Download TYPE 2 DIABETES MELLITUS: EXISTING DISEASE

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TYPE 2 DIABETES MELLITUS:
EXISTING DISEASE
Establishing Optimal Control . . . . . . . . . . . . . . . . . . . . Level II
Margaret A. Robinson, PharmD
CASE SUMMARY
A 45-year-old woman comes to the pharmacy for an education class
about diabetes taught by the pharmacist. She was diagnosed with
diabetes 6 months ago and started on therapy along with lifestyle
modifications. The patient’s blood glucose levels and A1C have
worsened, and the patient is not maintaining her lifestyle modifications. Her drug regimen for diabetes and lifestyle modifications will
need to be changed. Because of diabetes and obesity, her cholesterol
and blood pressure are uncontrolled. The reader will have to create
a treatment plan that optimizes control of the patient’s hypertension and dyslipidemia as well.
QUESTIONS
Problem Identification
1.a. What are this patient’s drug therapy problems?
• Type 2 DM is uncontrolled on current drug therapy and lifestyle modifications.
• Hypertension is uncontrolled on the current dose of an ACE
inhibitor.
• Dyslipidemia is uncontrolled on the current moderateintensity statin therapy.
• Bipolar condition seems to be controlled on the current drug
regimen (although it should be noted that the patient’s atypical
antipsychotic medication may have an impact on her glycemic
control).
• Obesity is uncontrolled and contributes to the instability of the
patient’s diabetes, hypertension, and dyslipidemia.
1.b.What findings indicate poorly controlled diabetes in this
patient?
• Self-monitored blood glucose levels range from 215 to
280 mg/dL.
• Self-monitored fasting blood glucose levels average 200 mg/dL.
• A random blood glucose is 243 mg/dL.
• The A1C is 10.0%.
• Signs and symptoms of hyperglycemia in this patient include
polydipsia, polyuria, and nocturia.
Desired Outcome
2.a. What are the goals of treatment for type 2 diabetes in this
patient?
• Control of blood glucose levels as close to normal as possible.
• Preprandial plasma glucose: 80–130 mg/dL.
• Short-term goals for diabetes are to prevent and relieve acute
complications.
• Long-term goals for diabetes are to prevent and maintain any
microvascular and macrovascular complications and improve
patient’s quality of life.
• The goals for dyslipidemia are HDL ≥40 mg/dL for men,
HDL ≥50 mg/dL for women, and triglycerides <150 mg/dL.1,2
Treatment is now based on the 10-year atherosclerotic cardiovascular disease (ASCVD) risk or the presence of ASCVD
risk factor(s) rather than the patient’s LDL goal. ASCVD risk
factors include LDL cholesterol >100 mg/dL (2.6 mmol/L),
high blood pressure, smoking, albuminuria, and family history
of premature ASCVD.
• Lower blood pressure to a goal of <140/90 mm Hg.1,3 A lower
blood pressure goal of <130/80 mm Hg may be appropriate if it
can be achieved without treatment burden.1,3
• The long-term goals for treating hypertension, dyslipidemia,
and obesity are to reduce the risk factors for developing
cardiovascular disease, thereby preventing the development
or progression of the complications of target organ disease
(including nephropathy and retinopathy in the case of both
diabetes and hypertension). Management and goals of therapy
are determined in part by the stage or severity of the disease
and the presence of various risk factors.
• Initial goal for obesity is a 10% weight reduction form baseline
within a 6-month time period. The rate of weight loss should be
no more than 1–2 lbs/week to maintain the loss.4
2.b.What individual patient characteristics should be considered in determining the treatment goals?
• Setting individual goals should be based on the patient’s ability
to understand and carry out the treatment regimen, her risk for
severe hypoglycemia, and other factors, such as age and comorbidities, that may increase risks or decrease benefits.
• Although the Zyprexa could have precipitated the diabetes
and caused weight gain, this drug plays an important role in
the treatment of the bipolar disorder.5 Therefore, the goal is to
achieve the goals of the other comorbidities while maintaining
the drug regimen for this patient’s seemingly well-controlled
bipolar disorder.
Therapeutic Alternatives
3.a.What nonpharmacologic interventions should be recommended for this patient’s drug therapy problems?
Diabetes mellitus:
• Have the patient begin testing her blood glucose at least twice
a day (preferably one fasting, one preprandial, and one 2-hour
postprandial per day) and recording her results in a blood glucose diary. Have the patient test her blood glucose at different
times of the day to get a more complete picture of her blood
glucose levels.
• Improve lifestyle modifications and exercise.
• Reduce or avoid alcohol consumption.
• Encourage weight reduction with diet and exercise.
• Refer to a dietitian for medical nutrition therapy.
• Receive diabetes self-management education according to
national standards.
Copyright © 2017 by McGraw-Hill Education. All rights reserved.
Type 2 Diabetes Mellitus: Existing Disease
Sharon B. S. Gatewood, PharmD, FAPhA
• A1C <7%.1
CHAPTER 85
85
• Peak postprandial plasma glucose: <180 mg/dL (measurements
should be made 1–2 hours after the beginning of the meal).
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Hypertension:
SECTION 8
• Decrease salt intake to <1.5 g of sodium per day.
1
• Recommend the DASH diet—a diet rich in vegetables, low-fat
dairy products, and fruits, along with a dietary reduction in
total and saturated fat intake.
• Work with dietitian to maintain adequate potassium, calcium,
and magnesium.
• Encourage weight reduction with diet and exercise.
