Optimization of Albuminuria-Lowering Treatment in Diabetes by Crossover Rotation to Four Different Drug Classes: A Randomized Crossover Trial

• DOI: 10.2337/dc22-1699
• Publication Date: 2023-01-20T02:30:53Z
• Authors: Viktor Rotbain Cu...; Niels Jongs; Marjolein Y.A.M. ...; Emilie H. Zobel; Tine W. Hansen; Taha Sen; Gozewijn D. Laverman; Adriaan Kooy; Frederik Persson; Peter Rossing; Hiddo J.L. Heerspink
• Keywords: Linagliptin; Empagliflozin; Albuminuria; Crossover study; Telmisartan; Glipizide

OBJECTIVE Renin–angiotensin system (RAS) inhibitors decrease the urinary albumin to creatinine ratio (UACR) but are ineffective in up 40% of patients. We hypothesized that rotation through different drug classes overcomes RAS inhibitor resistance and tested this a randomized crossover trial. RESEARCH DESIGN AND METHODS assigned 26 adults with type 1 diabetes 37 2 UACR between 30 500 mg/g estimated glomerular filtration rate >45 mL/min/1.73 m2 4-week treatment periods telmisartan 80 mg, empagliflozin 10 linagliptin 5 baricitinib mg random order, separated by washout periods. Each participant was then re-exposed for 4 weeks induced individual’s largest reduction. Primary outcome difference response best-performing during confirmation period versus other three drugs. RESULTS There substantial variation drug. Telmisartan best performing 33 participants (52%), 11 (17%), 8 (13%). The individuals’ changed from baseline first confirmatory exposures mean −39.6% (95% CI −44.8, −33.8; P < 0.001) −22.4% −29.7, −12.5; 0.001), respectively. Pearson correlation exposure 0.39 (P = 0.017). change drugs +1.6% −4.3%, 8.0%; 0.593 baseline; at confirmation, 30.9% [95% 18.0, 45.3]; 0.001). CONCLUSIONS demonstrated large reproducible participants’ responses UACR-lowering classes. These data support systematic overcome therapy inhibition.