Metformin Side Effects Result in Nonadherence for Diabetes Patients

More than one-third of metformin doses are not taken by patients with type 2 diabetes.

The type of drug prescribed may impact medication adherence for patients with type 2 diabetes (T2D). A new analysis published by Diabetes, Obesity and Metabolism suggests that patients prescribed metformin are the least likely to adhere to therapy, possibly due to side effects.

The study found that more than 1.6 million patients with T2D are not adherent to metformin therapy, which could severely impact treatment outcomes and increase the risk of adverse events. Since metformin is the most commonly prescribed diabetes drug, these findings will likely have widespread implications, according to the authors.

"The importance of diabetes patients taking their prescribed medication cannot be underestimated,” said researcher Andy McGovern, BMBS. “A failure to do so can lead to complications in their condition including eye disease and kidney damage. Medication which is not taken does no good for the patient but still costs the NHS money so this is an important issue.”

The authors analyzed adherence rates for 25 oral tablets and 19 injectable diabetes medications from 48 clinical trials and observational studies.

Overall, the study showed that patients taking metformin were the least likely to adhere to the required dosage compared with other drugs. The authors discovered that 30% of metformin doses were not taken compared with 23% of sulfonylurea doses, according the study. The analysis also showed that 20% of pioglitazone doses were not taken.

The authors noted that only 10% to 20% of DPP4 inhibitors doses were not taken by patients with T2D, which is interesting because they are the newest class of diabetes drugs.

For injectables, patients are twice as likely to stop treatment with GLP1 receptor agonists compared with insulin therapy, according to the study.

The authors hypothesize that adherence rates are related to the side effects for the different drugs. Metformin is known to cause gastrointestinal symptoms, while DPP4 inhibitors are typically tolerated better, according to the authors.

Additionally, adherence rates can be affected by medications that require multiple daily doses, according to the study.

"We have known for a long time that a lot of medication prescribed for chronic diseases never actually get taken,” Dr McGovern said. “What this latest research suggests is that patients find some of these medication classes much easier to take than others.”

Medication adherence is a multi-billion dollar per year problem and a significant challenge that pharmacists face on a daily basis. For nearly every disease state, medication nonadherence can result in significant harm.

The authors advise patients who are experiencing side effects that impact adherence to discuss these challenges with their health care providers.

"I urge anyone who is struggling to take their medication as prescribed, whether this is because of side effects or because the schedule is too complicated, to discuss this openly with their doctor or nurse,” Dr McGovern concluded. “Fortunately for type 2 diabetes we have lots of treatment options and switching to a different medication class which is easier to take could provide an easy way to improve adherence. I would also encourage doctors and nurses to actively ask their patients about medication adherence."