Empagliflozin in posttransplantation diabetes mellitus: A prospective, interventional pilot study on glucose metabolism, fluid volume, and patient safety

Abstract

The safety and efficacy of sodium‐glucose cotransporter 2 inhibitors in posttransplantation diabetes mellitus is unknown. We converted stable kidney transplant patients to 10 mg empagliflozin, aiming at replacing their insulin therapy (<40 IU/d). N = 14 participants (the required sample size) completed the study visits through 4 weeks and N = 8 through 12 months. Oral glucose tolerance test (OGTT)–derived 2‐hour glucose (primary end point) increased from 232 ± 82 mg/dL (baseline) to 273 ± 116 mg/dL (4 weeks, P = .06) and to 251 ± 71 mg/dL (12 months, P = .41). Self‐monitored blood glucose and hemoglobin A1c were also clinically inferior with empagliflozin monotherapy, such that insulin was reinstituted in 3 of 8 remaining participants. Five participants (2 of them dropouts) vs nine of 24 matched reference patients developed bacterial urinary tract infections (P = .81). In empagliflozin‐treated participants, oral glucose insulin sensitivity decreased and beta‐cell glucose sensitivity increased at the 4‐week and 12‐month OGTTs. Estimated glomerular filtration rate and bioimpedance spectroscopy‐derived extracellular and total body fluid volumes decreased by 4 weeks, but recovered. All participants lost body weight. No participant developed ketoacidosis; 1 patient developed balanitis. In conclusion, although limited by sample size and therefore preliminary, these results suggest that empagliflozin can safely be used as add‐on therapy, if posttransplant diabetes patients are monitored closely (NCT03113110).

Effect of SGLT2 inhibitors on body composition, fluid status and renin–angiotensin–aldosterone system in type 2 diabetes: a prospective study using bioimpedance spectroscopy

“…Extracellular water was reduced rapidly and significantly after 3 days, but had returned to baseline value when measured after three and 6 months. In a cohort of post-transplant diabetes mellitus, Schwaiger et al[11] also found a decrease of extracellular fluid after 4 weeks and extracellular water returned to baseline value in the further course. In Japanese patients treated with ipragliflozin, Iizuka et al[8] found a reduction of total body water by − 0.43 kg at 4 weeks, and a rising tendency at 12 weeks (− 0.37 kg), compared to baseline, respectively, with changes of body fluid mainly caused by extracellular water and no significant changes of intracellular water; however, changes of volume status during the first days Friedman-Test: Χ² (10) = 5.182 p = 0*p < 0.008 (significant with Bonferroni correcƟon); #p < 0.05 Course of serum aldosterone concentration (a) and plasma renin activity (b) under treatment with SGLT2 inhibitors.…”

“…Previous investigations of changes in body composition under SGLT2 inhibitors mainly relied on calculated indices or x-ray absorptiometry [5][6][7]. In contrast, quantitative measurements of body composition have only lately been performed in a few cohorts [8][9][10][11]. Early changes of body composition during the first days after initiation of SGTL2 inhibitors have not been investigated yet.…”

Management of post‐transplant diabetes: immunosuppression, early prevention, and novel antidiabetics

“…Based on the rationale that novel antidiabetic agents have been shown to be immensely beneficial in the general population with T2DM, the SGLT2i empagliflozin was used at the Vienna transplant center in patients with PTDM after kidney transplantation, in a study which resulted in the formally first publication on this subject (the EMpagliflozin in Post‐TRAnsplant Diabetes Mellitus [EMPTRA‐DM] pilot study [111]). Only a few months later, the transplant center in Oslo also published a randomized controlled study on empagliflozin administration after kidney transplantation (EMPA‐Renal Tx [112]), and several other studies have followed on kidney [113‐115] and heart [116,117] transplant patients.…”

Two Japanese patients with stage G3b chronic kidney disease and impaired glucose metabolism after renal transplantation successfully treated with empagliflozin

“…In both cases, renal function did not decrease and UACR decreased after administration of empagliflozin. Regarding the decrease in UACR, it is possible that the improvement of tubuloglomerular feedback associated with natriuresis by empagliflozin was involved in the case of also CKD stage3a [15,20,22,25]. The decrease in UACR in both cases may lead to renal protection.…”

“…Recently, however, studies have addressed the issue of SGLT2 inhibitor administration to renal transplant patients [14]. For example, Schwaiger et al [15] assessed the impact of replacing insulin with empagliflozin 10 mg/day in 14 stable kidney transplantation patients with diabetes mellitus. Although the administration of empagliflozin alone decreased glucose and HbA1c levels, the patients lost an average of 1.6 kg over 4 weeks.…”