CASE STUDY
PATIENT WITH NEW-ONSET TYPE 2 DIABETES MELLITUS
Stephen N. Davis, MD, FRCP
BACKGROUND
Patient AC presents with increasing fatigue, frequent urination, and excessive thirst. Her fasting
blood glucose (FBG) level is 250 g/dL, glycosylated
hemoglobin (A1c) is 9.6%, blood pressure (BP) is
145/88 mm Hg, and low-density lipoprotein cholesterol (LDL-C) is 187 mg/dL. AC is 53 and
weighs 180 lbs; her body mass index is 31.9. She
is a 43-year-old African American divorced administrative assistant who denies alcohol or tobacco use
and leads a fairly sedentary lifestyle. The patient
had gestational diabetes with her second and third
pregnancies. Diabetes mellitus (DM) was present in
her mother and maternal grandmother. Her father
died suddenly of a myocardial infarction at age 49,
and her mother died of a massive stroke at age 76.
COURSE OF THERAPY
AC was initially encouraged to take part in lifestyle
interventions and was given patient education about
the disease, its treatment, and complications. Because
lifestyle interventions alone rarely achieve or maintain
metabolic goals, AC also was started on metformin 500
mg twice a day because of its favorable effects on
weight loss and dyslipidemia. After 3 months, the
patient returned to the clinic with improved glycemic
control (FBG is 160 mg/dL, A1c is 8.6%), but no significant change in weight, lipid profile, or BP. At this
time, she was given lisinopril 20 mg/day for hypertension and simvastatin 40 mg/day for hyperlipidemia.
She was told to continue her current metformin regimen and was encouraged to make more lifestyle modifications to reduce her weight. She was maintained on
her current medications for a year, with improvements
University of Tennessee Advanced Studies in Pharmacy
seen in BP and lipid profile, but increasingly poor
glycemic control (FBG in the range of 180 mg/dL200
mg/dL and A1c >8%). She admits to frequently missing doses because of her busy schedule, forgetfulness,
and occasional gastrointestinal (GI) disturbances. Her
regimen was recently changed to a newer, extendedrelease metformin 1500 mg/day and glimepiride 4
mg/day to increase adherence to medication and
improve glycemic control. After undergoing intense
counseling on the importance of compliance with her
drug therapy, AC returned to the clinic after 3 months
with acceptable BP (130 mm Hg), lipid (LDL-C 100
mg/dL), and FBG (130 mg/dL) values.
DISCUSSION
Ideally, treatment of hypertension and dyslipidemia should be initiated simultaneously with diabetes therapy to control cardiometabolic risk factors.
According to Joint National Committee 7 guidelines,
the BP goal for patients with DM is less than 130/80
mm Hg.1 Lisinopril was chosen for hypertension
because angiotensin-converting enzyme (ACE)
inhibitors reduce BP without adversely affecting glucose, insulin, and lipid levels. ACE inhibitors also have
been shown in numerous studies to favorably affect the
progression of diabetic nephropathy and, therefore,
hold a compelling indication for patients with DM
and hypertension.2 For patients, such as AC, who have
DM and 2 or more coronary heart disease risk factors
(hypertension and family history of premature coronary artery disease), the latest cholesterol guidelines
recommend targeting LDL-C less than 100 mg/dL
(potentially <70 mg/dL) and high-density lipoprotein
cholesterol greater than 45 mg/dL. Simvastatin was
chosen for hyperlipidemia because 3-hydroxy-3methyl-glutaryl-CoA reductase inhibitors are considered the most effective drugs for reducing LDL-C
concentrations and have been shown to reduce the risk
of coronary events.2 Additionally, this patients age,
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CASE STUDY
hypertension, and family history mandate the use of
aspirin 81 mg daily to further decrease coronary risk.
