitamins.
Lorcaserin (Belviq) May interact with SSRIs, SNRIs,
MAOIs, triptans, bupropion,
dextromethorphan, and St. John’s
wort.
Risk of serotonin syndrome.
Has not been studied in individuals
using insulin.
Risk of cognitive impairment.
Long-term effects on cardiovascular morbidity
and mortality are unknown.
Phentermine and topiramate
extended release (Qsymia)
Controlled substance.
May interact with nonpotassium-
sparing diuretics, and CNS
depressants.
Adverse effects include dizziness,
insomnia, constipation, dry mouth,
paresthesias, and dysgeusia.
Contraindicated in glaucoma, hyperthyroidism,
with MAOIs.
Risk of cognitive impairment, tachycardia,
metabolic acidosis, increased serum
creatinine.
Long-term effects on cardiovascular morbidity
and mortality are unknown.
Drugs for Thyroid Disorders
Methimazole (Tapazole)
Propylthiouracil
Adverse effects include rash, urticaria,
arthralgias, hepatotoxicity, and
agranulocytosis (<0.5 %).
Older adults may be at increased risk of
agranulocytosis.
Levothyroxine
(Synthroid, Tirosint)
Triiodothyronine (Cytomel)
T3 and T4
(Liotrix)
Dessicated thyroid
(Armour thyroid)
Levothyroxine (T4) preferred because
of its stable conversion to T3
and half life of 4–7 days. T3 has
a shorter half-life and requires
multiple daily dosages.
Combination T3 and T4 products
are more expensive and require
monitoring of both T3 and T4
concentrations, unlike levothyroxine
preparations.
Dessicated thyroid has had
standardization problems as well as
adverse cardiac effects.
3
Primary concern is the precipitation of
cardiac events when beginning replacement
therapy.
Dosages should be started low (i.e.,
levothyroxine 12.5–25 mcg once daily)
and gradually titrated upward, especially in
presence of known CVD.
Table 10-1. (cont’d)
Medication Examples
General Adult Treatment
Principles Geriatric Considerations
Drugs Used in Diabetes Treatment
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263
Individualization of Treatment in
Type 2 Diabetes
Treatment of older adults with diabetes is similar
to that of younger patients and involves the
same stepwise approach.
19,20
Nonpharmaco-
logic treatments (e.g., diet and exercise) should
be tailored to the individual. An older adult who
is malnourished will need adequate calories
and protein. The presence of comorbid condi-
tions such as severe cardiovascular disease and
mobility problems will require careful consider-
ation in the development of an exercise plan. An
interdisciplinary team that includes a dietitian
or nutritionist, as well as a physical therapist, is
important in developing an optimal care plan.
The selection of drug therapy requires consid-
eration of goals and the presence of comorbid
conditions, especially in the frail individual (see
Table 10-2). A primary consideration in selecting
drug therapy is the risk of hypoglycemia, such as
a patient with impaired kidney function or incon-
sistent oral calorie intake. A patient with cogni-
tive impairment may not be able to communicate
symptoms of hypoglycemia. Other considerations
include life expectancy, baseline glycemic control,
adverse effects, tolerability, and previous diabetes
medication use.
19
For example, an older adult with
previous falls and hospital admissions secondary
to sulfonylurea therapy should be switched to
drugs with a lower potential for hypoglycemia.
Biguanides, thiazolidinediones, alpha-glucosi-
dase inhibitors, glucagon-like peptide-1 receptor
agonists (GLP-1 agonists), sodium-glucose
cotransporter 2 inhibitors, and dipeptidyl pepti-
dase IV inhibitors generally do not cause hypogly-
cemia unless used in combination with drugs that
stimulate insulin release.
21,22
Diabetes mellitus generally requires addi-
tional medications over time to maintain glycemic
control. Additional medications should be
considered within 2 to 3 months after initiation
of a therapy or any time that the HbA
1c
is not at
an individual’s goal. Lifestyle interventions are
essential and may significantly decrease hyper-
glycemia.
23
Implementing lifestyle changes such
as weight loss and exercise programs may also
improve hypertension and dyslipidemias. Life-
style recommendations must be tailored to the
individual’s functional status, level of frailty, and
comorbid conditions. The risks of exercise in
older patients may include musculoskeletal inju-
ries or worsening foot ulcers or wounds, so the
exercise plan should be carefully developed.
Common Oral Medications
Along with lifestyle interventions, metformin is the
preferred initial therapy for type 2 diabetes. The
Drugs for Sexual Dysfunction
Sildenafil (Viagra)
Tadalafil (Cialis)
Vardenail (Levitra)
Avanafil (Stendra)
PDE-5 inhibitors are considered
first-line treatment for erectile
dysfunction when contributing
factors for ED have been evaluated;
generally safe.
