SGLT2i and GLP-1 RA therapy in type 1 diabetes and reno-vascular outcomes: a real-world study.

Anson, Matthew, Zhao, Sizheng S, Austin, Philip, Ibarburu, Gema H, Malik, Rayaz A and Alam, Uazman ORCID: 0000-0002-3190-1122 (2023) SGLT2i and GLP-1 RA therapy in type 1 diabetes and reno-vascular outcomes: a real-world study. Diabetologia, 66 (10). pp. 1869-1881.

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Official URL: http://dx.doi.org/10.1007/s00125-023-05975-8

Abstract

<h4>Aims/hypothesis</h4>Insulin is the primary treatment for type 1 diabetes. However, alternative glucose-lowering therapies are used adjunctively, but importantly are off-label in type 1 diabetes. Little work has previously been undertaken to evaluate safety with long-term efficacy and cardio-renal benefits of such therapies. We sought to investigate the real-world impact of sodium-glucose cotransporter 2 inhibitor (SGLT2i) and glucagon-like peptide-1 receptor agonist (GLP-1 RA) therapy in individuals with type 1 diabetes in relation to effect on blood glucose levels, adverse events and cardio-renal outcomes.<h4>Methods</h4>We performed a retrospective cohort study of all patients aged 18 or over with type 1 diabetes on the TriNetX platform, a global collaborative network providing access to real-time, anonymised medical records. We included patients who had been treated with an SGLT2i or GLP-1 RA for at least 6 months and analysed the efficacy, safety and cardio-renal outcomes 5 years after initiation of therapy.<h4>Results</h4>We identified 196,691 individuals with type 1 diabetes, 13% of whom were treated with adjunctive glucose-lowering therapy in addition to insulin. Included in the core analysis were 1822 patients treated with a GLP-1 RA and 992 individuals treated with an SGLT2i. Both agents provided clinically meaningful reductions in HbA<sub>1c</sub> (-2.6 mmol/mol [-0.2%] with SGLT2i and -5.4 mmol/mol [-0.5%] with GLP-1 RA). The SGLT2i treated cohort showed preservation of eGFR over a 5-year period compared with the GLP-1 RA treated cohort (+3.5 ml/min per 1.73 m<sup>2</sup> vs -7.2 ml/min per 1.73 m<sup>2</sup>, respectively), including patients with established chronic kidney disease (CKD). The SGLT2i treated cohort experienced higher rates of diabetic ketoacidosis (DKA) (RR 2.08 [95% CI 1.05, 4.12] p=0.0309) and urinary tract infection/pyelonephritis (RR 2.27 [95% CI 1.12, 4.55] p=0.019) compared with the GLP-1 RA treated cohort. However, the SGLT2i treated cohort were less likely to develop heart failure (RR 0.44 [95% CI 0.23, 0.83] p=0.0092), CKD (RR 0.49 [95% CI 0.28, 0.86] p=0.0118) and be hospitalised for any cause (RR 0.59 [95% CI 0.46, 0.76] p≤0.0001) when compared with the GLP-1 RA treated cohort.<h4>Conclusions/interpretation</h4>Both SGLT2is and GLP-1 RAs have potential benefits as adjunctive agents in type 1 diabetes. SGLT2is provide cardio-renal benefits, despite an increase in the risk of DKA and urinary tract infection compared with GLP-1 RA therapy. Long-term evaluation of the efficacy and safety of these adjunctive therapies is required to guide their use in individuals with type 1 diabetes.

Item Type:	Article
Uncontrolled Keywords:	Chronic kidney disease, Diabetic ketoacidosis, GLP-1 RA, Heart failure, SGLT2i, Type 1 diabetes
Divisions:	Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Life Courses and Medical Sciences
Depositing User:	Symplectic Admin
Date Deposited:	22 Aug 2023 09:32
Last Modified:	09 Sep 2023 14:31
DOI:	10.1007/s00125-023-05975-8
Open Access URL:	https://doi.org/10.1007/s00125-023-05975-8
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3172283