Important Drug-Drug/Drug-Supplement Interactions with Type 2 Diabetes Medications

Type 2 diabetes (T2D) is an unfortunate reality for many patients who are seen in primary care settings on a regular basis. It is important to be aware of drug—drug and drug–supplement interactions with these patients.

When treating these patients for acute and chronic illnesses beyond their T2D diagnosis, clinicians should inquire about any dietary supplements and medications they may be taking. It is alarming that fewer than 40% of patients reveal their use of dietary supplements to their health care provider, when an estimated 20% to 30% of people on prescription medicine take some form of botanical supplement.¹For that reason, a complete drug and supplement inventory must be part of the patient intake process at each visit. Most clinicians use electronic medical software that will alert when such interactions are present. However, although this software helps to monitor for interactions, it can be fallible. It is important that clinicians be aware of some of the most common interactions with T2D medications and not rely solely on electronic software to flag such interactions.

The majority of patients with T2D are on some form of oral antidiabetic agent. Patients are most commonly prescribed biguanides (eg, metformin), historically followed by insulin secretagogues such as sulfonylureas (eg, glipizide) and meglitinides (eg, repaglinide). Other newer drugs now commonly seen include alpha glucosidase inhibitors (eg, acarbose), dipeptidyl peptidase-4 inhibitors (eg, sitagliptin), glucagon-like peptide receptor agonists (eg, exenatide), sodium glucose cotransporter 2 inhibitors (eg, canaglifl ozin), and thiazolidinediones.^2,3In addition to these agents, many patients with T2D are also on insulin therapy.

The most common co-morbidities in patients with T2D are hypercholesterolemia, obesity, and hypertension.²Current recommendations for standards of care of T2D include a daily aspirin (if not contraindicated), an antihypertensive agent (if needed), and a cholesterol-controlling agent (if needed).²It is important to note that even these baseline T2D treatment medications can have drug—drug interactions.

Medications that interact with antidiabetes drugs include, but are not limited to, the following categories: cardiac medications, decongestants, antibiotics, thiazides, steroids, thyroid drugs, estrogens, oral contraceptives, testosterone, seizure medications, psychiatric medications, and cholesterol medications.⁴Example interactions are listed in Table 1.⁵In addition to drugs, dietary supplements can also interact with antidiabetic medications. It is preferred that medicines be taken a few hours apart from any supplements, which could help decrease interactions.⁶

Table 1: Drug-Antidiabetes Drug Interactions³

Drug

Antidiabetes Drug

Possible Interaction

Metoprolol succinate (beta blocker)

Canagliflozin (SGLT2 inhibitor)

May alter glucose metabolism and prolong hypoglycemia and/or mask a hypoglycemic episode

Hydrochlorothiazide

(thiazide diuretic)

Exenatide (GLP-1 agonist)

May increase risk of nephrotoxicity and cause hyperglycemia

Pseudoephedrine

Acarbose (alpha glucosidase inhibitor)

May decrease hypoglycemic agent efficacy and cause hyperglycemia

Fluconazole (antifungal)

Glipizide, glimepiride, glyburide

(sulfonylureas)

May increase sulfonylurea levels, risking hypoglycemia

Sertraline (SSRI)

Glipizide (sulfonylurea)

May increase risk of SIADH, hyponatremia, and other adverse additive effects

GLP-1 = glucagon-like peptide receptor; SGLT2 = sodium glucose cotransporter 2; SIADH = syndrome of inappropriate antidiuretic hormone secretion; SSRI = selective serotonin reuptake inhibitor.*Please note: This is not a complete list.

A healthy diet containing fruits, vegetables, lean proteins, complex carbohydrates, and unsaturated fat is recommended for all patients with diabetes. However, maintaining this “perfect” diet on a daily basis can be a challenge. Dietary supplementation may compensate for some nutrient deficiencies, especially in a typical Western diet,⁷although, irrational or extreme consumption of these preparations can pose a risk to patients.⁷It is imperative that clinicians educate themselves on supplements that their patients may be taking. Most programs of study for Western-educated medical providers do not cover dietary supplementation in detail. This means that clinicians need to obtain additional information about dietary supplements and utilize key members of the health care team such as registered dieticians and certified nutritionists, for consult on dietary supplements.

Additionally, it is important to note that supplements are regulated by the FDA in a different way than OTC and prescription drugs. For example, the FDA can regulate claims or terms on labels such as “high potentcy.”⁶There are, however, reputable resources to reference when researching supplements and supplement brands. For example, the letters “USP” on a supplement label show the supplement has met voluntary standards set by the US Pharmacopeial Convention (www.usp.org) and that they dissolve in lab testing designed to mimic human gut absorption.⁶Other reputable sources for information on supplements are the Council for Responsible Nutrition (www.crnusa.org), NSF International (www.nsf.org), and Consumer Lab (www.consumerlab.com). Examples of supplement interactions are included in Table 2.⁵

Table 2: Supplements and Anti-Diabetes Drug Interactions

Supplement

Anti-Diabetes Drug

Possible Interaction

Niacin (vitamin B3)

Canagliflozin (SGLT2 inhibitor)

May cause hyperglycemia by decreasing hypoglycemic effect of canagliflozin

St. John’s Wort

Repaglinide, nateglinide

(meglitinides)

May decrease meglitinide levels, causing hyperglycemia

Fish oils

insulin

May cause hyperglycemia

Magnesium citrate

Glipizide

glimepiride,

glyburide (sulfonylurea)

Combo may increase risk of hyponatremia,

SIADH, and seizures

Ginger

All antidiabetic medications

May increase risk of hypoglycemia

SGLT2 = sodium glucose cotransporter 2; SIADH = syndrome of inappropriate antidiuretic hormone secretion.*Please note: This is not a complete list.