According to the American Diabetes Association
diagnosis and classification system, the diagnosis of DM
is made with a fasting plasma glucose (FPG) of at least
126 mg/dL (typically useful for type 2 DM) or a random plasma glucose of at least 200 mg/dL in the presence of classical symptoms (eg, polyuria, polydipsia, and
polyphagia).3 Patient characteristics typical of type 2
DM in AC include obesity (present in 80%90% of
patients), family history of DM, history of gestational
DM (increases the risk of developing overt DM), hyperglycemia with symptoms, hypertension, and hyperlipidemia. Therapeutic goals include achievement and
maintenance of glycemic control, avoidance of future
episodes of acute hyperglycemia and hypoglycemia, and
prevention of microvascular and macrovascular complications. In combination with lifestyle interventions, sulfonylureas and metformin are reasonable options for
first-line therapy, reducing FPG by 70 mg/dL and A1c
by 1.5% to 2%. Metformins beneficial effects on reducing body weight and dyslipidemia make it an especially
appealing choice for initial monotherapy in this patient.
However, metformin dosing in this patient never
reached the therapeutic target dose of 2000 mg/day,
contributing to the patients poor glycemic control over
the first year of therapy. Central obesity, as seen in AC,
has been strongly associated with insulin resistance, a
defect that is reduced with metformin. Sulfonylureas
primarily augment pancreatic insulin release and are
preferred in lean patients who are more likely to have a
significant pancreatic insulin deficiency defect.
Because AC failed to maintain glycemic goals with
metformin monotherapy, combination therapy was
instituted. Simply switching to a different oral agent
provides little benefit, and a single agent will not reverse
all of the defects of DM. Successful oral combination
therapy will address different aspects of the disease and
may also delay the need for insulin therapy. Because of
ACs elevated A1c of 9.5% at diagnosis, combination
therapy could have been considered, indeed, for the initial management of this case. The combination of metformin and the sulfonylurea glimepiride was the logical
next step, because this combination produces additive
hypoglycemic effects, resulting in additional reduction
of approximately 60 mg/dL to 70 mg/dL in FPG and
1.5% to 2% in A1c. If the patient is willing to consider
subcutaneous injections, another logical addition to
metformin might have been exenatide, which would
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improve postprandial hyperglycemia and also contribute to further weight loss.
PHARMACY CONSIDERATIONS
In educating AC on DM, it is important to focus on
target (normal) ranges of blood glucose levels, using glucose monitoring devices, and recognizing symptoms of
hypoglycemia (eg, nervousness, restlessness, shakiness,
rapid pulse, sweating, hunger, unusual weakness, and
confusion). She also should be counseled on her other
comorbidities, including hypertension and hyperlipidemia. If the patient does not respond adequately to
maximum recommended doses of lisinopril (African
Americans are also less responsive to ACE inhibitors), it
would be reasonable to suggest that her physician add a
low dose of a diuretic (eg, hydrochlorothiazide 12.5
mg/day) or switch to a nondihydropyridine calcium
channel blocker. In counseling AC on drug therapy for
DM, it is important to explain to her that taking metformin with meals can help reduce the GI discomfort
that she is experiencing. Because metformin has the
potential to cause lactic acidosis, AC should be told to
contact her doctor immediately if she experiences
extreme weakness or dizziness, unusual muscle pain,
trouble breathing, or an irregular heartbeat. Severe vomiting, diarrhea, or dehydration also should be reported to
ACs physician. Although metformin usually does not
cause hypoglycemia on its own, the combination of metformin with a sulfo-nylurea may cause hypoglycemia.
Because sulfonylureas have a tendency to cause weight
gain, weight reduction techniques should be emphasized
to AC, because she is already considered obese. With this
concern in mind, glimepiride was chosen because it has
been reported to be weight neutral. In patients with
problems adhering to frequent dosing schedules, as seen
with AC, using extended-release formulations with
once-daily dosing may optimize medication compliance.
REFERENCES
1. Chobanian AV, Bakris GL, Black HR, et al. The seventh
report of the Joint National Committee on Prevention,
Detection, Evaluation, and Treatment of High Blood Pressure:
the JNC 7 report. JAMA. 2003;289:2560-2572.
2. Third Report of the Expert Panel on Detection, Evaluation,
and Treatment of High Blood Cholesterol in Adults (Adult
Treatment Panel III) Executive Summary. National Heart,
Lung, and Blood Institute National Institutes of Health; May
2001. NIH publication 01-3670.
3. American Diabetes Association. Diagnosis and classification
of diabetes mellitus. Diabetes Care. 2007;30:S42-S47.
Vol. 4, No. 6
July 2007
