Safety Profile of SGLT2 Inhibitor and Glucagon-Like Peptide 1 Receptor Agonist (GLP-1 RA) Use in Patients with CKD

Background: The novel hypoglycemic agents SGLT2i and GLP-1RA have demonstrated combined reno and cardiovascular protective and mortality benefits. Multiple studies have extensively assessed the safety analyses and adverse events associated with these agents among patients with diabetes and cardiovascular disease. However, there is a paucity of data on the safety analyses of these agents among patients with chronic kidney disease. Methods: TriNetX database was used to determine patients aged > 18 with CKD (eGFR 30-89) within the USA collaborative network from Jan 1st, 2015, to Dec 31st, 2023. The SGLT2i and GLP-1RA users and nonusers were propensity-scored matched on factors such as Diabetes, HTN, Heart failure, hyperlipidemia, obesity, use of Insulin, sulfonylureas, metformin, ACEi/ARBs, diuretics, and other hypoglycemic agents. Results: Our results indicate that of 295,798 SGLT2i users and 9885755 non-users, 294567 patients were propensity-scored matched in both groups. The risk of UTI 3.7% (10062) in SGLT2i users, compared to 6.89% (17964) in non-users, genitourinary infections 1.8% (5284) vs. 2.7% (7803), Hypoglycemia 1.08% (3126) vs 1.5% (4358), bone fractures 0.23% (687) vs. 0.5% (1471), limb amputation 0.03% (104) vs 0.06% (192), ketoacidosis 0.14% (435) vs. 0.16 % (457), volume depletion 2.5% (7104) vs. 4% (11639). The risks of Vulvovaginitis are 0.007% (22) vs. 0.008% (23), vaginal candidiasis 3.6% (9978) vs. 3.8% (10837), Fournier gangrene 0.01% (40) vs. 0.019 % (56) were almost similar in both SGLT2I users and nonusers respectively. The results of adverse events comparison of GLP-1RA users with non users is shown in figure 1. Conclusion: Overall, the results of our study demonstrate that the risks of adverse events in the SGLT2i and GLP-1RA users in patients with chronic kidney disease are relatively lower than in the nonuser groups.