We appreciate the interest in our work shown by the authors of this letter.1 We fully agree with the comment on the cardiovascular benefits of GLP-1 receptor agonists (GLP-1 RAs) as an excellent treatment option in patients with type 2 diabetes mellitus (T2D) and obesity on peritoneal dialysis (PD). However, to date, there is no published evidence on the experience of using these drugs in PD patients.

By the technical data sheet the administration of GLP-1 RAs analogues are not indicated in patients with estimated glomerular filtration rate (eGFR) < 15 ml/min/1.73 m2. However, it should be remembered that this compound is divided by chemical structure into incretin-mimetics and human GLP-1 analogues; and the latter, which include liraglutide, dulaglutide and semaglutide, are not eliminated by the renal route, but are metabolized by proteolytic enzymes. No specific organ has been identified as the main route of elimination.2,3 Furthermore, the pathway by which GLP-1 RAs may provide renal benefit is currently not well understood, but probably involves a combination of direct and indirect effects, such as stimulation of natriuresis at the proximal tubule level, inhibition of the renin angiotensin system, decreased renal hypoxia, decreased glomerular atherosclerosis, and improved glycemic control, blood pressure and weight reduction, among others.4,5

Therefore, although patients with Stage 5 chronic kidney disease (CKD) (defined by an eGFR < 15 ml/min/1.73 m2) with or without renal replacement therapy (hemodialysis, PD or renal transplantation) have not been included in the large pivotal studies of GLP-1 RAs,6 the results coming from different randomized clinical trials with small sample size and case series, mainly in the advanced CKD,7 hemodialysis8 and renal transplantation9 populations, show that patients undergoing PD could also benefit from the efficacy of GLP-1 RAs in improving glycemic control, lowering blood pressure and weight loss.10,11 Recently, the working group of the “Effect of semaglutide versus placebo on the progression of renal impairment in subjects with type 2 diabetes and chronic kidney disease” (FLOW) study, a Phase 3 clinical trial involving more than 3000 patients with DM2 and moderate-severe CKD (eGFR 25−75 ml/min/1.73 m2 and albumin-creatinine ratio 300−5000 mg/g) (NCT03819153), the first to include kidney disease outcomes as a primary endpoint, which will define the clinical efficacy and renal safety of semaglutide (GLP-1 RAs), expected to be completed in 2024, decided to halt the trial based on the recommendation of the independent data monitoring committee that concluded that the results of an interim analysis met certain predetermined criteria for stopping the trial early due to the efficacy of the drug against the stated endpoints.

Additionally, our group recently published a case series with similar characteristics to the case discussed by the authors of this letter, and we found that the use of GLP-1 RAs in three obese diabetic patients on incremental hemodialysis (iHD) was safe and effective for glycemic and weight control, as well as blood pressure and other control targets that delay diabetic complications. This allowed our patients to maintain one weekly hemodialysis session and facilitate their inclusion in renal transplant waiting lists.8 The latter, in relation to the improvement in obesity parameters, which is a limiting factor for inclusion on the transplant waiting list, as was also noted in another series of two cases published by Touzot et al.12 All these previously mentioned benefits could indirectly contribute to the preservation of residual renal function (RRF), which is fundamental for both patient survival and PD technique survival, without neglecting its effect on the improvement of morbidity and mortality.13

Therefore, we thank and congratulate the authors for their recent case description of their experience using another GLP-1 RA in incremental peritoneal dialysis.