Endocrinologic Disorders
Dyslipidemia:
• Work with dietitian to incorporate the therapeutic lifestyle
change (TLC) approach, which includes keeping saturated
fats to <7% of total calorie intake and cholesterol intake to
<200 mg/day, incorporating 2 g/day of plant stanols/sterols
and increasing fiber to 10–25 g/day.1,2 This should be combined
with a decreased total daily caloric intake to help decrease
weight.
• Recommendations should focus on reducing saturated fats,
cholesterol, and trans unsaturated fat intake. Increase omega-3
fatty acids and viscous fiber, such as oats, legumes, and citrus,
in diet.1
• Encourage weight reduction with diet and exercise. An exercise
plan for this patient should be cleared with her physician prior
to starting.
Obesity:
• Initiate a low-calorie diet (LCD) that includes 800–1500 kcal/
day under the guidance of a dietitian.5 The LCD should employ
the principles of the TLC for helping to control cholesterol.
• Exercise initially for 30–45 minutes at least three times per
week including some type of cardio activity (eg, rapid walking).
Maintenance exercise should consist of 30 minutes or more of
moderate activity at least 5 days of the week to maintain weight
loss. An exercise plan for this patient should be cleared with
her physician prior to starting.4
Bipolar disorder:
• Continue psychotherapy.
• Initiate an exercise program that will help to relieve stress and
depression. An exercise plan for this patient should be cleared
with her physician prior to starting.
• Encourage alcohol avoidance. If the patient continues to consume alcohol, encourage her to have no more than one to two
drinks per week.
3.b. What pharmacologic interventions could be considered for
this patient’s drug therapy problems?
Diabetes mellitus:
• Metformin plus insulin is a reasonable option. Metformin is
very effective in obese patients, who are starting oral agents, is
considered first-line therapy along with lifestyle modifications,
and should be continued in this patient with insulin therapy.
Metformin improves glycemic control by decreasing hepatic
glucose production, thereby decreasing blood glucose levels.
It decreases intestinal absorption of glucose and improves
peripheral glucose uptake and utilization, thereby improving
insulin sensitivity and decreasing the risk of hypoglycemia
(relative to secretagogues, such as sulfonylureas, or insulin
therapy) and may aid in weight loss. When used alone, metformin decreases the fasting blood glucose by about 60–70 mg/dL
and A1C by 1.5–2%.6 Metformin can also have a positive effect
on LDL, TG, and weight.
Copyright © 2017 by McGraw-Hill Education. All rights reserved.
Insulin therapy is being initiated earlier in the management
of type 2 diabetes to be more aggressive in obtaining goals for
blood glucose and A1C. Patients may be started on a “bedtime
intermediate-acting insulin or a morning long-acting insulin (can initiate with 10 units or 0.1–0.2 units/kg per day).”7
Depending on the pattern of the blood glucose levels, an
intermediate- or long-acting basal insulin and rapid- or shortacting insulin may be necessary to treat the patient to target.
Any combination of these insulins may be necessary depending on the patient’s blood glucose trends, work, and meal
schedule. Insulin is the most effective diabetes medication to
lower blood glucose, with no maximum dose or effect, and
will help the patient to reach her goal A1C.7 Insulin glargine
is considered a peakless insulin with a duration of action from
20 to 24 hours and may be an appropriate addition.
• Metformin plus glucagon-like-peptide-1 (GLP-1) analog therapy
(albiglutide, dulaglutide, exenatide, or liraglutide) is a reasonable option. These injectable medications have been approved
for use as monotherapy or as combination therapy for the
management of type 2 diabetes. Drugs in this class are analogs
of incretin (GLP-1), substance which increase the secretion of
insulin, increase β-cell growth, slow gastric emptying, and possibly decrease food intake. These medications can also be used
in combination with thiazolidinediones and sulfonylureas.
• Metformin plus sulfonylurea (eg, glyburide) dual combination
therapy may result in improved glycemic control initially and
is relatively cost effective, but the magnitude of benefit over
monotherapy with metformin may be small. Maximum effective doses of sulfonylureas are lower than previously assumed,
and continued exposure to high concentrations may downregulate β-cell sensitivity.6 It would also increase the risk of
adverse effects including hypoglycemia, hyperinsulinemia, and
weight gain. However, this combination would be an option if
the patient was not willing to start insulin therapy.
• Metformin plus thiazolidinedione (rosiglitazone or pioglitazone) is an option. Thiazolidinediones represent a therapeutic approach for this patient that addresses insulin resistance
as its primary mechanism of action by insulin sensitivity of
muscle and adipose tissue.6 This regimen may improve glycemic control through improved glucose utilization without
increasing (and by possibly decreasing) insulin requirements.
However, these medications are costly and require intensive
monitoring of liver enzymes prior to and during therapy.
Thiazolidinediones will not achieve the necessary lowering of
the patient’s A1C to goal. In addition, thiazolidinediones commonly cause weight gain, and for this reason, it may be prudent
to avoid their use in this patient at this time.
• Metformin plus sulfonylurea plus thiazolidinedione (triple-drug
therapy) is becoming a common strategy to treat type 2 DM.
However, this approach is more expensive than the other
options available for this patient. It could be considered if the
patient does not respond to changes in other double combination oral therapy and is resistant to starting insulin or GLP-1
analog therapy. If the triple-drug therapy is needed, a combination drug can be used to decrease the total number of drugs
that the patient is taking.
