Trends in Timing of and Glycemia at Initiation of Second-line Type 2 Diabetes Treatment in US Adults

• Authors: Sridharan Raghavan, Eastern Colorado Health Care System; Theodore Warsavage, Eastern Colorado Health Care System; Wenhu G Liu, Eastern Colorado Health Care System; Katherine Raffle, Eastern Colorado Health Care System; Kevin Josey, Eastern Colorado Health Care System; David R Saxon, Eastern Colorado Health Care System; Lawrence Phillips, Emory University; Liron Caplan, Eastern Colorado Health Care System; Jane EB Reusch, Eastern Colorado Health Care System
• Journal Title: DIABETES CARE
• Volume: Volume 45, Number 6
• Publisher: AMER DIABETES ASSOC | 2022-06-01, Pages 1335-1345
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.2337/dc21-2492
• Subjects: Biology, Biostatistics; Health Sciences, Medicine and Surgery
• Keywords: Science & Technology; Life Sciences & Biomedicine; Endocrinology & Metabolism; HEMOGLOBIN A(1C) TARGETS; CLINICAL INERTIA; TREATMENT INTENSIFICATION; METFORMIN MONOTHERAPY; SEVERE HYPOGLYCEMIA; GUIDANCE STATEMENT; AMERICAN-COLLEGE; GOAL ATTAINMENT; GLUCOSE CONTROL; BLOOD-PRESSURE

Abstract

OBJECTIVE Therapeutic inertia threatens the potential long-term benefits of achieving early glycemic control after type 2 diabetes diagnosis. We evaluated temporal trends in second-line diabetes medication initiation among individuals initially treated with metformin. RESEARCH DESIGN AND METHODS We included data from 199,042 adults with type 2 diabetes in the U.S. Department of Veterans Affairs health care system initially treated with metformin monotherapy from 2005 to 2013. We used multivariable Cox proportional haz-ards and linear regression to estimate associations of year of metformin mono-therapy initiation with time to second-line diabetes treatment over 5 years of follow-up (primary outcome) and with hemoglobin A1c (HbA1c) at the time of sec-ond-line diabetes treatment initiation (secondary outcome). RESULTS The cumulative 5-year incidence of second-line medication initiation declined from 47% among metformin initiators in 2005 to 36% in 2013 counterparts (P < 0.0001) despite a gradual increase in mean HbA1c at the end of follow-up (from 6.94 ± 1.28% to 7.09 ± 1.42%, Ptrend < 0.0001). In comparisons with metformin monotherapy initiators in 2005, adjusted hazard ratios for 5-year initiation of sec-ond-line diabetes treatment ranged from 0.90 (95% CI 0.87, 0.92) for 2006 met-formin initiators to 0.68 (0.66, 0.70) for 2013 counterparts. Among those receiving second-line treatment within 5 years of metformin initiation, HbA1c at second-line medication initiation increased from 7.74 ± 1.66% in 2005 metformin initiators to 8.55 ± 1.92% in 2013 counterparts (Ptrend < 0.0001). CONCLUSIONS We observed progressive delays in diabetes treatment intensification consistent with therapeutic inertia. Process-of-care interventions early in the diabetes disease course may be needed to reverse adverse temporal trends in diabetes care.