Older men should be evaluated for use of
nitrates (and other potentially interacting
drugs) as well as for overall CVD before
using PDE-5 inhibitors.
Estrogen therapy (various
vaginal estrogen products)
Ospemifene (Osphena)
When symptoms of dyspareunia
persist in peri- or postmenopausal
women despite the appropriate use
of vaginal lubricants and moisturizers,
vaginal estrogen products and oral
ospemifene may give relief.
The long-term safety of ospemifene in older
women is unclear.
Transdermal and oral estrogen products
should not be started late into menopause
(≥10 yr after menopausal transition) or in
women over 60.
AUC, area under curve; CNS, central nervous system; CVD, cardiovascular disease; ED, erectile dysfunction; MAOI,
monoamine oxidase inhibitor; PDE-5, phosphodiesterase-5; SNRI, serotonin–norepinephrine reuptake inhibitor; SSRI,
selective serotonin reuptake inhibitor; TZD, thiazolidinedione.
Table 10-1. (cont’d)
Medication Examples
General Adult Treatment
Principles Geriatric Considerations
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Table 10-2. Comparison of Pharmacotherapy Options for Type 2 Diabetes in Older Adults
Medication Advantages Disadvantages
Metformin Hypoglycemia (adverse effect) usually
does not occur if monotherapy
May help with weight loss
May be beneficial to lipid profile
Available as a generic drug
May improve insulin resistance
Generally, should not be dosed to
maximum in older adults
Gastrointestinal side effects may be
common
Rare risk of lactic acidosis
Should not use in patients with moderate-
severe heart failure because of risk of
lactic acidosis
Sulfonylureas Least expensive, available generically
Works well in lean patients
High risk of hypoglycemia
Weight gain
Thiazolidinediones No hypoglycemia if monotherapy
Improves insulin resistance
Weight gain
Edema
Expensive
Increased risk of fractures of the hand,
upper arm, and foot
Risk of cardiovascular events with
rosiglitazone
Alpha-glucosidase inhibitors No hypoglycemia if monotherapy
No weight gain
Lowers postprandial glucose levels
High incidence of gastrointestinal side
effects
Hypoglycemia must be treated with
dextrose or lactose
Weak, lowers HbA
1c
0.5%
Must be dosed prior to each meal
Meglitinides
Slight decreased risk of hypoglycemia
compared to sulfonylureas
Reduces postprandial glucose levels
Expensive
Risk of hypoglycemia
Must be taken with each meal; multiple
doses
Weight gain
Dipeptidyl peptidase IV
inhibitors
No hypoglycemia if monotherapy
Few side effects
Use with caution in renal impairment
Weak, lowers HbA
1c
0.5%
Expensive
Incretin mimetics No hypoglycemia if monotherapy Injectable
Nausea, vomiting
Expensive
Should not use in patients with creatinine
clearance <30 mL/min
Amylin analog Effective at lowering blood glucose
levels
High risk of hypoglycemia
Must be used with insulin
Expensive
Injectable
Bromocriptine No hypoglycemia if monotherapy Weak
Expensive
Hypotension may occur
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drug decreases hepatic glucose production
and increases insulin sensitivity. In general,
metformin is well tolerated if titrated slowly
upward. The drug has the potential advantage of
causing weight loss, which may benefit the lipid
profile. In addition, a systematic review indicated
that the use of metformin may decrease the risk
of cardiovascular mortality in older adults.
7
Several precautions exist when using
metformin in older adults (Table 10-2). Metformin
may have a reduced total body clearance
and has a prolonged half-life in older patients.
Data obtained from relatively younger subjects
have shown that metformin may be used until the
glomerular filtration rate falls below 30 mL/min.
21,24,25
Although clinically significant responses to
metformin usually occur at dosages over
1500 mg daily, the dosage should not be
increased to the maximum because of the
potential risk for lactic acidosis in older adults
with impaired kidney function. Metformin should
be used only after careful calculation of the
creatinine clearance and after ensuring that
it is >30 mL/min.
21
Dosages should be titrated
more slowly than in younger adults to lessen the
loss of appetite, stomach upset, and diarrhea
to which older adults may be more sensitive.
In addition, a study of older adults comparing
glipizide and metformin showed that, while the
drugs were equally effective, metformin caused
weight loss, whereas glipizide caused weight
gain.
26
Vitamin B12 deficiency is associated with
chronic metformin use in older adults due to its
effect on ileal absorption of the vitamin; its use
may be overlooked as a potential contributing
factor for vitamin B12 deficiency and should be
supplemented with B12 injections as compared
to oral therapy.
27
KEY POINT:
Patients should begin
diabetes control with lifestyle changes,
individualized to their own needs,
and then start metformin therapy if
their kidney function is adequate.
