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. 2024 Mar;105(3):618-628.
doi: 10.1016/j.kint.2023.11.025. Epub 2023 Dec 13.

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

Edouard L Fu  1 , Julianna Mastrorilli  1 , Katsiaryna Bykov  1 , Deborah J Wexler  2 , Alexander Cervone  1 , Kueiyu Joshua Lin  3 , Elisabetta Patorno  1 , Julie M Paik  4
Affiliations

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

Edouard L Fu et al. Kidney Int. 2024 Mar.

Abstract

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.

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

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Conflict of interest statement

Conflict of Interest Disclosures: Dr. Patorno is investigator of an investigator-initiated grant to the Brigham and Women’s Hospital from Boehringer Ingelheim, not directly related to the topic of the submitted work. Dr. Wexler reports serving on Data Monitoring Committees for Novo Nordisk not related to the topic of this work. No other potential conflicts of interest relevant to this article were reported.

Figures

Figure 1.
Figure 1.
Cumulative incidence curves for (A) SGLT-2i versus DPP-4i, (B) GLP-1RA vs. DPP-4i and (C) SGLT-2i vs. GLP-1RA on risk of hyperkalemia diagnosis in inpatient or outpatient setting after 1:1 propensity score matching.
Figure 2.
Figure 2.
Comparative effectiveness of (A) SGLT-2i versus DPP-4i (B) GLP-1RA vs. DPP-4i and (C) SGLT-2i vs. GLP-1RA on risk of hyperkalemia diagnosis in inpatient or outpatient setting among subgroups after 1:1 propensity score matching. ACE = angiotensin-converting enzyme inhibitor; ARB = angiotensin II receptor blockers; ARNI = angiotensin receptor/neprilysin inhibitor; CI = confidence interval; CVD = cardiovascular disease; DPP-4i = dipeptidyl peptidase-4 inhibitor; GLP-1RA = glucagon-like peptide-1 receptor agonist; IR = Incidence Rate; MRA = mineralocorticoid receptor antagonists; PY = person-years; SGLT-2i = sodium-glucose cotransporter-2 inhibitor. *Only data from CMS Medicare
Figure 2.
Figure 2.
Comparative effectiveness of (A) SGLT-2i versus DPP-4i (B) GLP-1RA vs. DPP-4i and (C) SGLT-2i vs. GLP-1RA on risk of hyperkalemia diagnosis in inpatient or outpatient setting among subgroups after 1:1 propensity score matching. ACE = angiotensin-converting enzyme inhibitor; ARB = angiotensin II receptor blockers; ARNI = angiotensin receptor/neprilysin inhibitor; CI = confidence interval; CVD = cardiovascular disease; DPP-4i = dipeptidyl peptidase-4 inhibitor; GLP-1RA = glucagon-like peptide-1 receptor agonist; IR = Incidence Rate; MRA = mineralocorticoid receptor antagonists; PY = person-years; SGLT-2i = sodium-glucose cotransporter-2 inhibitor. *Only data from CMS Medicare
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