A population-based cohort defined risk of hyperkalemia after initiating SGLT-2 inhibitors, GLP1 receptor agonists or DPP-4 inhibitors to patients with chronic kidney disease and type 2 diabetes.

Publisher: Elsevier Country of Publication: United States NLM ID: 0323470 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1523-1755 (Electronic) Linking ISSN: 00852538 NLM ISO Abbreviation: Kidney Int Subsets: MEDLINE

Publication: 2016- : New York : Elsevier
Original Publication: New York, Springer-Verlag.

Diabetes Mellitus, Type 2*/complications ; Diabetes Mellitus, Type 2*/drug therapy ; Dipeptidyl-Peptidase IV Inhibitors*/adverse effects ; Sodium-Glucose Transporter 2 Inhibitors*/adverse effects ; Hyperkalemia*/chemically induced ; Hyperkalemia*/epidemiology ; Hyperkalemia*/drug therapy ; Renal Insufficiency, Chronic*/drug therapy; Humans ; Aged ; United States/epidemiology ; Hypoglycemic Agents/adverse effects ; Cohort Studies ; Medicare ; Glucagon-Like Peptide-1 Receptor

Hyperkalemia is a common adverse event in patients with chronic kidney disease (CKD) and type 2 diabetes and limits the use of guideline-recommended therapies such as renin-angiotensin system inhibitors. Here, we evaluated the comparative effects of sodium-glucose cotransporter-2 inhibitors (SGLT-2i), glucagon-like peptide-1 receptor agonists (GLP-1RA) and dipeptidyl peptidase-4 inhibitors (DPP-4i) on the risk of hyperkalemia. We conducted a population-based active-comparator, new-user cohort study using claims data from Medicare and two large United States commercial insurance databases (April 2013-April 2022). People with CKD stages 3-4 and type 2 diabetes who newly initiated SGLT-2i vs. DPP-4i (141671 patients), GLP-1RA vs. DPP-4i (159545 patients) and SGLT-2i vs. GLP-1RA (93033 patients) were included. The primary outcome was hyperkalemia diagnosed in inpatient or outpatient settings. Secondary outcomes included hyperkalemia diagnosed in inpatient or emergency department setting, and serum potassium levels of 5.5 mmol/L or more. Pooled hazard ratios and rate differences were estimated after propensity score matching to adjust for over 140 potential confounders. Initiation of SGLT-2i was associated with a lower risk of hyperkalemia compared with DPP-4i (hazard ratio 0.74; 95% confidence interval 0.68-0.80) and contrasted to GLP-1RA (0.92; 0.86-0.99). Compared with DPP-4i, GLP-1RA were also associated with a lower risk of hyperkalemia (0.80; 0.75-0.86). Corresponding absolute rate differences/1000 person-years were -24.8 (95% confidence interval -31.8 to -17.7), -5.0 (-10.9 to 0.8), and -17.7 (-23.4 to -12.1), respectively. Similar findings were observed for the secondary outcomes, among subgroups, and across single agents within the SGLT-2i and GLP-1RA classes. Thus, SGLT-2i and GLP-1RA are associated with a lower risk of hyperkalemia than DPP-4i in patients with CKD and type 2 diabetes, further supporting the use of these drugs in this population.
(Copyright © 2023 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

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RF1 AG063381 United States AG NIA NIH HHS; R01 AG075335 United States AG NIA NIH HHS; R01 AR075117 United States AR NIAMS NIH HHS; K08 AG055670 United States AG NIA NIH HHS; U01 FD007213 United States FD FDA HHS; K01 AG068365 United States AG NIA NIH HHS

Keywords: chronic kidney disease; dipeptidyl peptidase-4 inhibitors; glucagon-like peptide-1 receptor agonists; hyperkalemia; sodium-glucose cotransporter-2 inhibitors; type 2 diabetes

0 (Dipeptidyl-Peptidase IV Inhibitors)
0 (Sodium-Glucose Transporter 2 Inhibitors)
0 (Hypoglycemic Agents)
0 (Glucagon-Like Peptide-1 Receptor)

Date Created: 20231215 Date Completed: 20240226 Latest Revision: 20240310

20240310

PMC10922914

10.1016/j.kint.2023.11.025

38101515