In adults with uncontrolled type 2 diabetes prescribed metformin or sulfonylurea monotherapy, earlier addition of a second noninsulin drug is correlated with shorter time to glycemic control, regardless of which medication is initiated as first-line therapy, according to findings from a retrospective cohort study.
“The American Diabetes Association-European Association for the Study of Diabetes treatment guidelines recommend using a stepwise approach to managing glycemic control among people with type 2 diabetes, with a review of blood glucose targets within 3 months of treatment initiation,” Urvi Desai, PhD, a manager at the Analysis Group in Boston, and colleagues wrote in the study background. “However, real-world evidence suggests that many patients with type 2 diabetes … do not receive intensified treatment for extended periods of time despite inadequate glycemic control when receiving monotherapy.”
Researchers identified from the UK Clinical Practice Research Datalink database 93,515 adults aged 18 to 79 years (mean age, 60 years; 59% men) who had been diagnosed with type 2 diabetes and started treatment with metformin or a sulfonylurea between 2000 and 2014. Participants had at least one record of HbA1c at least 7% after 3 months of metformin or sulfonylurea monotherapy. The first record was deemed the index date, with the baseline period defined as the 6 months prior to the index date. The researchers defined intensification as adding one or more noninsulin diabetes medication after the index date. Medication use was considered concomitant if the two agents’ supplies overlapped by at least 28 days and one or more prescriptions were dispensed for each after the first evidence of concomitant use. Follow-up continued for up to 7 years following treatment intensification.
Among the cohort, 85% were prescribed metformin as the first-line therapy. The median time from the index date to intensification was 30.9 months. During follow-up, treatment was intensified within 3 years for 42,815 participants. Early intensification was defined as less than 12 months (n = 23,761), intermediate was 12 to 24 months (n = 11,908) and late intensification was 24 to 36 months (n = 7,1456). Kaplan-Meier survival analyses were used to characterize the time from treatment intensification to achievement of glycemic control, defined as the first HbA1c measurement less than 7% after intensification.
Compared with intermediate or late intensifiers, early intensifiers were younger (mean age 59 years vs. 60 years vs. 58 years, respectively) and had diabetes and remained on monotherapy for a shorter time (P < .05). However, early intensifiers had a significantly higher Charlson Comorbidity Index score vs. intermediate or late intensifiers (P < .05). Early intensification patients also had a higher mean HbA1c level at index (8.8% for early intensifiers vs. 8.1% for intermediate intensifiers vs. 7.9% for late intensifiers), which decreased to 7.8% by 18 months after the index date, according to researchers.
Mean HbA1c decreased within the first 6 months following intensification for the intermediate (from 8.1% to 8%) and late intensification groups (from 7.9% to 7.7%).
The early intensification group had a median time from intensification to glycemic control of 20 months vs. 24.1 months for the intermediate group and 25.7 months for the late intensification group. An analysis adjusted for baseline differences found that compared with the early intensification group, the intermediate intensification group had a 22% lower likelihood of achieving glycemic control, and the late intensification group had a 28% lower likelihood of achieving glycemic control (P<.0001).
“The study findings suggest that despite higher HbA1c levels, several patients do not receive intensified treatment for extended periods of time,” the researchers wrote. “However, among those who received intensified treatment, earlier intensification may provide an opportunity not only to improve the likelihood of attaining desired HbA1c levels, but also to sustain these levels for somewhat longer periods of time than those achieved with delayed intensification, independent of the drug used as first-line therapy.” – by Jennifer Byrne
Disclosures: The study was funded by Bristol-Myers Squibb and AstraZeneca. Desai reports she is an employee of Analysis Group. Please see the study for all other authors’ relevant financial disclosures.