These examples are just the tip of the iceberg as far as the vast amount of drug—drug and drug–supplement interactions with antidiabetic drugs. Clinicians must always be mindful of these interactions and the importance of inquiring about any dietary supplements and medications patients with T2D may be taking. A more comprehensive list of drug–drug and drug–supplement interactions is available in Table 3.

Table 3: Examples of Common Diabetes Drug—Drug and Drug–Supplement Interactions³

Diabetic Class/Drug

Interacting Drug/Supplement

Type of Interaction

All antidiabetic drugs

Thiazide diuretics

Combo may increase medication or insulin requirement; thiazides can cause hyperglycemia. Monitor glucose.

Fish oil, krill oil (especially large doses)

Combo may decrease hypoglycemic agency efficacy; fish oils may cause hyperglycemia. Monitor glucose.

Ephedra, pseudoephedrine

Combo may decrease hypoglycemic agent efficacy; sympathomimetic may cause hyperglycemia. Monitor glucose.

Testosterone

May increase risk of hypoglycemia (additive effects). Monitor glucose.

Yohimbe

Combo may increase risk of hypoglycemia (mechanism unknown; yohimbe has MAOI activity). Caution advised. Monitor glucose.

Estrogens

Combo may decrease hypoglycemic agent efficacy, cause hyperglycemia (antagonistic effects). Monitor glucose.

Beta blockers (eg, metoprolol)

Combo may alter glucose metabolism, prolong hypoglycemia, or mask hypoglycemia symptoms. Monitor glucose.

Flax seed

Combo may increase risk of hypoglycemia, alter glycemic control (additive effects). Monitor glucose.

Ginger (especially with large doses)

Combo may increase risk of hypoglycemia, alter glycemic control (additive effects). Monitor glucose.

Gingko

Ginkgo may interfere with glycemic control by altering insulin secretion/metabolism. Monitor glucose.

Ginseng (American, Asian, or Siberian)

May enhance glucose-lowering effects, increase risk of hypoglycemia. Monitor glucose.

Niacin

Combo may decrease hypoglycemic agent efficacy; niacin may cause hyperglycemia (antagonistic effects). Monitor glucose.

Chromium picolinate

Combo may increase risk of hypoglycemia (synergistic effect). Monitor glucose.

Glucosamine

Combo may decrease hypoglycemic agent efficacy (glucosamine may increase insulin resistance and/or decrease insulin production). Monitor glucose.

Biguanides (eg, metformin)

Creatine

Combo may increase metformin levels, risk of lactic acidosis (renal excretion decreased by nephrotoxic agents). Monitor renal function.

Sulfonylureas (eg, glipizide)

SSRIs

Combo of SSRI and sulfonylurea may increase risk of SIADH, hyponatremia, other adverse side effects.

Fluconazole

Combo may increase sulfonylurea levels, risk of hypoglycemia (hepatic metabolism can be inhibited). Monitor glucose.

Magnesium citrate

Combo may increase risk of hyponatremia, SIADH, and seizures (additive effects, electrolyte abnormalities). Monitor sodium.

Insulin

Horse chestnut seed

Combo may increase risk of hypoglycemia (additive effects). Monitor glucose.

Licorice

Combo may increase risk of hypokalemia and sodium retention (additive toxicity). Monitor electrolytes.

All antidiabetic agents

Prednisone

Combo may decrease sulfonylurea efficacy; corticosteroids may cause hyperglycemia. Monitor glucose.

Phenytoin

Combo may decrease hypoglycemic agent efficacy; phenytoin may cause hyperglycemia. Monitor glucose.

MAOI = monoamine oxidase inhibitor; SIADH = syndrome of inappropriate antidiuretic hormone secretion; SSRI = selective serotonin reuptake inhibitor.*Please note: This is not a complete list.

Kim Moore FNP,is a certified family nurse practitioner currently practicing in the greater Minneapolis, Minnesota, area in the fields of primary care and wellness care. She is pursuing her doctorate of nursing practice degree at St. Catherine University in St. Paul, Minnesota.

References

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2. American Diabetes Association. Standards of medical care in diabetes—2015.Diabetes Care.2015;38(Suppl 1).
3. McCulloch DK. Patient information: diabetes mellitus type 2: treatment (beyond the basics). UpToDate website. www.uptodate.com/contents/diabetes-mellitus-type-2-insulin-treatment-beyond-the-basics. Updated June 24, 2015. Accessed August 31, 2015.
4. Morrell J. Oral diabetes medications. RXList website. www.rxlist.com/oral_diabetes_medications-page4/drugs-condition.htm. Accessed August 31, 2015.
5. Interaction. Epocrates [online database]. Accessed August 31, 2015.
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7. Zabłocka-Słowińska K, Dzielksa E, Gryszkin I, Grajeta H. Dietary supplementation during diabetes therapy and the potential risk of interactions.Adv Clin Exp Med.2014;2396):939-946. doi: 10.17219/acem/37348.