Patients with diabetes often receive many other medications in addition
to their oral or injectable diabetes agents.
If confronted with a loss of glycemic control, providers should
investigate whether or not concomitant drug therapy may be contributing. This
is of particular consideration when starting a new medication or increasing
dosages. The theorized mechanisms for these interactions include decreased
peripheral insulin sensitivity, decreased insulin secretion and/or increased
This article summarizes information on a core group of medications to be
suspected in cases of decreased glycemic control.
The route of administration and the dose are factors that determine the
impact of this class on blood glucose. Lower risk is associated with inhaled
and topical formulations vs. oral formulations. The effect on blood glucose may
be dramatic and prolonged, requiring dose increases in diabetes medications to
achieve glycemic control during concomitant therapy.
These medications have been frequently reported to be associated with
significant increases in weight, diabetes (even diabetic ketoacidosis) and may
have an adverse effect on lipids. The weight gain appears to be rapid, within
the first few months of therapy, but may not plateau for as long as one year
after treatment initiation. The increase in weight is widely variable (2 to 10
kg) and is reportedly due to an increase in body fat, suggesting insulin
resistance as the mechanism.
The relative risk of hyperglycemia and weight gain varies between agents
within this class. Clozapine (Clozaril, Novartis) and olanzepine (Zyprexa, Eli
Lilly) appear to be ranked highest. Switching patients to the lowest risk
agents aripiprazole (Abilify, Otsuka America/Bristol-Myers Squibb), ziprasidone
(Geodon, Pfizer), or intermediate-risk agents risperidone (Risperdal, Janssen)
or quetiapine (Seroquel, AstraZeneca) is one option. However, there have been
case reports of diabetes and even DKA with agents thought to be lowest risk.
Providers should vigilantly monitor weight and blood glucose in all
patients started on these second-generation antipsychotics.
This agent is commonly used in patients with diabetes who are not
meeting optimal HDL targets. Its effect on blood glucose is dose dependent and
was reported more frequently when large doses (>2 to 3 g/day) were used.
When concomitant use is required, providers should use therapeutic
approaches to compensate for mild increases in blood glucose caused by this
This class has been associated with glucose and insulin dysregulation.
One theory related to fluoroquinolone-associated hyperglycemia suggests that
the fluoroquinolones directly inhibit insulin release.
An agent in this class, gatifloxacin (Tequin, Bristol-Myers Squibb)
appeared to have the highest association with hyperglycemia and DKA. The FDA
issued label changes for Tequin in 2006, with a contraindication in diabetes,
and subsequently it was withdrawn from the U.S. market.
The fluoroquinolone class is also associated with hypoglycemia,
theorized to be related to blockade of ATP-sensitive K+ channels. Careful
monitoring is required for all the fluoroquinolones in view of their shared
potential for delayed hyperglycemia, and perhaps early hypoglycemia, that may
be dose related.
The thiazide diuretics have long been known to contribute to
hyperglycemia. The effects appear to be dose dependent, and the extent of the
effect may vary between patients. When starting patients on medications in this
class, providers should inform patients to closely monitor their blood glucose
to determine if adjustments will be needed in their diabetes medications.
This class may cause either hyperglycemia or hypoglycemia, even
potentiating insulin-induced hypoglycemia. In addition, these agents may mask
the sympathetically mediated symptoms of hypoglycemia. Patients should be
forewarned of this information and closely monitor their blood sugar in the
presence of new or worsened sweating.
Sugar-free liquids include various cough and cold remedies,
treatments for various gastrointestinal disorders, and many others. Products
that contain sugar alcohols can raise glucose, especially with excessive or
regular use. Providers should encourage patients to read the ingredient list on
all over-the-counter liquids and avoid or minimize use of those containing any
type of nutritive sweetener. Patients may also bring in all their OTC and
herbal medications for a comprehensive review and to receive recommendations
about avoiding interactions with their diabetes.
Sympathomimetics consist of ingredients such as pseudoephedrine and
phenylephrine, which may increase blood glucose in a dose-dependent fashion.
These drugs can also increase blood pressure and are best avoided in the
presence of cardiovascular disease.
Providing a Safe OTC List as a proactive measure may assist
patients in the best product selection. A useful rule of thumb is to advise
patients to take the lowest dose for the shortest period of time.
Tertiary references list other medications associated with hyperglycemia
including pentamidine, exogenous thyroid hormone, oral contraceptives,
phenytoin, α-interferon and protease inhibitors.
In summary, it is imperative that patients are asked about all the
medications they are taking at the beginning of each provider visit. This will
enable us to determine if there are any actual or potential interactions
between their current medications and their diabetes control.
June Felice Johnson, BS, PharmD, FASHP, BC-ADM, is an Associate
Professor of Pharmacy Practice and the Director of Faculty & Site
Development at Drake University College of Pharmacy & Health Sciences, in
Des Moines, Iowa.
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