Delay in Intensified Therapy Common After Metformin Failure

Miriam E Tucker

August 19, 2016

A delay in intensification of treatment after metformin failure is common in newly diagnosed type 2 diabetes and often hinders achievement of glycemic targets, suggests a new study.

"To obtain glycemic control, clinicians and patients need to escalate the therapeutic interventions earlier in the disease course and in a timelier manner," write Kevin M Pantalone, DO, an endocrinologist at the Cleveland Clinic, Ohio, and colleagues in their report published online August 12, 2016 in Diabetes Care

The most recent guidelines from the American Association of Clinical Endocrinologists (AACE) call for aggressive intensification of glucose-lowering therapy if individualized HbA1c goals aren't met after 3 months of metformin monotherapy. By contrast, in this study, the median time to intervention was 14 months, and delay to intensification was associated with a lack of achieving target HbA1c levels.

"The results of this study would seem to provide support for the…[AACE] guidelines," Dr Pantalone and colleagues note.

The study included 5239 patients with newly diagnosed type 2 diabetes who had been treated with metformin monotherapy for at least 3 months from 2005 to 2013. At that point, their mean HbA1c was 6.4%. However, 22% still had HbA1c levels above 7%, 13% above 7.5%, and 8% above 8%.

The percentages of patients in each of those three groups who did not receive an intervention within 6 months of the elevated HbA1c — defined as experiencing "clinical inertia" — were 38% for HbA1c above 7%, 31% for above 7.5%, and 28% of those above 8%.

After adjustments for confounders, patients who underwent intervention within 6 months were more likely to meet their target HbA1c levels compared with those who underwent later or no intervention (initial/baseline HbA1c > 7%; hazard ratio [HR], 0.57; P = .001; initial/baseline HbA1c > 7.5%; HR, 0.25; P = .01; initial/baseline HbA1c > 8%; HR, 0.25; P = .04).

Compared with the 62% for whom there was an intervention within 6 months, the 38% who experienced clinical inertia with HbA1c greater than 7% were slightly older: 56.0 vs 54.2 years (P = .038).

In a review of 20 randomly selected patients for whom intensification had been delayed, the inertia had been patient-driven in 11 cases and physician-driven in the other nine. With the patients, every instance "demonstrated multiple noncompliance behaviors, including missed appointments (clinical, laboratory, or nutrition consultations) and nonadherence to treatment regimens (medications, diet, or exercise)," the group writes.

On the other hand, the instances of physician inertia "were simply related to the physician's failure to intensify therapy as indicated to address an HbA1c elevation."

The study was funded by Merck Sharp & Dohme. Dr Pantalone reports receiving research funding from Novo Nordisk and Merck; receiving consulting fees from Sanofi, Novo Nordisk, Eli Lilly, and Merck; and receiving honoraria from Eli Lilly, Merck, AstraZeneca, Bristol-Myers Squibb, Sanofi, and Novo Nordisk for speaking/educational activities within the past 36 months. Disclosures for the coauthors are listed in the article.

Diabetes Care. Published online August 12, 2016. Abstract

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