In a study of 29,849 adults with type 2 diabetes, were associated with a lower rate of compared to DPP-4 inhibitors.
SGLT-2 inhibitors were linked to a 23% lower rate of hyperkalemia (hazard ratio 0.77) compared to DPP-4 inhibitors.
This reduction in hyperkalemia included a 24% lower rate of mild hyperkalemia and a 47% lower rate of moderate to severe hyperkalemia.
Seven percent of RAS inhibitor users discontinued therapy, but the initiation of SGLT-2 inhibitors did not influence the rate of RAS inhibitor discontinuation.
About one-third of participants in both groups discontinued treatment within one year.
Results were consistent across various patient subgroups, including sex and cardiovascular disease status.
Simplified
BACKGROUND: Post hoc analyses of clinical trials suggest that sodium-glucose cotransporter-2 inhibitors (SGLT-2i) lower the risk of and facilitate the use of renin-angiotensin system inhibitors (RASi) in people with type 2 diabetes. Whether this is also observed in routine care is unclear. We investigated whether SGLT-2i lowered the risk of hyperkalemia and RASi discontinuation as compared to (DPP-4i).
METHODS: Using the target trial emulation framework, we studied adults with type 2 diabetes (T2D) who started SGLT-2i or DPP-4i in Stockholm, Sweden (2014-2021). The outcomes were incident hyperkalemia (potassium >5.0 mmol/l), mild hyperkalemia (potassium >5-≤5.5 mmol/l), and moderate to severe hyperkalemia (potassium >5.5 mmol/l). Among RASi users, we studied time to RASi discontinuation through evaluation of pharmacy fills. Cox regression with inverse probability of treatment weighting was used to estimate per-protocol hazard ratios (HRs).
RESULTS: In total, 29 849 individuals (15 326 SGLT-2i and 14 523 DPP-4i initiators) were included (mean age 66 years, 37% women). About one-third of participants in each arm discontinued treatment within 1 year. Compared with DPP-4i, SGLT-2i use was associated with a lower rate of hyperkalemia (HR 0.77; 95% CI: 0.64-0.93), including both mild (0.76; 0.62-0.93) and moderate/severe (0.53; 0.40-0.69) hyperkalemia events. Of 19 116 participants who used RASi at baseline, 7% discontinued therapy. Initiation of SGLT-2i vs. DPP-4i was not associated with the rate of RASi discontinuation (0.97; 0.83-1.14). Results were consistent in intention-to-treat analysis and across strata of sex, cardiovascular disease, use of MRA, and use of RASi.
CONCLUSIONS: In patients with diabetes managed in routine clinical care, the use of SGLT-2i was associated with lower rates of hyperkalemia compared with DPP-4i. Possibly because of a relatively high rate of treatment discontinuations, this was not accompanied by higher persistence on RASi therapy.
Key numbers
0.77
Lower Rate of
Adjusted hazard ratio for any events.
7%
Incidence of RASi Discontinuation
Percentage of participants who discontinued RASi therapy.
3.4%
1-Year Absolute Risk of
Absolute risk of in SGLT-2i users after one year.
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The authors do not report any direct disclosure in relation to this study. Unrelated to the study, J.J.C. reports funding to Karolinska Institutet by AstraZeneca, Astellas, Amgen, Vifor Pharma, and NovoNordisk; personal honoraria for lectures by Fresenius Kabi, Baxter Healthcare, and Abbott, and being a member of advisory boards for Astellas, AstraZeneca, and GSK. ME reports funding from AstraZeneca and Astellas pharma, advisory boards from Astellas, and payment for lectures by AstraZeneca, Astellas, Boehringer-Ingelheim, and Vifor Pharma.