• Metformin plus dipeptidyl peptidase-4 (DPP-4) inhibitor (sitagliptin, saxagliptin, linagliptin, or alogliptin) has a complimentary effect when taken together. Sitagliptin, saxagliptin,
linagliptin, and alogliptin have been approved as monotherapy
or for use in combination therapy (eg, with metformin, thiazolidinediones, or sulfonylureas). In combination with either
metformin or a thiazolidinedione, the three key defects can
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• Metformin plus an α-glucosidase inhibitor (acarbose or miglitol). α-Glucosidase inhibitors are unlikely to produce a satisfactory response because they decrease postprandial blood
glucose levels with minimal effect on fasting levels. These
agents, when used in combination with other diabetes medications, are generally unacceptable due to additive GI adverse
effects, poor adherence prospects, and additional costs.
• Metformin plus a meglitinide derivative (repaglinide or nateglinide) is a reasonable option. Meglitinide derivatives are
nonsulfonylureas that stimulate phase I insulin secretion.
They have a rapid onset and short duration of action, which
allows for flexible adjustable dosing given two, three, or four
times a day, with each meal. Repaglinide is approved for use
as monotherapy or in combination with metformin. Its rapid
elimination may lessen the risks of prolonged hypoglycemia
and downregulation of β-cell sensitivity.6 Adjustable dosing
schedules may allow for more flexible and individualized drug
therapy management plans for patients on oral agents. Nateglinide is a phenylalanine derivative that works similarly but
may be more dependent on and responsive to glucose levels.
Patients inadequately controlled with glyburide or other insulin secretagogues should not be switched to these agents, nor
should they be added to the regimen.
• If the A1C target is not achieved after about 3 months of dual
therapy, proceed to three drug combination.1
• BIDS therapy (bedtime insulin/daytime sulfonylurea) has been
increasingly successful when initiated before titration to maximum doses of sulfonylureas and while there is still sufficient
β-cell function intact. It provides for a period of interim
insulin use with only one daily injection. Bedtime administration of insulin enhances the suppression of nocturnal hepatic
glucose production that occurs in the fasting state. It does pose
increased risks for weight gain, hypoglycemia, and hyperinsulinemia. Increased frequency of self-monitoring of blood glucose (SMBG) and patient acceptance may be limiting factors.
✓Though not an approved indication, an interesting regimen
to consider might be bedtime insulin to suppress fasting
glucose levels plus nateglinide to stimulate phase 1 insulin
secretion and control postprandial glucose levels.
Hypertension:
• Increase dose of lisinopril by 5 mg/day in 1- to 2-week intervals
up to a maximum of 40 mg/day given as a single daily dose or
divided dose. In patients with type 2 diabetes, hypertension,
and microalbuminuria, ACE inhibitors have been shown to
delay the progression to macroalbuminuria and nephropathy.1,3
An angiotensin receptor blocker (ARB) may be used in place
of the ACE inhibitor if the patient is unable to tolerate an ACE
inhibitor due to cough, for example.
• Addition of a thiazide diuretic such as hydrochlorothiazide
12.5 mg/day. Combination therapy at low doses should minimize the potential adverse effects of either agent when used
alone at higher doses. A low dose of hydrochlorothiazide will
have minimal adverse effects on glycemic control. Many studies have shown a reduction in morbidity and mortality with the
use of diuretics. The current lisinopril dose should be sufficient
to delay the progression to macroalbuminuria. If a patient with
diabetes needs combination therapy to control blood pressure,
the combination of an ACE inhibitor and thiazide diuretic is
an option. In addition, this would be the most cost-effective
option and can be made available in a one pill for once a day
dosing.
• Addition of a calcium channel blocker such as amlodipine
5 mg/day. When compared to the combination of an ACE
inhibitor and a thiazide diuretic, adding a dihydropyridine
calcium channel blocker to an ACE inhibitor has been shown
to be similarly effective in reducing blood pressure but more
effective in reducing the risk for cardiovascular events (myocardial infarction, MI) in hypertensive patients at risk for MI,
including those with diabetes.8 Nondihydropyridine calcium
channel blockers may provide renal protective benefit in the
setting of diabetes. In addition, a nondihydropyridine could be
considered as an alternative to an ACE inhibitor when there
is an intolerance due to angioedema or renal artery stenosis.9
Dyslipidemia:
• This patient’s calculated 10-year ASCVD risk is 3.9%, and her
lifetime ASCVD risk 50%. All patients with diabetes ≥40 years,
should be maintained on moderate-intensity statin. Additionally, the patient’s triglycerides are elevated (225 mg/dL),
Copyright © 2017 by McGraw-Hill Education. All rights reserved.
Type 2 Diabetes Mellitus: Existing Disease
• Metformin plus sodium-glucose cotransporter 2 (SGLT2) inhibitor (canagliflozin, dapagliflozin, and empagliflozin) is an
option. Inhibition of SGLT2, located in the proximal renal
tubules, prevents reabsorption of glucose from the tubular
lumen, and leads to increased urinary excretion of glucose.
This novel mechanism of action does not involve insulin
secretion or resistance as a target for diabetes therapy. Weight
loss, potentially due to increased excretion of glucose and
associated calorie loss, has been seen with use and may be an
added benefit in type 2 diabetes patients who are also overweight. SGLT2 inhibitors are taken before the first meal of the
day. Their use is contraindicated in patients with severe renal
impairment, including patients with end-stage renal disease
and those on dialysis. Due to the risk of hypotension, volume
status must be assessed and corrected, if necessary, before
starting therapy, as well as monitored throughout the course of
therapy. Monitoring of serum potassium and LDL cholesterol
levels is recommended, as they may increase due to SGLT2
inhibitor use.
