Intensifying drug therapies did not help most adults with type 2 diabetes attain HbA1c goals, but the best results were seen with the addition of a GLP-1 receptor agonist, according to findings published in Diabetic Medicine.
Kevin M. Pantalone
“Therapeutic inertia is very common in clinical practice. A large part of therapeutic inertia has been described as ‘clinical inertia,’ which is defined as the failure to intensify therapy when it appears to be indicated,” Kevin M. Pantalone, DO, ECNU, FACE, director of clinical research and a staff endocrinologist in the department of endocrinology at the Cleveland Clinic, told Endocrine Today. “We hypothesized that another form of therapeutic inertia, which has not received much attention, is something we call ‘intensification inertia,’ which is choosing a form of intensification that has a very minimal chance of achieving the desired outcome.”
Pantalone and colleagues examined the electronic health records of 7,389 patients with type 2 diabetes (44.2% women) at the Cleveland Clinic from 2005 to 2016. Among this cohort, the researchers identified active diabetes medication use based on whether a medication was still present in a record 3 months after it first appeared. In addition, HbA1c levels were recorded and then used to stratify the cohort into three groups: 7% to 7.9% or 53 mmol/mol to 63 mmol/mol (n = 4,577; 44.8% women), 8% to 8.9% or 64 mmol/mol to 74 mmol/mol (n = 1,364; 45.2% women) and at least 9% or 75 mmol/mol (n = 1,448; 41.2% women).
Six months after baseline, the researchers monitored antidiabetes medication intensification and then calculated HbA1c goal attainment 12 months after that, with a goal of less than 7% or 53 mmol/mol.
No medication intensification was noted in most of the cohort (n = 4,647; 62.9%). Among the four forms of intensification, an increase in oral antidiabetes drug dose was the most prevalent (n = 1,401; 19%), followed by the addition of an oral antidiabetes drug (n = 857; 11.6%), addition of insulin (n = 371; 5%) and the addition of GLP-1 receptor agonists (n = 113; 1.5%).
Adding GLP-1 receptor agonist treatment led to the best rate of goal attainment in patients with baseline HbA1c between 7% and 7.9% or 53 mmol/mol and 63 mmol/mol (56.7%; 95% CI, 40.4-68.6), and adding insulin led to the lowest rate (33.7%; 95% CI, 21.9-43.6), even in comparison with no intensification (44.7%; 95% CI, 42.9-46.4), which ranked relatively high, according to the researchers.
“Interestingly, some people whose treatment was not intensified experienced an improvement in glycemic control, highlighting that there are probably many different underlying issues factored into HbA1c outcomes,” the researchers wrote. “Many of the people in the ‘no intensification’ group may have undergone lifestyle changes, experienced weight loss, and/or became more compliant with their existing antidiabetes therapies, factors not easily identifiable from electronic health records.”
For patients with baseline HbA1c between 8% and 8.9% or 64 mmol/mol and 74 mmol/mol, adding another oral antidiabetes drug to treatment yielded the best rate of goal attainment (31.9%; 95% CI, 25.1-38.1), with no intervention providing the worst rate (18.8%; 95% CI, 15.8-21.7). However, the researchers said goal attainment in this group was “low overall and generally similar among the different interventions.”
Patients with baseline HbA1c of 9% or more or 75 mmol/mol or more experienced the highest rate of goal attainment with the addition of GLP-1 receptor agonists (53%; 95% CI, 31.8-67.6) and the lowest with no intensification (29.5%; 95% CI, 25.8-33). This group also had a better goal attainment rate with insulin (43.5%; 95% CI, 36.4-49.8) compared with patients with HbA1c between 7% and 7.9% or 53 mmol/mol and 63 mmol/mol (33.7%; 95% CI, 21.9-43.6) and the patients with HbA1c between 8% and 8.9% or 64 mmol/mol and 74 mmol/mol (30.6%; 95% CI, 18.3-41).
“We feel that intensification inertia is an important issue in addressing therapeutic inertia. Many times clinicians do attempt to intensify therapy, but our research suggests that the actual choice of therapy/intervention is important and will influence the likelihood of HbA1c goal attainment,” Pantalone said. “Intensification inertia is separate from clinical inertia per say, and thus must be acknowledged and addressed as a part of the larger battle of reducing therapeutic inertia.” – by Phil Neuffer
Disclosures: This study was funded by Novo Nordisk. Pantalone reports he received research funding and participated as a consultant and on the speaker bureaus for Novo Nordisk and Merck. He also has served as a consultant for Eli Lilly and Sanofi, and participated in the speaker bureau of AstraZeneca. Please see the study for all other authors’ relevant financial disclosures.