Introduction
Diabetes mellitus (DM) is a serious health problem that has reached alarming proportions, afflicting almost 500 million people worldwide in 2019.1 Of the afflicted people, almost 40% will present with diabetic nephropathy at some point during the evolution of the disease. New drugs for treating DM, which demonstrate both cardiovascular and kidney benefits, have appeared in recent years. These drugs consist of glucagon-like peptide-1 receptor agonists (GLP-1 RA) and sodium glucose luminal transport type 2 inhibitors (SGLT2i).2,3 The mechanism by which these drugs cause kidney benefits appear to be multiple and are not entirely understood. On one hand they most likely would be related to weight reduction, blood pressure reduction or glycemic control.4 Other mechanisms could include anti-inflammatory, anti-arteriosclerotic, and intrarenal mechanisms, such as natriuresis, activation of tubuloglomerular feedback and/or inactivation of the renin-angiotensin system (RAAS).5,6
The renal benefits of GLP-1 RA are based mainly on preservation of glomerular filtration and a reduction in macroalbuminuria.3 Dulaglutide is a GLP-1 RA agonist with a long half-life. In the REWIND cardiovascular safety trial of almost 10,000 patients in which dulaglutide was compared versus \soutplacebo for 5.2 years, a decrease in estimated glomerular filtration rates (eGFR) of 40% to 50% was demonstrated.7 The AWARD-7 trial compared dulaglutide to insulin glargine in patients with type 2 DM (T2DM) and moderate–severe renal failure (mean eGFR=38 ml/min/m2). 8 At 52 weeks of treatment, the dulaglutide group had a lower eGFR drop than the insulin group; the mean eGFR decline was −5.5 ml/min/1.73 m2in the insulin glargine group compared with −0.7 for and −0.50 ml/min /1.73 m2 for the 0.75 and 1.5 mg dulaglutide groups, respectively. In a real-life study over the course of a year, the initiation of insulin glargine versus dulaglutide treatment was compared in a patient base very similar to that in the AWARD-7 trial. The dulaglutide group demonstrated a significant decrease in eGFR (<30%) at one year of treatment. 9
Our group has recently presented real-life data over two years with dulaglutide in a Spanish patient population.10 The present study analyze renal function data based on eGFR in a subgroup of patients and to analyze the relationship between eGFR changes and their baseline values.
MethodsStudy design designed an observational, retrospective, multicenter study in patients with T2DM. Patients were enrolled from three different health areas: (1) San Carlos Clinical Hospital of Madrid; (2) University Hospital of Salamanca; and (3) two districts of Huelva, Huelva-Costa and Condado-Campiña. criteria consisted of several criteria: (1) patients >18 years with a diagnosis of DM2 and (2) receiving dulaglutide treatment at a weekly dose of 1.5 mg with no interruptions in treatment with this drug for at least 36 months (M) between December 2015 and December 2019 based on electronic prescriptions and a medical records review. Patients who did not fulfill these criteria were excluded. primary endpoint was evaluation of dulaglutide efficacy with respect to eGFR preservation in patients receiving dulaglutide treatment for 36M. To measure this parameter, eGFR was analyzed at baseline and 12, 24, and 36M after starting the drug. eGFR evaluation (measured by MDRD-411) differences according to antidiabetic treatment was the secondary endpoint. Other endpoints were changes/improvements in fasting blood glucose, glycosylated hemoglobin (HbA1c), and weight at the end of the study. Analyzed variables included age, gender, eGFR, fasting blood glucose, HbA1c, weight, and antidiabetic treatment at study initiation. The study received the approval of the ethics committee of the study reference center and was in compliance with the Helsinki declaration. Every modification in the management of the patients was decided by the treating physician.