Dulaglutide in Patients with Diabetes and Kidney Disease | IJNRD

Introduction

Diabetes is a leading cause of end-stage renal disease worldwide, and chronic kidney disease (CKD) is estimated to occur in nearly half of patients with type 2 diabetes (T2D) and one-third of patients with type 1 diabetes.¹ Glucagon-like peptide-1 receptor agonists (GLP-1 RA) are a vital therapy for glycemic control in T2D, and is being studied for improving renal outcomes in T2D and CKD. In existing clinical trials, dulaglutide was effective in improving glycemic control, but there were limited patients with moderate to advanced CKD included in these studies.² This need is further highlighted in recent Kidney Disease Improving Global Outcomes guidelines, which calls for further studies on the efficacy and safety of GLP-1 RA in the setting of moderate-advanced CKD.³ Existing real-world studies on dulaglutide have limitations including a homogenous cohort and limited patients with stage 4–5 CKD.^4,5 To meet this gap, we conducted a retrospective study of the tolerance and efficacy of dulaglutide in patients with diabetes and moderate-advanced CKD.

Materials and Methods

This retrospective observational study was approved by the Washington University Institutional Review Board (IRB). A full waiver for patient consent prior to review of records was obtained from the IRB as the study posed no more than minimal risk to individual privacy. Patient data confidentiality was maintained, and extracted data were de-identified before analysis. This study complies with the Declaration of Helsinki. We retrospectively identified outpatient dulaglutide prescriptions in patients with T2D, CKD stages 3–5 based on estimated glomerular filtration rate (eGFR), and dulaglutide use for ≥3 months from 2016 to 2023 across the Barnes Jewish Hospital system. T2D was diagnosed based on clinical diagnosis and/or hemoglobin A1c (HbA1c). Primary outcomes included patient reported side effects (gastrointestinal (GI) or allergic reactions) and hypoglycemia as documented in provider notes. Additional outcomes included change in HbA1c, weight, and body mass index (BMI) after first year of use. Continuous variables were presented as mean ± standard deviation. Fisher’s exact test was used to compare categorical CKD stage if the patient stopped due to a side effect. Chi-squared test for equal proportions was used to test for an overall difference among the three stages. Continuous variables were assessed by paired t-test. Results were significant if P≤0.05. Analyses were completed with SAS v9.4, (Cary, NC, USA).

Results

One hundred forty-nine patients with CKD received dulaglutide from 2016–2023. Ninety-seven percent of patients had T2D while 3% had posttransplant diabetes. Mean age was 68.2 ± 9.6 years, 90 (60%) were female. Seventy-eight (52%) patients identified as white, 67 (45%) as black, and four (3%) as other. One hundred nine (73%) patients had concomitant use of angiotensin-converting enzyme inhibitor or angiotensin II receptor blockers, and 28 (19%) used sodium glucose co-transporter 2 inhibitors. Over a treatment duration of 28.5 ± 21.5 months, the mean eGFR changed from 27.8 ± 12.8 to 18.6 ± 7.5 mL/min/1.73 m² (PP

To evaluate for side effects, we found 28 (19%) of all patients with moderate-severe CKD (stage 3–5) dexperienced one or more side effects (Table 1). There was no difference in the frequency of side effects based on stage of CKD (P=0.747). The most common side effects were nausea/vomiting in 16 (57%), diarrhea/constipation in nine (32%), while a smaller cohort had serious side effects including cholecystectomy in three (11%) or pancreatitis in one (4%). Of the 28 patients who experienced side effects, 11 discontinued dulaglutide due to the side effect after an average of 21.1 ± 18.7 months, most commonly due to nausea/vomiting.

We further evaluated the rate of hypoglycemia in the study population (Table 1). Forty-one (28%) of the total population experienced hypoglycemia leading to two patients discontinuing dulaglutide. Of these, 22 (54%) were CKD stage 4, six (15%) stage 5, 10 (24%) stage 3, and three (7%) had unspecified CKD stage (P=0.004) at the time of the hypoglycemic event. From this cohort, 11 (27%) had level 1 hypoglycemia, 13 (32%) with level 2, and 16 (39%) had hypoglycemia of an unspecified level. Importantly, one patient had level 3 hypoglycemia which required external assistance for recovery. Nearly all patients experiencing hypoglycemia had concomitant use of insulin or sulfonylureas (98%).

Finally, we evaluated clinical outcomes after the first year of dulaglutide use for the subset of the population with available data. After 1 year, for 128 patients, there was a 1.5% reduction in mean HbA1c from 8.7 ± 2.1 to 7.2 ± 1.3 (PFigure 1). Furthermore, for 131 patients, there was a 3.7 kg reduction in weight from an average of 104.4 ± 25.1 kg to 100.7 ± 23.8 kg (P