Efficacy and safety of canagliflozin in kidney transplant patients

Abstract

Introduction: There is no report of efficacy and safety of canagliflozin, a sodium glucose cotransporter 2 (SGLT2) inhibitor in post kidney transplant patients with diabetes. Materials and Methods: A pilot study was undertaken in stable renal transplant recipients with preexisting diabetes or new onset diabetes after transplantation (NODAT) to look at the efficacy of SGLT2 inhibitor, cangliflozin. With the introduction of canagliflozin (100 mg), the dose of insulin and/or other oral hypoglycemic agents was reduced if the blood sugar control improved. The parameters monitored were body weight, blood pressure (BP), serum creatinine, HbA1c, and tacrolimus trough level. Safety was assessed by adverse event (AE) reports. Each patient was followed for a minimum period of 6 months. Results: The study included 24 (23 males and 1 females) stable kidney transplant patients with diabetes. The mean age of the patients was 53.8 ± 7.12 years. The mean body weight of study subjects was 78.6 ± 12.1 kg before and 76.1 ± 11.2 kg 6 months after starting canagliflozin ( P < 0.05). The mean systolic and diastolic BP (mm Hg) was 142 ± 21 and 81 ± 9 before and 134 ± 17 and 79 ± 8, 6 months after starting canagliflozin, respectively ( P < 0.05 for systolic BP). There was no significant change in creatinine level (mg/dL). It was 1.1 ± 0.2 before and 1.1 ± 0.3 after starting canagliflozin. The tacrolimus level (ng/mL) was 6.7 ± 3.7 before and 6.1 ± 2, 6 months after starting canagliflozin. The mean HbA1c before was 8.5 ± 1.5%. At 6 months, it was 7.6 ± 1%. Hypoglycemia was not seen. There was no increase in infections. Conclusion: Canagliflozin provided reductions in body weight, BP, HbA1c, and the requirement of other hypoglycemic agents without any hypoglycemic episodes and without significant AEs.

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

“…Urinary dipstick tests, preferably performed by the patients themselves, while taking empagliflozin, may be particularly advisable. In support of these data from Vienna and Oslo, 5 additional publications, all case series and retrospective studies [113‐117], have been subsequently published for the SGLT2is so far (summarized in Table 1, second row). Two of these publications reported on empagliflozin in heart transplant patients [116,117].…”

“…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.…”

“…It would therefore be trend‐setting to be able to demonstrate for SGLT2is and/or GLP1‐RAs in PTDM patients after solid organ transplantation that they modify progression of kidney disease, cardiovascular disease, and heart failure, perhaps translating into improved clinical outcomes, including mortality. In the case of the SGLT2is, several small studies have been conducted after transplantation, two of them prospective [111‐117]. These studies show that SGLT2is can potentially be used in post‐transplant diabetes, but the patients should undergo close monitoring.…”

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

“…Five of the patients had urinary tract infections, though that rate was similar to the controls. Four other groups also reported good results for SGLT-2 inhibitors in diabetic kidney transplant patients [16][17][18][19]. Common features noted in these five reports are that administration of SGLT2 inhibitors led to weight loss, and there were no significant changes in eGFR and no serious adverse events.…”

Management of metabolic alterations in adult kidney transplant recipients: A joint position statement of the Italian Society of Nephrology (SIN), the Italian Society for Organ Transplantation (SITO) and the Italian Diabetes Society (SID)

“…Two studies have assessed the role of SGLT-2i in the management of PTDM. The first study was a small, single-arm pilot trial that enrolled 25 KTRs with PTDM (20 had pre-existing diabetes) who were prescribed canagliflozin on top of standard antihyperglycaemic treatment [79]. Canagliflozin was well tolerated, and significantly reduced blood pressure and HbA1c, without affecting renal function nor tacrolimus levels.…”