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.