Abstract
Despite mounting clinical trial evidence to guide second-line diabetes treatment, clinical inertia could be a persistent barrier to improved care. We analyzed secular trends in second-line diabetes prescribing and timing of intensification in the largest integrated healthcare system in the US. We studied 93,317 Veterans in VA primary care with type 2 diabetes incidence and initial metformin monotherapy from 2004-2015 who were subsequently newly started on add-on therapy from 2010-2015 with a sulfonylurea (SU, n=78,924), insulin (INS, n=10,251), thiazolidinedione (TZD, n=737), or dipeptidyl peptidase 4 inhibitor (DPP4i, n=3405). We used linear and logistic regression to analyze temporal trends of second-line drug choice, of hemoglobin A1c (HbA1c) at metformin initiation and at initiation of add-on therapy, and of the time to initiating second-line therapy. Over the 6 years, SU use declined (86 to 78%, p=0.003), and INS (9 to 14%, p<0.001) and DPP4i (1.8 to 7.2%, p=0.02) use increased. In the full sample, mean HbA1c remained 7.6% at metformin initiation from 2010-2015 (p=0.2 for trend), but time to add a second drug rose (2.6 to 3.7 years) as did HbA1c at the time of add-on therapy (7.8 to 8.1%) (both p<0.001). Mean HbA1c at initiation of add-on therapy was higher in SU (7.9%) and INS (8.9%) users than in TZD (7.1%) and DPP4i (7.2%) users (p<0.001 for difference between groups). HbA1c at initiation of add-on therapy increased from 2010-2015 among SU (7.8 to 8.0%, p<0.001), INS (8.7 to 8.9%, p<0.001), and DPP4i users (6.8 to 7.4%, p<0.001). The time to treatment intensification increased from 2010 to 2015 for users of each medication class (2.5 to 3.7 years for SU; 2.5 to 3.5 years for INS; 2.9 to 4.0 years for TZD; 3.1 to 4.1 years for DPP4i; all p<0.001). Conclusions: Inertia in diabetes treatment intensification may be worsening in real-world care potentially blunting the impact of accumulating clinical trial evidence to guide optimal second-line diabetes treatment. Disclosure S. Raghavan: None. L. S. Phillips: Other Relationship; Self; Diasyst Inc., Research Support; Self; AbbVie Inc., Eli Lilly and Company, GlaxoSmithKline plc., Janssen Pharmaceuticals, Inc., Kowa Pharmaceuticals America, Inc., Novartis Pharmaceuticals Corporation, Novo Nordisk Pharma Ltd., Pfizer Inc., Sanofi-Aventis. L. Caplan: None. J. E. Reusch: Advisory Panel; Self; Medtronic. Funding U.S. Department of Veterans Affairs (IK2-CX001907-01)
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