• Pramlintide is a synthetic version of the natural hormone
amylin. Amylin is released from the pancreas β-cells at the
same time as insulin in response to food. It primarily affects
postprandial blood sugars by delaying gastric emptying, stops
glucagon production, and promotes satiety. It can be an adjunct
medication for type 2 diabetes patients on metformin, sulfonylureas, or insulin. It is an injectable medication which must be
given with a meal.
CHAPTER 85
be addressed: insulin resistance, α-cell dysfunction, and β-cell
dysfunction. The DPP-4 inhibitors work by inhibiting the
DPP-4 enzyme which is responsible for the breakdown of
GLP-1. GLP-1 functions in the body include: promoting satiety
and reducing appetite, slowing gastric emptying, decreasing
postprandial glucagon secretion by its action in the pancreatic
α-cells (which further reduces hepatic glucose output) and
increasing glucose-dependent insulin secretion by its action in
the pancreatic β-cells. Kidney function must be assessed before
starting sitagliptin, saxagliptin, and alogliptin and, if necessary,
a required dose adjustment before initiation. Pancreatitis is
a possible concern with each of DPP-4 inhibitors. Reports of
hepatotoxicity have also been associated with DPP-4 inhibitors,
as these agents are major substrates for the CYP3A4 enzyme.
Thus, possible drug–drug interactions should be assessed
before use. Hypersensitivity reactions are also possible with
DPP-4 inhibitors. Each of the DPP-4 inhibitors is available in a
combination product with metformin if this option is chosen
to decrease the total number of pills taken by the patient.
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SECTION 8
while her HDL level is good (58 mg/dL). Treatment goals are
triglycerides <150 mg/dL and HDL above 50 mg/dL. Based on
her additional risk factors, a high-intensity statin could be considered appropriate treatment.1,2 The primary goal for a patient
with diabetes is to minimize the ASCVD risk and control or
reduce the number of ASCVD risk factors. Treatment should
not be initiated for triglycerides unless hypertriglyceridemia
(eg, >500 mg/dL) exists.1
• Options for the treatment of this patient’s dyslipidemia include:
Endocrinologic Disorders
✓Do not adjust pharmacologic therapy for cholesterol in this
patient until diabetes is under control. Continued exercise
will help raise HDL-C, and decreasing the intake of saturated
fats will help lower triglycerides. Also as the patient’s glucose
begins to decrease, the triglycerides will follow.
✓Increase statin to a high-intensity statin. This patient currently has some additional risk factors including hypertension, LDL >100 mg/dL, and obesity. While she does
not smoke and her family history is unknown, it could be
considered to increase her statin to rosuvastatin 20–40 mg
or atorvastatin 40–80 mg as tolerated.1
• Options for the treatment dyslipidemia which should NOT be
considered for this patient include:
✓Addition of lomitapide or mipomersen. Lomitapide is a
microsomal triglyceride transfer protein inhibitor only
approved for use in patients with a clinical diagnosis of
homozygous familial hypercholesterolemia (HoFH), which
is characterized by elevation of LDL cholesterol, deposition
of LDL-derived cholesterol in tendons and arteries, and
genetic inheritance of the condition. Severe hypercholesterolemia (total cholesterol >500 mg/dL) is seen in this rare
condition. Lomitapide is used as an adjunct to other lipidlowering therapies (including LDL apheresis and other lipidlowering medications) and diet modification. Mipomersen
is an oligonucleotide inhibitor of apolipoprotein B-100 synthesis which is also only approved for use in HoFH patients
and used as an adjunct to other lipid-lowering therapies and
diet modification. Both lomitapide and mipomersen reduce
LDL, total cholesterol, apolipoprotein B, and non-HDL
cholesterol. Lomitapide is a once daily oral medication,
whereas mipomersen is a once weekly subcutaneous injection. Lomitapide and mipomersen have a risk of hepatoxicity
and are only available through restricted programs under
a Risk Evaluation and Mitigation Strategy (REMS). The
patient does not meet the criteria for use of either of these
medications.
✓Addition of Omega-3 Fatty Acids. (Epanova, Lovaza, Omtryg,
or Vascepa) Icosapent ethyl is an ethyl ester of the omega-3
fatty acid eicosapentaenoic acid (EPA), which reduces hepatic
very low-density lipoprotein triglyceride (VLDL-TG) synthesis and secretion and increased triglyceride clearance
from VLDL particles in the blood. It is indicated for use in
adult patients with hypertriglyceridemia (≥500 mg/dL) as an
adjunct to diet. The patient does not meet the criteria for use
of this medication.
✓Addition of PCSK9 Inhibitors (alirocumab and evolocumab).
These human monoclonal antibodies bind proprotein convertase subtilisin kexin type 9 (PCSK9) to stop its binding
to LDL receptors which in turn prevents the clearing of LDL
and lowers LDL levels. PCSK9 inhibitors are indicated for
the treatment of heterozygous familial hypercholesterolemia and clinical atherosclerotic cardiovascular disease. The
patient does not meet the criteria for use of this medication.
Copyright © 2017 by McGraw-Hill Education. All rights reserved.
✓Addition of fibric acid derivatives (gemfibrozil and fenofibrate) is no longer an option for patients currently on a
statin. The FDA has concluded that the cardiovascular benefit does not outweigh the risk of the combination of these
classes of medications.
✓Addition of niacin is no longer an option for patients
currently on a statin. The FDA has concluded that the
cardiovascular benefit does not outweigh the risk of the
combination of these classes of medications.
Obesity:
• Because patient has not maintained the current lifestyle modifications, they will be reinitiated. Most of the prescription
weight loss medications contain some form of stimulant which
may adversely affect blood pressure. Therefore no drug therapy
will be started for this patient at this time, because of the presence of uncontrolled hypertension.
