Patients With T2D Taking Metformin Have Lowest Adherence

Andrew McGovern, MBBS

Patients with type 2 diabetes (T2D) that are prescribed metformin, the most commonly prescribed diabetes medication, are the least likely to subscribe to medical advice regarding their prescription—because of the adverse effects (AEs).

New data from the University of Surrey in Guildford, England, revealed that patients with T2D on metformin were the least likely to take their required dosages compared to patients with T2D on any other diabetes drug. Researchers believe adherence to the commonly used medication was found to suffer, mostly due to AEs that are associated with metformin such as diarrhea and flatulence.

"The importance of diabetes patients taking their prescribed medication cannot be underestimated,” Andy McGovern, BMBS, a doctoral clinical researcher at the University of Surrey, said in a statement. “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 [National Health Service] money so this is an important issue.”

The study analyzed data from 48 clinical studies including 25 oral therapies and 19 injectables—totaling 1.6 million patients with T2D—and found that 30% of metformin doses were not taken by the patients to which they were prescribed. Comparatively, 23% of sulfonylureas (Mean difference [MD] 1.5%; 95% CI, 6.5-14.7) and 20% of pioglitazone doses were not taken by the prescribed patients.

Dipeptidyl peptidase-4 (DPP4) inhibitors had the highest rate of adherence, with only 10% to 20% of doses not taken. DDP4 inhibitors are generally more tolerated by the body, giving researchers a hint as to AEs impact on dose adherence.

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

"Our research shows that the majority of poor adherence is related to the drug class and is not intrinsic to the patient: Whilst many people would like to adhere to there medications there is something about metformin which puts them off," McGovern said. "This is likely to be a combination of side effects and multiple daily dosing. Simply switching from Metformin to another medication class is likely to improve adherence and subsequently blood sugar control."

The research team acknowledged that if a medication required multiple doses per day, there may be an impact on adherence or tolerance for patients. The patients taking long-acting insulin analogs had better persistence than human insulins (Mean Difference [MD] 43.1 days; 95% CI, 22.0-64.2) and lower discontinuation rates than glucagon-like peptide-1 receptor agonists (Odds Ratio [OR] 1.95; 95% CI, 1.17-3.27).

McGovern urged patients to discuss their medications with their physicians, whether adherence struggles were from AEs or the frequency of dosing. “Fortunately for T2D 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,” he said.

In the UK, 3.8 million people have diabetes, with almost 90% having T2D. In the US, 30.3 million have the condition, of which 90% to 95% have T2D.

"The observational data shows that doctors continue to prescribe metformin for many years in large numbers of patients who are not really taking it. It is well known that patients can find it difficult to talk to their doctor about missing medication doses and this may partly explain these findings," McGovern said. "Openness is needed on both sides of the consultation to adequately tackle this issue; patients need to be honest about what they have been able to take and what they find difficult and doctors needs to be receptive to and non-judgemental about non-adherence. Our research suggests that switching medication classes in type 2 diabetes is one simple way to improve adherence; some medications appear much easier than others to take."

The study, “Comparison of medication adherence and persistence in type 2 diabetes: A systematic review and meta-analysis,” was published in Diabetes, Obesity and Metabolism.