November 10, 2017
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Metformin as first-line therapy increasing in type 2 diabetes

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Researchers report a substantial increase in the use of metformin as first-line therapy for type 2 diabetes during the past 10 years; second-line therapy choices vary, according to findings published in Diabetes Care.

“Our findings reflect the continued glycemic risk burden in patients with type 2 diabetes,” Sanjoy K. Paul, PhD, chair in clinical epidemiology, biostatistics and health services research, department of medicine at the University of Melbourne and director of the Melbourne EpiCentre at The Royal Melbourne Hospital, told Endocrine Today. “Therapeutic inertia and its consequences remain poorly addressed in primary care systems.”

Paul and colleagues evaluated data from the U.S. Centricity Electronic Medical Records on 1,023,340 adults (mean age, 58 years; 68% white) with type 2 diabetes to determine trends in prescribing antidiabetes medications and intensification with second and third antidiabetes drugs. Follow-up was a mean 3.4 years.

The proportion of patients using metformin as a first-line therapy increased from 60% in 2005 to 77% in 2016. Use of sulfonylureas as first-line treatment decreased from 20% to 8%, and insulin use ranged from 8% to 10%. In 2005, 11% of patients were using thiazolidinediones as first-line therapy, but their use dropped to 0.7% in 2016; other drugs were used as first-line treatments in up to 3% of patients.

In patients prescribed metformin as first-line therapy, 48% initiated a second treatment at a mean HbA1c of 8.4%. Use of sulfonylureas as a second-line treatment decreased from 60% to 46%, whereas use of DPP-IV inhibitors increased from 0.4% in 2006 to 20% in 2016, and insulin use increased from 7% in 2005 to 17% in 2016. Rates of discontinuation in the first year were highest for SGLT2 inhibitors (25%), followed by TZDs (21%), GLP-1 receptor agonists (21%) and DPP-IV inhibitors (18%).

Seventy-eight percent of patients had at least 1-year of follow-up after starting a second antidiabetes medications. Fifty-two percent of patients were prescribed a third agent, and at the time of initiation, 16% stopped taking the second antidiabetes medication, whereas the rest added the drug on top of the others.

“We have observed that choice of antidiabetic drugs differs by patient characteristics. Nonetheless, pharmacological intensification for glycemic control occurs at high HbA1c levels irrespective of drug choice, contrary to the guidelines for therapeutic management in patients with type 2 diabetes,” Paul said. “We have seen that despite the effectiveness and increasing popularity of new antidiabetic drugs, sulfonylureas remain the most popular second-line therapy choice. Overall, use of sulfonylureas and insulin have not been reduced during the last decade.”

The discontinuation rates of new therapeutic classes were surprising, according to Paul.

“The higher cost of these newer drugs may be relevant and may also contribute to the fairly low rates of initiation of these drugs overall,” he said. “More studies, utilizing additional data sources, are needed to specifically test hypotheses for the differences in initiation, adherence and persistence between drug classes.” – by Amber Cox

For more information:

Sanjoy K. Paul, PhD, can be reached at sanjoy.paul@unimelb.edu.eu.

Disclosures: Paul reports he receives grants in support of investigator and investigator-initiated clinical studies from Amylin Pharmaceuticals, AstraZeneca, Hospira, Merck, Novo Nordisk, Pfizer and Sanofi. Please see the study for all other authors’ relevant financial disclosures.