• OTC Orlistat could be an option for weight loss for this patient.
However, it is not a practical option for this patient due to her
binge eating to self-treat her mood swings. As such, this patient
may potentially suffer from the adverse gastrointestinal effects
that are associated with this medication.
Optimal Plan
4.What pharmacotherapeutic regimen would you recommend
for each of the patient’s drug therapy problems?
Diabetes mellitus:
• This patient is currently being treated with metformin 1000 mg
BID with meals along with lifestyle modifications, which is
consistent with ADA guideline recommendations. Metformin
is the drug of choice in patients who are obese because it has
been shown to reduce weight and improve the lipid profile and
glycemic control. However, the patient has not reached their
therapeutic target (A1C <7%) on metformin monotherapy,
and an additional agent is therefore needed. The patient should
be started on 10 units insulin glargine subcutaneously daily
(either at bedtime or in the morning, as long as the time of day
is consistent) and continued on her current dose of metformin
1000 mg BID with meals. The patient should be instructed to
test fasting blood sugar daily to see if this dose is adequate to
achieve target fasting blood glucose levels (80–130 mg/dL). If
the fasting blood glucose is outside of this range, a reasonable
titration would be to increase the insulin glargine dose by an
additional 2 units every 3 days as needed to achieve the goal
fasting blood glucose.7
✓Education should be provided to the patient on the subcutaneous insulin injection technique including the patient
demonstrating a proper injection technique.
✓Education on the appropriate treatment and management of
hypoglycemic episodes should be provided.
✓Emphasis on appropriate SMBG, lifestyle modifications, and
exercise should be discussed with the patient.
Hypertension:
• Hydrochlorothiazide 12.5 mg should be added to the ACE
inhibitor, lisinopril. These two classes of drugs in combination
will have a synergistic effect on control of the hypertension.
• The ACE inhibitor will be continued at the current dosage.
Strong consideration should be given to the use of ACE inhibitors in all patients with diabetes, not only for control of hypertension and renal protection, but also for cardiovascular risk
reduction. The need for cardiovascular risk reduction is present
85-5
✓If the patient wishes to not take an additional medication,
a lisinopril/HCTZ combination product is available for a
convenient one tablet daily dosing in various strengths.
Dyslipidemia:
✓ Once the diabetes goals are achieved, the goal for the triglycerides will likely be reached.
✓A fasting lipid panel should be drawn on an individual basis
to monitor for adherence and efficacy of the statin.1
Obesity:
• Because the patient has not maintained the current lifestyle
modifications, they will be reinitiated. No drug therapy should
be started for the patient at this time, secondary to the presence
of uncontrolled hypertension.
• OTC Orlistat could be an option for weight loss for this patient.
However, it may not be well tolerated if the patient continues
her dietary habits of binge eating to self-treat her mood swings.
Bipolar disorder:
• No change will be made to the drug regimen treating the
bipolar disorder at this time. The patient’s bipolar disorder is
currently stable on the current medication regimen. Although
there is a chance that the Zyprexa may be contributing to the
diabetes progression and increased weight gain, the benefits
of this drug may outweigh the risk of losing adequate control
of the patient’s bipolar symptoms.5 The atypical antipsychotics
tend to be better tolerated by patients with fewer side effects
than the typical antipsychotics. Three atypical antipsychotics,
aripiprazole, ziprasidone, and lurasidone, have been shown
to have a lower incidence of weight gain than olanzapine if a
future change in therapy is needed.10 At this time, the typical
antipsychotics are not a good option for this patient.
Outcome Evaluation
5.What parameters should be monitored to evaluate the efficacy
and possible adverse effects associated with the optimal regimens you selected?
Diabetes mellitus:
• Efficacy monitoring:
✓Increase the frequency of SMBG to include fasting, postprandial, and bedtime measurements, and monitor for the
occurrence of signs and symptoms of hypoglycemia or
hyperglycemia until the patient’s goals are reached. Have the
patient record her results in a log book and share them with
you and her physician at every visit.
✓Follow-up with the patient in 3 days after initiation of basal
insulin therapy to assess fasting blood glucose measurements. If patient’s fasting blood glucose is elevated and not in
the target range (80–130 mg/dL), increase dose by 2 units.7
Continue dose titration and follow-up schedule until the
patient is in target fasting blood glucose range.
✓Educate patient about what to do if she becomes
hypoglycemic.
✓Measure the A1C every 3 months until stable. Then measure
twice a year for maintenance.
✓The most common adverse effects of insulin glargine are
hypoglycemia, injection site reactions, allergic reactions,
weight gain, pruritus, lipodystrophy, and rash. Counsel the
patient to make sure that she uses a proper insulin injection
technique, rotates her injection site daily, and knows the
proper treatment of a hypoglycemic episode.
✓Baseline renal and hepatic function tests should be done
prior to starting insulin therapy and then at least yearly during course of therapy.
• Adverse effect monitoring (metformin):
✓The most common adverse effects of metformin are GI in
nature (nausea, vomiting, epigastric fullness, diarrhea, or
constipation). Ask the patient if she is experiencing these
symptoms and to what extent they are occurring. Counsel
the patient to take her metformin with food. These side
effects are common within the first 2–3 weeks and then
should subside.
✓Lactic acidosis is a rare but potentially severe consequence of
metformin therapy. The drug is contraindicated in patients
with disorders that increase the risk of lactic acidosis. These
include acute heart failure, renal impairment (SCr: ≥1.5 mg/dL
in males or ≥1.4 mg/dL in females), chronic or acute metabolic acidosis, liver failure or hepatic disease, chronic or
excessive ethanol use, dehydration, and hypoxemic states
(including respiratory failure). Renal and liver function must
be monitored throughout the course of therapy.
