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

Autor:	Curovic VR; 1Steno Diabetes Center Copenhagen, Herlev, Denmark., Jongs N; 2Department of Clinical Pharmacy and Pharmacology, University of Groningen, Groningen, the Netherlands., Kroonen MYAM; 2Department of Clinical Pharmacy and Pharmacology, University of Groningen, Groningen, the Netherlands., Zobel EH; 1Steno Diabetes Center Copenhagen, Herlev, Denmark., Hansen TW; 1Steno Diabetes Center Copenhagen, Herlev, Denmark., Sen T; 2Department of Clinical Pharmacy and Pharmacology, University of Groningen, Groningen, the Netherlands., Laverman GD; 3ZiekenhuisGroep Twente, Almelo, the Netherlands., Kooy A; 4Bethesda Diabetes Research Center, Hoogeveen, the Netherlands.; 5Department of Internal Medicine, University of Groningen, Groningen, the Netherlands., Persson F; 1Steno Diabetes Center Copenhagen, Herlev, Denmark., Rossing P; 1Steno Diabetes Center Copenhagen, Herlev, Denmark.; 6Department of Clinical Medicine, University of Copenhagen, Copenhagen Denmark., Heerspink HJL; 2Department of Clinical Pharmacy and Pharmacology, University of Groningen, Groningen, the Netherlands.
Jazyk:	angličtina
Zdroj:	Diabetes care [Diabetes Care] 2023 Mar 01; Vol. 46 (3), pp. 593-601.
DOI:	10.2337/dc22-1699
Abstrakt:	Objective: Renin-angiotensin system (RAS) inhibitors decrease the urinary albumin to creatinine ratio (UACR) but are ineffective in up to 40% of patients. We hypothesized that rotation through different drug classes overcomes RAS inhibitor resistance and tested this in a randomized crossover trial. Research Design and Methods: We assigned 26 adults with type 1 diabetes and 37 with type 2 diabetes and UACR between 30 and 500 mg/g and estimated glomerular filtration rate >45 mL/min/1.73 m2 to 4-week treatment periods with telmisartan 80 mg, empagliflozin 10 mg, linagliptin 5 mg, and baricitinib 2 mg in random order, separated by 4-week washout periods. Each participant was then re-exposed for 4 weeks to the drug that induced that individual's largest UACR reduction. Primary outcome was the difference in UACR response to the best-performing drug during the confirmation period versus UACR response to the other three drugs. Results: There was substantial variation in the best-performing drug. Telmisartan was best performing for 33 participants (52%), empagliflozin and linagliptin in 11 (17%), and baricitinib in 8 participants (13%). The individuals' best-performing drug changed UACR from baseline during the first and confirmatory exposures by a mean of -39.6% (95% CI -44.8, -33.8; P < 0.001) and -22.4% (95% CI -29.7, -12.5; P < 0.001), respectively. The Pearson correlation for first versus confirmatory exposure was 0.39 (P = 0.017). The mean change in UACR with the other three drugs was +1.6% (95% CI -4.3%, 8.0%; P = 0.593 versus baseline; difference versus individuals' best-performing drug at confirmation, 30.9% [95% CI 18.0, 45.3]; P < 0.001). Conclusions: We demonstrated a large and reproducible variation in participants' responses to different UACR-lowering drug classes. These data support systematic rotation through different drug classes to overcome therapy resistance to RAS inhibition. (© 2023 by the American Diabetes Association.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu