October 27, 2014
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First-line metformin treatment decreased need for subsequent treatment in diabetes

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More than 40% of patients with diabetes do not start out their glucose-lowering regimen with metformin despite recommended guidelines, according to research published in the Journal of the American Medical Association Internal Medicine.

Initiating therapy with metformin was associated with reduced subsequent treatment intensification vs. other oral agents, without differences in hypoglycemia rates or other adverse clinical events, in a retrospective cohort study of insured Aetna members.

“Our findings suggest that starting therapy with metformin, in the absence of contraindications to this agent, is really the optimal strategy for patients beginning oral hypoglycemic therapy,” Niteesh K. Choudhry, MD, PhD, Executive Director, Center for Healthcare Delivery Sciences, Brigham and Women’s Hospital, Harvard Medical School, told Endocrine Today.

Niteesh Choudhry

Niteesh K. Choudhry

Choudhry and colleagues studied patients newly prescribed an oral glucose-lowering medication between July 1, 2009 and June 30, 2013 who filled a second prescription for an agent in the same class with a dosage greater than or equal to the WHO-defined daily dose within 90 days of the end of the first supply. Patients given other interim oral glucose-lowering prescriptions were excluded.

Of 15,516 patients who met the inclusion criteria, 8,964 (57.8%) started treatment with metformin, 3,570 patients (23%) with sulfonylureas, 948 patients (6.1%) with thiazolidinediones and 2,034 patients (13.1%) with DPP-IV inhibitors; the mean age across all treatment categories was 52 years and 47% of patients were women.

The researchers evaluated, separately, the time until a second oral agent or insulin was added, along with hypoglycemia, other diabetes-related emergency room visits and cardiovascular events.

Unadjusted analysis showed treatments other than metformin were associated with higher risk for adding a second oral agent only, insulin only and a second agent or insulin (P<.001 for all). A second oral medication was required by 2,198 patients (24.5%) prescribed metformin, 1,323 patients (37.1%) prescribed a sulfonylurea, 375 (39.6%) prescribed a thiazolidinedione and 736 (36.2%) prescribed a DPP-IV inhibitor (P<.001 for all).

The proportion of patients who later added insulin was lowest with prescribed metformin (5.1%), followed by DPP-4 inhibitor (5.6%), thiazolidinediones (6.2%) and sulfonylurea (9.1%).

Based on propensity score and multivariable-adjusted Cox proportional hazards models, treatment intensification risk increased when therapy was initiated with sulfonylureas (HR=1.68; 95%CI, 1.57-1.79), thiazolidinediones (HR=1.61; 95%CI, 1.43-1.80) and DPP-IV (HR=1.62; 95%CI, 1.47-1.79).

Metformin alternatives were not associated with decreased risk for hypoglycemia, emergency department visits and cardiovascular events. Use of sulfonylureas, however, appeared to be associated with an increased risk of CV events (HR=1.16; CI 95%, 1.04-1.29).

“Our results provide strong support for guidelines from the American Diabetes Association, American College of Physicians and others recommending the use of metformin as the first line agent for the treatment of diabetes,” Choudhry said.

In an accompanying commentary, Jodi B. Segal, MD, MPH, and Nisa M. Maruthur, MD, MHS, both of Johns Hopkins University School of Medicine, Baltimore, Md., called the investigation “meticulously conducted” but said it “adds modestly” to the knowledge base.

However, Segal and Maruthur noted the findings do demonstrate and area where patients and physicians could deepen treatment-related dialogue.

“Although it is true in some patients that the need to add an additional medication is due to their imperfect adherence to diet and exercise or adherence to the first prescribed drug, in many other patients it reflects the expected progression of disease and worsening insulin sensitivity and declining beta-cell function,” the authors wrote.

“Reframing the addition of medication as a necessary step for wellness and health maintenance may go a long way toward patient acceptance of intensification as an unfortunate but necessary part of good self-care,” they added. — by Allegra Tiver

For More Information: Choudhry can be reached at the Division of Pharmacoepidemiology, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, 1620 Tremont St, Ste 3030, Boston, MA 02120; email: nchoudhry@partners.org.

Disclosures: This work was supported by an unrestricted grant from CVS Health to Brigham and Women’s Hospital. One researcher reports an Institutional National Research Service Award and funding from the Ryoichi Sasakawa Fellowship Fund and the General Medicine Division at Massachusetts General Hospital.