✓Baseline renal function tests should be performed prior to
initiation of therapy and then at least yearly. Therapy should
be discontinued if serum creatinine is ≥1.5 mg/dL in men or
≥1.4 mg/dL in women.
✓Baseline liver function tests (ALT) should be performed
before initiation of therapy. Tests should also be obtained
if the patient develops nausea, vomiting, abdominal pain,
fatigue, anorexia, dark urine, or jaundice. If the ALT is
moderately elevated ALT (>1–2.5 times normal) at any time
during therapy, patients should be evaluated to determine
the cause, and more frequent monitoring should occur.
If the ALT increases to >3 times the upper limit at any time,
the test should be repeated as soon as possible. If it remains
elevated at >3 times the upper limit of normal, the drug
should be discontinued.
Hypertension:
• Efficacy monitoring:
✓Blood pressure needs to be monitored once a week until
patient reaches goal of <140/90 mm Hg.
• Adverse effect monitoring:
✓For lisinopril, monitor the patient’s blood pressure for hypotension and evaluate the patient for hypotensive symptoms
(eg, fatigue, dizziness, headache, and fainting). Ask the
patient about the presence of cough, skin rash, and taste
disturbances. Monitor serum creatinine and potassium at
baseline, approximately 1 week after initiation of therapy
or dosage titration, and then periodically. Although rare,
patients should be aware of signs and symptoms of angioedema; this may present as facial swelling (lips, and around
eyes) and swelling in the extremities (legs and arms). This is
a very serious reaction and patients should be made aware
of the severity of it and instructed on what to do if these
symptoms occur.
Copyright © 2017 by McGraw-Hill Education. All rights reserved.
Type 2 Diabetes Mellitus: Existing Disease
• Pravastatin 40 mg should be continued because it is a moderate
intensity statin, which is recommended for this patient due to
ASCVD risk.2
• Adverse effect monitoring (insulin glargine):
CHAPTER 85
in all patients with diabetes, regardless of whether hypertension exists as a comorbid problem.
85-6
SECTION 8
✓Hydrochlorothiazide can cause hypotension, fluid and electrolyte disturbances, and sensitivity to sunlight. Monitor BP
and for symptoms of hypotension, low potassium (aching
muscles and leg cramps), and gout. Serum creatinine, potassium, lipids, glucose, and uric acid levels should be measured periodically. Serum potassium and uric acid should be
measured within 2–6 weeks after initiation of therapy.
Dyslipidemia:
• Efficacy monitoring:
Endocrinologic Disorders
✓A fasting lipid panel should be drawn on an individual basis
to monitor adherence and efficacy of the statin.
• Adverse effect monitoring:
✓Monitor the risk for hepatotoxicity by checking the ALT and
AST at baseline and then again if symptoms suggestive of
hepatotoxicity exist.
✓If AST or ALT increase to >3 × upper limits of normal
(ULN), either reduce the dosage or discontinue pravastatin.
✓Educate patient on the signs and symptoms of rhabdomyolysis (eg, intense muscle pain and tea-colored urine) and
instruct the patient regarding what to do if symptoms occur.
Bipolar disorder:
• Efficacy monitoring:
✓Have patient continue with her psychotherapy and monitor
efficacy by talking with the patient when she picks up her
Zyprexa refill.
• Adverse effect monitoring:
✓Monitor the patient’s blood sugar closely since she will
remain on the Zyprexa for the bipolar disorder. The patient
should also be monitored for the following adverse effects
while taking Zyprexa: somnolence, weight gain/increased
appetite, constipation, dizziness, akathisia, asthenia, and dry
mouth. Although many of the extrapyramidal symptoms
are more common with the first-generation antipsychotics,
these adverse effects can still occur with the atypical antipsychotics and need to be monitored.
Patient Education
6.What information should be given to the patient regarding
diabetes mellitus, hypertension, dyslipidemia, bipolar disorder, obesity, and her treatment plan to increase adherence,
minimize adverse effects, and improve outcomes?
General information:
• Note: Patient education regarding diabetes mellitus should be
comprehensive and delivered over a series of visits. Determine
what the patient knows and what information other members
of the healthcare team are providing.
• Diabetes is a condition in which your body cannot properly
use glucose or sugar from digested food. It builds up in the
blood and does not get into the muscles and other organs that
need it as a source of energy. Insulin allows the glucose to
move from the blood into the muscles. In type 1 diabetes, the
pancreas does not produce any insulin, so insulin injections
are needed. In type 2 diabetes, the pancreas does not produce
enough insulin or the body cannot use the insulin it produces
properly. Many people with type 2 diabetes also need to use
insulin.
• You can control your blood glucose levels by following a treatment plan designed for you that includes meal planning to fit
your needs and preferences, regular exercise, and medication.
Copyright © 2017 by McGraw-Hill Education. All rights reserved.
• The amount of glucose in your blood depends on the amount
and types of food you eat, the timing of your meals, the amount
and timing of activity or exercise (which pulls more glucose out
of the blood for energy), and the amount and timing of your
medication. High or low blood glucose levels can result if all of
these actions are not coordinated appropriately.
• Maintaining your blood glucose levels as close to normal as
possible may prevent or delay complications such as blindness,
kidney disease, nerve damage, limb amputations, heart disease,
and strokes.
