Key result
Concomitant use of SGLT2 inhibitors and loop diuretics in veterans with type 2 diabetes increased the risk of volume depletion, peaking at 1 to 14 days (IRR 1.82; 95% CI 1.63-2.02).
Why the study?
Loop diuretics manage volume overload in heart failure but may increase volume depletion risk in real-world practice, prompting evaluation of volume depletion risk with concomitant SGLT2i and loop diuretic use.
Does concomitant use of SGLT2 inhibitors and loop diuretics increase the risk of volume depletion in veterans with T2DM?
Observational (n=3,352)
Does concomitant use of SGLT2 inhibitors and loop diuretics increase the risk of volume depletion in veterans with T2DM?
Relative Risk: 1.82 (95% CI 1.63–2.02)
Concomitant prescribing of SGLT2 inhibitors and loop diuretics is associated with an increased risk of volume depletion, particularly in the first 14 days of therapy, highlighting the need for close fluid status monitoring.
May warrant early fluid status monitoring; hypothesis-generating and leaves open causality plus generalizability.
BACKGROUND: Sodium glucose co-transporter 2 inhibitors (SGLT2is) are used to prevent cardiovascular complications in type 2 diabetes mellitus (T2DM) and newly indicated to treat heart failure (HF). Loop diuretics are commonly prescribed to manage volume overload in HF and may increase the risk of volume depletion in real-world practice. This study evaluated the risk of volume depletion following concomitant use of SGLT2is and loop diuretics in veterans. METHODS: Veterans with T2DM were included if they received concomitant loop diuretics and SGLT2is and experienced at least one volume depletion event between December 2012 and December 2019, utilizing a self-controlled case series design. Concomitant prescribing periods were divided into focal windows of 1 to 14 days, 14 to 28 days, and greater than 28 days. Incidence rate ratios (IRR) were estimated using multivariable Poisson regressions adjusted for age and renal function. RESULTS: 3352 patients experienced at least one volume depletion event and were concomitantly prescribed SGLT2is and loop diuretics at least once. The risk of volume depletion increased in the treatment versus control windows during the 1 to 14-day window (IRR = 1.82, 95% CI 1.63-2.02) the 15-to-28-day window (IRR = 1.46, 95% CI 1.28-1.67), and the greater than 28-day window (IRR = 1.22, 95% CI 1.21-1.34). CONCLUSIONS: Concomitant prescribing of SGLT2is and loop diuretics is associated with an increased risk of volume depletion, an effect that attenuates with longer therapy durations. Prescribers need to closely monitor fluid status in patients receiving concomitant therapy, especially those with advancing age or with eGFR below 60.
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Lewellyan et al. (2022) conducted an observational in Type 2 diabetes mellitus (n=3,352). Concomitant SGLT2 inhibitors and loop diuretics vs. Control windows was evaluated on Volume depletion event (IRR 1.82, 95% CI 1.63-2.02). Concomitant use of SGLT2 inhibitors and loop diuretics in veterans with type 2 diabetes increased the risk of volume depletion, peaking at 1 to 14 days (IRR 1.82; 95% CI 1.63-2.02).
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