Longer Diabetes Drug Regimens Increase Chance of Adverse Events

As type 2 diabetes mellitus (T2DM) patients age, the likelihood of comorbidities increases, as does the need for medications to manage them. Longer drug regimens increase the chance that patients will experience adverse drug effects or drug interactions.

These interactions can affect the pharmacokinetics or pharmacodynamics of the drugs, causing decreased medication efficacy or increased toxicity for the patient. As clinicians, awareness of major interactions is critical so they can be avoided.

The journal Therapeutic Advances in Endocrinology and Metabolism published a review discussing diabetic drug interactions; researchers conducted a literature search using numerous terms associated with drug interactions.

One strength of this review was that the authors provided two tables for quick reference. The first listed relevant herbs and their interactions with commonly prescribed antidiabetic drugs. The second lists antidiabetic drugs and commonly reported prescription medications with the mechanism and potential clinical effect and relevance.

Many of the clinically relevant drug interactions were based on the drug’s effect on specific hepatic CYP enzymes — sulfonylureas, thiazolidinediones, and meglitinides are the most susceptible to these types of interactions.

Researchers explained that metformin has a low interaction risk, but clinicians should be cautious when co-administering drugs that impair renal function.

With the exception of saxagliptin, dipeptidyl-peptidase-4 (DPP-4) inhibitors also showed a very low interaction potential. Specifically, the team saw CYP3A4 inhibitors and inducers affected saxagliptin.

On the other hand, giving DPP-4 inhibitors with drugs that affected the drug transporter P-glycoprotein might affect plasma levels. P-glycoprotein has a wide substrate spectrum; it is involved in the transport of drugs from different drug classes including antineoplastic drugs (e.g. docetaxel, etoposide, and vincristine), calcium channel blockers, calcineurin inhibitors (e.g. cyclosporine, tacrolimus), digoxin, macrolide antibiotics (e.g. clarithromycin), and protease inhibitors.

New antidiabetic drug classes, incretin mimetics, and sodium-glucose cotransporter-2 (SGLT-2) inhibitors, have a very low risk of drug interactions.

The authors suggested that further studies to determine possible interactions between sulfonylureas, meglitinides, and p-glycoprotein inhibitors as well as their clinical relevance.