• High blood sugar (or hyperglycemia) can cause symptoms such
as increased thirst; increased hunger; and increased urination;
headaches; dry, itchy skin; more frequent infections that are
difficult to cure; nausea; fatigue; blurry vision; and numbness
or tingling in the fingers or toes. If untreated, it can lead to
coma and death.
• It is important to increase the frequency of your blood glucose
monitoring while we adjust your insulin and until you reach
your goals. A schedule of testing before and after meals, fasting,
and at bedtime should be negotiated with the patient. Would
you show me how you check your blood glucose so we can
make sure everything is accurate and still working properly?
Ideally, your fasting blood glucose should stay between 80 and
130 mg/dL, and your blood glucose 2 hours after a meal should
be <180 mg/dL.
• Check your blood glucose more often if you are sick or under
any other physical or emotional stress that could cause your
levels to elevate. Always ask for advice if any of these problems
occur and before taking any nonprescription medicines.
• You can also get low blood sugar (or hypoglycemia) due to
delayed or missed meals, increased activity or exercise, alcohol
consumption on an empty stomach, or taking too much diabetes medicine, especially insulin. The warning signs of hypoglycemia include increased heart rate, weakness, dizziness,
headache, shakiness, sweating, numbness or tingling around
the mouth, irritability, drowsiness, coldness, and unconsciousness, which can progress to seizures, coma, and death. It is
important for you to know your symptoms of a low blood
sugar in order to recognize hypoglycemia so that you can treat
it appropriately.
• When any symptoms of low blood sugar occur, check your
blood glucose, if possible. If it is low, treat it immediately with
a quick-acting source of sugar such as cup of juice or regular
soda, three to four glucose tablets, glucose gel, or 1 cup of milk.
You want to ideally ingest 15–20 g of fast-acting carbohydrates.
Check your blood glucose again in 15 minutes and repeat the
treatment if necessary; then follow with a snack if a meal is not
planned within 0.5–1 hour.
• Some people do not experience any symptoms when their
blood glucose is low. Always carry some form of quick-acting
sugar with you and wear a medical alert bracelet or necklace.
• Glucagon injections may be needed to treat low blood sugar
if you cannot swallow or if you are unconscious. A Glucagon
Emergency Kit contains a vial containing 1 mg of powder with
1 mL of liquid contained in a disposable syringe with needle.
The liquid in the syringe should be injected into the vial and
mixed. Then the entire solution should be drawn back into the
syringe and injected. Although any site can be used, injecting
into the abdomen at a 45–90° angle will work most quickly.
Glucagon may cause nausea and possibly vomiting. A response
usually occurs in 5–20 minutes and should be followed with
liquids containing sugar. Check blood glucose levels every
85-7
• Good oral hygiene is important to prevent periodontal disease.
Poor glucose control can make infections very difficult to cure.
It is important to see a dentist at least yearly.
• It is very important to control all of your risk factors for
developing complications, especially your blood pressure and
cholesterol. Your blood pressure should be maintained below
140/90 mm Hg and your LDL cholesterol below 100 mg/dL.
We will check your blood pressure and cholesterol regularly. To
help control your blood pressure and cholesterol:
✓Decrease salt intake to <1.5 g of sodium per day and
get adequate amounts of dietary potassium, calcium, and
magnesium.
✓Follow a healthy diet that limits saturated fats to <7% of
total calorie intake and cholesterol intake to <200 mg/day,
incorporating 2 g/day of plant stanols/sterols and increased
viscous (soluble fiber) 10–25 g/day.
✓Try to increase the amount of vegetables, fruit, and low fat
dairy products in your diet.
✓ Always get regular exercise, keep a healthy weight, and drink
alcohol in moderation (if at all).
✓It is important to ask for advice if any problems arise, or if
you have any questions, because it is possible to control your
diabetes if everyone works together to help you learn how to
manage it.
• You should have an annual dilated eye exam to check for eye
damage (retinopathy), a yearly urine test for microalbuminuria to check for kidney disease (nephropathy), and a yearly
foot exam to check for any signs of nerve damage (peripheral
neuropathy).
• Get an influenza shot each year, the Hepatitis B vaccine series,
and a pneumococcal 23-valent vaccine once if you have never
received one. You will need a one-time revaccination of the
pneumococcal 23-valent vaccine when you turn 65 years old.
Influenza and pneumonia are common preventable infectious diseases associated with high mortality and morbidity in
people with chronic diseases, such as diabetes.
Insulin glargine:
• Insulin glargine (also known as Lantus) is a long-acting form
of insulin to treat your diabetes. It is a once-daily subcutaneous
(under the skin) injection. It helps your body to move the sugar
in your blood into your cells for energy. This type of insulin is
what is called a basal insulin (or a background insulin) and
is made to keep a constant amount, or “peakless” amount, of
insulin in your body. This should decrease your blood sugar
levels.
• To start you will inject 10 units of insulin glargine subcutaneously once daily. Is there a time that works best for you to take
• It is possible to have low blood sugars when you are on any
kind of insulin. Signs of a low blood sugar include shakiness,
anxiousness, fast heartbeat, sweating, and confusion. It is
important that you always carry a fast-acting type of sugar,
such as glucose tablets, with you at all times.
• Keeping a blood sugar and food diary will help you and your
healthcare providers see how the insulin glargine dose is working to control your diabetes. It is important to bring your blood
sugar monitor, diaries, and medications to all of your physician
visits and visits with the pharmacist to get a better picture of
how you are doing with your diabetes care.
• Notify your physician if you have any low blood sugar reactions, as he or she may need to adjust your insulin dose.
Metformin:
• Metformin (also known as Glucophage) is a medication used
to treat your diabetes. It works by allowing your body to
become more sensitive to the insulin your body is producing
and stops your liver from releasing extra sugar. This should
decrease your blood sugar levels.
