Drug Interactions of Concern for Diabetics

Patients with diabetes have a higher pill burden than the general population, so pharmacists should pay particular attention to potential drug interactions with antidiabetic agents.

Drug interactions may decrease medication efficacy or increase toxicity, and greater pill burden challenges adherence and adds to adverse effects.

Past research has shown that the benefits of carefully selected cardiovascular medications outweigh their risks. In addition, pharmacists should know the following facts:

• Sulfonylureas, thiazolidinediones, meglitinides, and dipeptidyl-peptidase-4 inhibitors (DDP-4s) are most susceptible to interactions.
• Glucagon-like peptide-1 (GLP-1) agonists and sodium-glucose transport protein (SGLT-2) inhibitors are least affected by drug interactions.
• Clinicians should consider altered absorption and transporter action, herbal supplements, and cytochrome (CYP) P450 interactions when selecting medications for patients with diabetes.

A team of researchers recently addressed the pharmacodynamic and pharmacokinetic interactions of antidiabetic drugs in a new study published in the April 2016 issue of Therapeutic Advances in Endocrinology and Metabolism.

The study authors conducted a literature review using the terms drug interactions, diabetes mellitus, type 2/drug therapy, humans, and hypoglycemic agents/adverse effects. They also created a summary document that reminded pharmacists about the likelihood of drug interactions concisely and thoroughly.

Here were some of their significant findings:

• Sulfonylurea-induced hypoglycemia is worsened by co-administration with azole antifungals, clarithromycin, verapamil, angiotensin-converting enzyme (ACE) inhibitors, DPP-4s, and GLP-1 agonists.
• Metformin toxicity is more likely with anticholinergics because of increased absorption and nephrotoxic agents (eg, iodinated contrast media).
• Thiazolidinedione toxicity is heightened by CYP P450 2C8 inhibitors (eg, ketoconazole, gemfibrozil, rifampicin, fluvoxamine, and trimethoprim).
• Saxagliptin concentration is affected by CYP3A4 inhibitors and inducers, and ACE inhibitors increase the risk of bradykinin-induced angioedema.
• Ginseng induces CYP3A4 (decreasing glibenclamide, pioglitazone, meglitinides, sitagliptin, and saxagliptin concentrations) and stimulates insulin secretion.
• St. John’s wort induces CYP3A4, 1A2, 2D6, and 2E1 (decreasing sulfonylureas, thiazolidinediones, meglitinides, and DPP-4 inhibitors) and induces p-glycoprotein pumps.
• Sulfonylureas, thiazolidinediones, and meglitinides are affected by hepatic enzyme interactions, metformin toxicity is mediated by nephrotoxicity, and dipeptidyl-peptidase-4 inhibitors are less affected by hepatic enzymes.