Long-term benefits of dapagliflozin on renal outcomes of type 2 diabetes under routine care: a comparative effectiveness study on propensity score matched cohorts at low renal risk

Gian Paolo Fadini; Enrico Longato; Mario Luca Morieri; Stefano Del Prato; Angelo Avogaro; Anna Solini; DARWIN-Renal Study Investigators

doi:10.1016/j.lanepe.2024.100847

Long-term benefits of dapagliflozin on renal outcomes of type 2 diabetes under routine care: a comparative effectiveness study on propensity score matched cohorts at low renal risk

Lancet Reg Health Eur. 2024 Feb 1:38:100847. doi: 10.1016/j.lanepe.2024.100847. eCollection 2024 Mar.

Authors

Gian Paolo Fadini^{1

2}, Enrico Longato³, Mario Luca Morieri¹, Stefano Del Prato⁴, Angelo Avogaro¹, Anna Solini⁵; DARWIN-Renal Study Investigators

Collaborators

DARWIN-Renal Study Investigators:
Mariella Baldassarre, Agostino Consoli, Sara Morganet, Antonella Zugaro, Marco Giorgio Baroni, Francesco Andreozzi, Adriano Gatti, Adriano Gatti, Stefano De Riu, Andrea Del Buono, Raffaella Aldigeri, Riccardo Bonadonna, Alessandra Dei Cas, Angela Vazzana, Monica Antonini, Valentina Moretti, Patrizia Li Volsi, Miranda Cesare, Giorgio Zanette, Silvia Carletti, Paola D'Angelo, Gaetano Leto, Frida Leonetti, Luca D'Onofrio, Ernesto Maddaloni, Raffaella Buzzetti, Simona Frontoni, Giselle Cavallo, Susanna Morano, Tiziana Filardi, Umberto Capece, Andrea Giaccari, Antonio C Bossi, Giancarla Meregalli, Fabrizio Querci, Alessia Gaglio, Veronica Resi, Emanuela Orsi, Stefano Fazion, Ivano G Franzetti, Cesare Berra, Silvia Manfrini, Gabriella Garrapa, Giulio Lucarelli, Lara Riccialdelli, Elena Tortato, Marco Zavattaro, Gianluca Aimaretti, Franco Cavalot, Guglielmo Beccuti, Fabio Broglio, Bruno Fattor, Giuliana Cazzetta, Olga Lamacchia, Anna Rauseo, Salvatore De Cosmo, Rosella Cau, Mariangela Ghiani, Antonino Di Benedetto, Antonino Di Pino, Salvatore Piro, Francesco Purrello, Lucia Frittitta, Agostino Milluzzo, Giuseppina Russo

Affiliations

¹ Division of Metabolic Diseases, Department of Medicine, University of Padova, 35128 Padova, Italy.
² Laboratory of Experimental Diabetology, Veneto Institute of Molecular Medicine, 35128 Padova, Italy.
³ Department of Information Engineering, University of Padova, 35100 Padua, Italy.
⁴ Department of Clinical & Experimental Medicine, University of Pisa and Sant'Anna School of Advanced Studies, 56126 Pisa, Italy.
⁵ Department of Surgical, Medical, Molecular and Critical Area Pathology, University of Pisa, Italy.

Abstract

Background: Despite the overall improvement in care, people with type 2 diabetes (T2D) experience an excess risk of end-stage kidney disease. We evaluated the long-term effectiveness of dapagliflozin on kidney function and albuminuria in patients with T2D.

Methods: We included patients with T2D who initiated dapagliflozin or comparators from 2015 to 2020. Propensity score matching (PSM) was performed to balance the two groups. The primary endpoint was the change in estimated glomerular filtration rate (eGFR) from baseline to the end of observation. Secondary endpoints included changes in albuminuria and loss of kidney function.

Findings: We analysed two matched groups of 6197 patients each. The comparator group included DPP-4 inhibitors (40%), GLP-1RA (22.3%), sulphonylureas (16.1%), pioglitazone (8%), metformin (5.8%), or acarbose (4%). Only 6.4% had baseline eGFR <60 ml/min/1.73 m² and 15% had UACR >30 mg/g. During a mean follow-up of 2.5 year, eGFR declined significantly less in the dapagliflozin vs comparator group by 1.81 ml/min/1.73 m² (95% C.I. from 1.13 to 2.48; p < 0.0001). The mean eGFR slope was significantly less negative in the dapagliflozin group by 0.67 ml/min/1.73 m²/year (95% C.I. from 0.47 to 0.88; p < 0.0001). Albuminuria declined significantly in new-users of dapagliflozin within 6 months and remained on average 44.3 mg/g lower (95% C.I. from -66.9 to -21.7; p < 0.0001) than in new-users of comparators. New-users of dapagliflozin had significantly lower rates of new-onset CKD, loss of kidney function, and a composite renal outcome. Results were confirmed for all SGLT2 inhibitors, in patients without baseline CKD, and when GLP-1RA were excluded from comparators.

Interpretation: Initiating dapagliflozin improved kidney function outcomes and albuminuria in patients with T2D and a low renal risk.

Funding: Funded by the Italian Diabetes Society and partly supported by a grant from AstraZeneca.

Keywords: Chronic kidney disease; Observational; Prevention; SGLT2 inhibitors; Type 2 diabetes.