• Continue taking metformin 1000 mg in the morning and
1000 mg in the evening with food. You may experience some
stomach or intestinal side effects such as nausea, vomiting,
diarrhea, or constipation. It is best to take this medication with
food to lessen some of these symptoms. These symptoms should
subside in 2–3 weeks. If these symptoms persist longer than
3 weeks or become severe or intolerable, contact your physician.
• Your physician will want you to have blood tests done to check
your kidneys and liver every 2 months for the first year of
therapy with metformin. Let the physician know if you have
any signs of tiredness, muscle pain, difficulty breathing; they
may be signs of a severe adverse effect known as lactic acidosis.
• It is best not to drink alcohol while on metformin.
Lisinopril:
• Lisinopril (also known as Prinivil or Zestril) is a medication
used to treat high blood pressure. It works by blocking an
enzyme in the body that is necessary to produce a substance
that causes vessels to tighten, so it relaxes blood vessels. This
lowers blood pressure. Lisinopril is also useful in preventing or
delaying damage to your kidneys caused by diabetes.
• You will take one 20 mg tablet each morning.
• This medicine sometimes causes dizziness or lightheadedness,
cough, skin rash, or diarrhea.
• Notify your physician if you have any signs of facial (swelling
of lips or around the eyes) or extremity (legs or arms) swelling
and/or difficulty swallowing or breathing. This is a serious side
effect of lisinopril. If this occurs, you must discontinue the
medication and report to your physician immediately.
• It is important to stay well hydrated while taking these blood
pressure medications. If you become too dehydrated your
blood pressure may drop too low.
• Do not take any nonprescription medications, including herbal
products and dietary supplements, unless you have checked
with your physician or pharmacist.
Hydrochlorothiazide:
• Hydrochlorothiazide is a medication used to treat high blood
pressure. It causes your body to lose water and salt. You will
need to urinate more frequently, especially at first.
Copyright © 2017 by McGraw-Hill Education. All rights reserved.
Type 2 Diabetes Mellitus: Existing Disease
• It is also important to check your feet daily since simple irritations, calluses, or infections can progress quickly to ulcers and
infections that do not heal well. Apply lotion to the calluses on
your feet every day, avoiding in between your toes, and wear
socks and shoes that fit properly. If any redness or discomfort
develops, or the condition worsens, consult a podiatrist.
the insulin at the same time each day? Can you show me how
you would draw up this dose and inject the insulin?
CHAPTER 85
15 minutes and follow with a recommended quick-acting sugar
until levels rise to normal. Follow with a snack to replace the
body stores of energy to prevent repeated hypoglycemia. Check
blood glucose levels every 2–4 hours for 12–24 hours. Someone
else should be instructed on how to give this injection. If you
do not recover sufficiently, call emergency personnel. While
waiting, a second dose may be given. Always notify your physician when a severe reaction occurs.
85-8
SECTION 8
• This medicine will be used with the lisinopril. Your physician
will check your blood pressure regularly to see how effective
the combination is working for your blood pressure.
• You will take one 12.5-mg tablet each morning. Do not take
the medication at bedtime to avoid having to get up to use
the bathroom during the night. There is a possibility that this
medication may need to be increased to 25 mg in a couple of
weeks if your blood pressure is still not under control.
Endocrinologic Disorders
• Hydrochlorothiazide may cause your skin to be more sensitive
to sunlight or ultraviolet light than it is normally. Exposure to
sunlight may cause skin rash, itching, redness, or other skin
discoloration. Apply a sunblock with at least an SPF 15 and
wear protective clothing, including a hat.
• It is very important that you have blood tests prior to starting
your medication and then periodically. Hydrochlorothiazide
may cause you to lose potassium in the urine. Your healthcare
provider may have you take a potassium supplement or you
may be asked to eat more food with potassium. Do not change
your diet without the advice of your healthcare provider. The
following foods contain high amounts of potassium: bananas,
coconuts, peaches, orange juice, dates, figs, and apricots. If
you experience muscle pain, weakness, or cramps, notify your
physician.
Pravastatin:
• The physician will check your lipid panel periodically to assess
for effectiveness of your medication.
• If you notice any unusual muscle aches once this medication has been started you need to contact your physician
immediately.
• This medication should be taken once a day, preferably at
bedtime because cholesterol that is made by the body is mainly
produced at night.
■■ FOLLOW-UP QUESTIONS
1.What alternative therapies might be appropriate if the initial
plan for diabetes treatment fails?
• The patient is on the recommended daily dose of metformin
and has started on basal insulin therapy with insulin glargine.
According to the ADA guidelines, the most effective approach
would be to intensify insulin therapy.7 The patient should be
testing her blood glucose and recording the results in her blood
glucose diary. The insulin glargine dose should be adjusted
approximately every 3 days until the fasting blood glucose level
falls into the target range consistently. If the patient is still not
Copyright © 2017 by McGraw-Hill Education. All rights reserved.
her target A1C, her blood glucose pattern should be evaluated
to see if she experiences high postprandial blood glucose numbers at certain times during the day. Prandial insulin may need
to be added to the patient’s drug regimen. For example, if the
patient consistently has high blood glucose results after dinner, a meal-time rapid-acting insulin dose with dinner should
be added. Patient-specific factors must be addressed. Other
approaches, such as addition of a glucagon-like-peptide-1 analog, are a possiblity.1 Lifestyle modifications, such as diet and
exercise, should be evaluated for areas of improvement and are
part of any diabetes treatment regimen.
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