Surry, UK—With all of the newer drugs on the market, pharmacists might be surprised by which diabetes medication tends to have the lowest adherence levels: metformin.

An article in the journal Diabetes, Obesity and Metabolism reveals that, based on a British study, patients prescribed metformin, the most commonly prescribed diabetes drug, are the least likely to follow their drug regimens because of side effects.

University of Surrey researchers looked at studies involving 1.6 million type 2 diabetes patients to determine patterns of medication use. Information for the article came from 48 studies, with 35 concerning oral therapies, 19 comparing injectable therapies, three including comparisons between oral and injectable therapies, and one that compared an oral to an inhaled agent.

Researchers determined that 30% of metformin doses prescribed to patients are not taken, compared to 23% of sulfonylureas and 20% for pioglitazone. On the other hand, some of the newer medication classes, such as DPP4 inhibitors, have higher rates of adherence—80% to 90%.

As for injectable medications, study authors point out that patients are twice as likely to stop taking glucagon-like peptide-1 (GLP1) receptor agonists, compared with insulin. Overall, the findings include:
• Compared with metformin, adherence was better for sulphonylureas (5 studies; mean difference [MD] 10.6%, 95% confidence interval [CI] 6.5-14.7) and thiazolidinediones (TZDs; 6 studies; MD 11.3%, 95% CI 2.7%-20.0%). 
• Adherence to TZDs was marginally better than adherence to sulphonylureas (5 studies; MD 1.5%, 95% CI 0.1-2.9). 
• Dipeptidyl peptidase-4 inhibitors had better adherence than sulphonylureas and TZDs.
• GLP1-receptor agonists had higher rates of discontinuation than long-acting analogue insulins (6 studies; OR 1.95; 95% CI 1.17-3.27). 
• Long-acting insulin analogues had better persistence than human insulins (5 studies; MD 43.1 days; 95% CI 22.0-64.2). 

Why the differences? Researchers posit that side effects might be the cause, noting that, for example, metformin commonly causes gastrointestinal symptoms such as diarrhea and flatulence, while DPP4 inhibitors tend to be better tolerated. Multiple doses a day also appeared to lower adherence rates, they said.

“The importance of diabetes patients taking their prescribed medication cannot be underestimated,” noted lead author Andy McGovern, BMBS, a clinical researcher at the University of Surrey. “A failure to do so can lead to complications in their condition including eye disease and kidney damage.”
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