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

被引:39
作者
Anson, Matthew [1 ,2 ]
Zhao, Sizheng S. [3 ]
Austin, Philip [4 ]
Ibarburu, Gema H. [4 ]
Malik, Rayaz A. [5 ]
Alam, Uazman [1 ,2 ,6 ]
机构
[1] Univ Liverpool, Diabet & Endocrinol Res & Pain Res Inst, Inst Life Course & Med Sci, Liverpool, England
[2] Liverpool Univ Hosp NHS Fdn Trust, Liverpool, England
[3] Univ Manchester, Fac Biol Med & Hlth, Ctr Epidemiol Versus Arthrit, Manchester Acad Hlth Sci Ctr, Manchester, England
[4] TriNetX LLC, Cambridge, MA USA
[5] Weill Cornell Med Qatar, Doha, Qatar
[6] Staffordshire Univ, Ctr Biomech & Rehabil Technol, Stoke On Trent, England
关键词
Chronic kidney disease; Diabetic ketoacidosis; GLP-1; RA; Heart failure; SGLT2i; Type; 1; diabetes; INSULIN-TREATMENT; GLYCEMIC CONTROL; DOUBLE-BLIND; EFFICACY; SAFETY; LIRAGLUTIDE; INHIBITORS; DAPAGLIFLOZIN; KETOACIDOSIS; EXENATIDE;
D O I
10.1007/s00125-023-05975-8
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Aims/hypothesis 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.Methods 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.Results 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(1c) (-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(2) vs -7.2 ml/min per 1.73 m(2), 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 & LE;0.0001) when compared with the GLP-1 RA treated cohort.Conclusions/interpretation 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.
引用
收藏
页码:1869 / 1881
页数:13
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