Diuretics and risk of major adverse limb events in patients with type-2 diabetes: An observational retrospective study

Aim

In patients with type-2 diabetes mellitus (T2DM), sodium-glucose co-transporter 2 inhibitors are suspected to increase the risk of amputation. “Traditional” diuretics may increase major adverse limb events (MALEs), but the evidence is weak. We studied the association between common diuretics (i.e. thiazides, loop- and potassium-sparing diuretics) and MALEs/amputations in patients with T2DM.

Methods

Consecutive T2DM patients without cardiovascular history referred to our center for cardiovascular check-ups were retrospectively studied. Follow-up data on MALEs were collected. We used Cox models to assess the association between diuretics and MALEs, or amputation alone. A propensity score with inverse probability of diuretic treatment weighting (IPTW) analysis was performed.

Results

We studied 1309 patients, (59.5 ± 10.7 years, 51 % females) with diabetes duration of 9.1 ± 8.5 years, among whom 402 (30 %) were taking diuretics. During a follow-up of 3.8 ± 1.64 years, 121 (9.1 %) had MALEs, including 19 (1.4 %) amputations. Death occurred in 111 patients and the proportion of death was significantly different between groups: patients with diuretics n = 49, 44.1% vs patients without diuretics n = 62, 55.9 %, P = 0.001. Diuretics, in multivariable analysis, were associated with MALEs (aHR[95 %CI] 1.96[1.32;2.91] P = 0.001), even after adjustment on propensity score (aHR 1.66[1.08;2.56] P = 0.02) and IPTW analysis (aHR 1.76[1.67;1.84] P < 0.0001). This risk was particularly increased in case of an abnormal ankle-brachial index (aHR 2.29[1.32;3.96], P = 0.003) at baseline. Looking at diuretic classes separately, the adjusted risk was increased with loop diuretics (aHR 2.56[1.16;5.64] P = 0.020), thiazides (aHR 2.21[1.37;3.57] P = 0.001) or potassium sparing diuretics (aHR 2.56[1.16;5.64] P = 0.020).

Conclusion

Diuretic treatment weighting may be associated with increased risk of MALEs. We identified several markers of increased risk of limb events where the use of diuretics should be considered with caution.