Sodium-glucose cotransporter-2 inhibitor therapy in kidney transplant patients with type 2 or post-transplant diabetes: an observational multicentre study

Background Sodium–glucose cotransporter-2 inhibitors (SGLT2is) have cardioprotective and renoprotective effects. However, experience with SGLT2is in diabetic kidney transplant recipients (DKTRs) is limited. Methods This observational multicentre study was designed to examine the efficacy and safety of SGLT2is in DKTRs. The primary outcome was adverse effects within 6 months of SGLT2i treatment. Results Among 339 treated DKTRs, adverse effects were recorded in 26%, the most frequent (14%) being urinary tract infection (UTI). In 10%, SGLT2is were suspended mostly because of UTI. Risk factors for developing a UTI were a prior episode of UTI in the 6 months leading up to SGLT2i use {odds ratio [OR] 7.90 [confidence interval (CI) 3.63–17.21]} and female sex [OR 2.46 (CI 1.19–5.03)]. In a post hoc subgroup analysis, the incidence of UTI emerged as similar in DKTRs treated with SGLT2i for 12 months versus non-DKTRs (17.9% versus 16.7%). Between baseline and 6 months, significant reductions were observed in body weight [−2.22 kg (95% CI −2.79 to −1.65)], blood pressure, fasting glycaemia, haemoglobin A1c [−0.36% (95% CI −0.51 to −0.21)], serum uric acid [−0.44 mg/dl (95% CI −0.60 to −0.28)] and urinary protein:creatinine ratio, while serum magnesium [+0.15 mg/dl (95% CI 0.11–0.18)] and haemoglobin levels rose [+0.44 g/dl (95% CI 0.28–0.58]. These outcomes persisted in participants followed over 12 months of treatment. Conclusions SGLT2is in kidney transplant offer benefits in terms of controlling glycaemia, weight, blood pressure, anaemia, proteinuria and serum uric acid and magnesium. UTI was the most frequent adverse effect. According to our findings, these agents should be prescribed with caution in female DKTRs and those with a history of UTI. Lay Summary Experience with sodium–glucose cotransporter-2 inhibitor (SGLT2i) treatment in diabetic kidney transplant recipients (DKTRs) is limited, as these agents may increase the risk of kidney graft dysfunction and urinary tract infection (UTI). Recently, however, these drugs have shown clear nephroprotective and cardioprotective effects in non-transplanted individuals with diabetes. The objective of this multicentre study was to describe our experience with SGLT2i treatment in DKTRs. Treatment was effective in controlling glycemia and had the additional benefits of improving weight, blood pressure, anaemia, proteinuria and serum levels of magnesium and uric acid. However, the frequency of UTI was greater than that r