Tirzepatide and prevention of chronic kidney disease

Abstract

Chronic kidney disease; Diabetes mellitus; Obesity

Malaltia renal crònica; Diabetis mellitus; Obesitat

Enfermedad renal crónica; Diabetes mellitus; Obesidad

Tirzepatide is a twincretin recently approved to improve glycemic control in type 2 diabetes mellitus (T2DM). More specifically, tirzepatide is an agonist of both the glucose-dependent insulinotropic polypeptide (GIP) and the glucagon-like peptide-1 (GLP1) receptors. In recent clinical trials in persons with obesity or overweight with associated conditions, tirzepatide decreased body weight and other cardiorenal risk factors (blood pressure, low-density lipoprotein cholesterol, glycated hemoglobin and albuminuria). Moreover, in a post hoc analysis of the SURPASS-4 randomized clinical trial, tirzepatide decreased albuminuria and total estimated glomerular filtration rate (eGFR) slopes and nearly halved the risk of a pre-specified composite kidney endpoint (eGFR decline ≥40%, renal death, kidney failure or new-onset macroalbuminuria) in participants with T2DM and high cardiovascular risk when compared with insulin glargine. Similar to other kidney-protective drugs, tirzepatide, alone or combined with sodium-glucose co-transporter 2 inhibitors, caused an early dip in eGFR. Moreover, tirzepatide also decreased eGFR slopes in participants with eGFR >60 mL/min/1.73 m2 or with normoalbuminuria. We now review the potential kidney health implications of tirzepatide, addressing its structure and function, relationship to current GLP1 receptor agonists, impact of recent results for the treatment and prevention of kidney disease, and expectations for the future.

FIS/Fondos FEDER (PI18/01366, PI19/00588, PI19/00815, PI20/00744, DTS18/00032, ERA-PerMed-JTC2018 KIDNEY AT390 TACK AC18/00064 and PERSTIGAN AC18/00071, ISCIII-RETIC REDinREN RD016/0009), Sociedad Española de Nefrología, Sociedad Madrileña de Nefrología (SOMANE), FRIAT, Comunidad de Madrid en Biomedicina (B2017/BMD-3686 and CIFRA2-CM). Instituto de Salud Carlos III (ISCIII) RICORS program (RICORS2040-395 , RD21/0005/0001) and SPACKDc PMP21/00109, FEDER funds funded by European Union—Next Generation EU’, Mecanismo para la Recuperación y la Resiliencia (MRR) and RD16/0009.