Pharmacology Consult

Drug interactions with diabetes

Which medications can worsen glycemic control?

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 gluconeogenesis.

This article summarizes information on a core group of medications to be suspected in cases of decreased glycemic control.

Corticosteroids

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.

Atypical antipsychotics

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.

June F. Johnson, BS, PharmD, FASHP, BC-ADM
June Felice Johnson

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.

Niacin

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 medication.

Fluoroquinolone antibiotics

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.

Diuretics

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.

Beta-blockers

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.

OTC products, other drugs

“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.

For more information:

  • Ann Pharmacother. 2007;41:1859-1866.
  • Can J Psychiatry. 2006;51:480-491.
  • Clin Infect Dis. 2005;41:1269-1276.
  • Can J Psychiatry. 2006;51:480-491.
  • Diabetes Care. 2004;27:596-601.
  • Tisdale JE et al. Drug-induced diseases: Prevention, detection and management. Bethesda, MD; ASHP. 2004;365-378.
  • Drug Safety. 2008;31:283-292.
  • Endocrin Metab Clin North Am. 2000;29:789-801.
  • Medical management of type 2 diabetes. ADA. Sixth Edition. 2008.
  • Pharmacotherapy. 2008;28:1198-1202.
  • The art and science of diabetes self-management education. AADE. 2006;689-703.

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 gluconeogenesis.

This article summarizes information on a core group of medications to be suspected in cases of decreased glycemic control.

Corticosteroids

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.

Atypical antipsychotics

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.

June F. Johnson, BS, PharmD, FASHP, BC-ADM
June Felice Johnson

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.

Niacin

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 medication.

Fluoroquinolone antibiotics

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.

Diuretics

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.

Beta-blockers

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.

OTC products, other drugs

“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.

For more information:

  • Ann Pharmacother. 2007;41:1859-1866.
  • Can J Psychiatry. 2006;51:480-491.
  • Clin Infect Dis. 2005;41:1269-1276.
  • Can J Psychiatry. 2006;51:480-491.
  • Diabetes Care. 2004;27:596-601.
  • Tisdale JE et al. Drug-induced diseases: Prevention, detection and management. Bethesda, MD; ASHP. 2004;365-378.
  • Drug Safety. 2008;31:283-292.
  • Endocrin Metab Clin North Am. 2000;29:789-801.
  • Medical management of type 2 diabetes. ADA. Sixth Edition. 2008.
  • Pharmacotherapy. 2008;28:1198-1202.
  • The art and science of diabetes self-management education. AADE. 2006;689-703.