First- and second-generation sulfonylureas
are equally effective and are available as generic
drug products. In general, glyburide, glipizide,
and glimepiride are preferred. Glyburide may
accumulate in impaired kidney function; a meta-
analysis comparing glyburide with other secre-
tagogues showed an increased risk of hypo-
glycemia with the drug.
28,29
Patients should be
started on the lowest dose, such as glipizide
2.5 mg per day, and increased by 2.5–5 mg
every 1–2 weeks. Some first-generation sulfonyl-
SGLT2 inhibitors Low risk of hypoglycemia if
monotherapy
Lowers HbA
1c
about 1%
May cause small weight loss
Use caution in renal impairment
Increased risk of mycotic infections
May cause hypotension due to
intravascular depletion
May cause hyperkalemia
Expensive
Bile acid sequestrant Low risk of hypoglycemia if
monotherapy
Effective in lowering cholesterol and
LDL-C
Expensive
Drug interactions
May cause constipation
Insulin Relatively inexpensive
Effective at lowering blood glucose
levels
High risk of hypoglycemia
Injectable
Table 10-2. (cont’d)
Medication Advantages Disadvantages
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| Fundamentals of Geriatric Pharmacotherapy
ureas require more frequent dosing and others
have longer half-lives, such as chlorpropamide,
which significantly increases the risk of hypogly-
cemia. These drugs are not optimal choices for
older adults with diabetes.
The thiazolidinediones (TZDs), pioglitazone
and rosiglitazone, act by improving insulin resis-
tance. Pioglitazone is preferred because rosi-
glitazone has been shown to increase the risk
of myocardial infarction (MI) but not increase
the risk of cardiovascular mortality or death from
other causes.
30,31
The use of rosiglitazone should
be avoided in older adults because of the higher
prevalence of cardiovascular diseases, such as
MI and heart failure. Pioglitazone is effective in
the treatment of type 2 diabetes in older adults
and may also have a beneficial effect on lipids.
Pioglitazone should be started at a dosage of
15–30 mg per day and titrated to a maximum of
45 mg daily. The beneficial effects of pioglitazone
may take at least several weeks. Adverse effects
with TZDs include weight gain, edema, osteo-
penia that could lead to fractures, and a twofold
increase in the risk of heart failure. These drugs
should generally be avoided in older adults with
heart failure.
21
KEY POINT:
Maintenance dosages
of sulfonylureas in older adults should be
on the lower end of the recommended
range because of both pharmacokinetic
and pharmacodynamic alterations
aecting outcomes with these drugs.
Insulin
If a patient’s diabetes does not respond to
combinations of oral medications, insulin should
be considered. In the past, the initiation of insulin
was delayed for years after diagnosis or for very
poor glycemic control. Often, insulin is deferred
because of a perception that older adults are
unable to manage this therapy. Insulin can
be used safely in older adults by initiating the
therapy slowly and titrating carefully. Treatment
with insulin and additional medications are now
recommended within 2–3 months of failed mono-
therapy.
21
Newer basal insulin products such as
insulin glargine may have advantages in older
adults, but they have not been studied in these
patients.
Basal insulin may be added to oral combi-
nation therapy in older adults. For example, inter-
mediate-acting neutral protamine Hagedorn (NPH)
insulin may be initiated at 10 units daily in addi-
tion to combination treatment with metformin and
glipizide. The insulin dosage can be titrated up
by 1–2 units every 3 days to avoid hypoglycemia
and maintain premeal and bedtime blood glucose
concentrations of 80–140 mg/dL. Although titrating
insulin NPH to achieve an HbA
1c
of <7% may
take several weeks to months, an HbA
1c
of <8%
may be achieved sooner. Basal or bolus insulin
can be added to the regimen with continued
monitoring.
21
If basal insulin therapy becomes
inefficient or the targets are not achievable, the
patient may alter his or her insulin regimen with
basal and bolus combinations in fixed regimens
(i.e., insulin 70/30 twice daily therapy) or multiple
daily doses of insulin (i.e., insulin glargine daily
with mealtime boluses of insulin lispro). Moni-
toring hypoglycemia is especially important
in older adults because hypoglycemia may
increase risk of falls.
KEY POINT:
Insulin treatment should
be considered when the HbA
1c
remains
above the desired goal despite combination
therapy with the recommended dosages.
Assistive devices for insulin therapy may
help older patients with vision, hearing, and
dexterity problems successfully manage their
therapy. One product attaches to an insulin
syringe to magnify the markings on the syringe
for those with impaired vision. Insulin pen
devices have also made insulin delivery easier
for individuals who are visually impaired or who
have dexterity problems, although even pen
devices may still be difficult to manage. For frail
skin, shorter pen needles are available and do
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