Single-center Evaluation of Safety & Efficacy of Glucagon-Like Peptide-1 Receptor Agonists in Solid Organ Transplantation

Abstract

Introduction: Given the negative outcomes associated with uncontrolled diabetes mellitus, non-insulin therapies with glycemic, cardiovascular, and weight-loss benefits in the general population, such as the glucagonlike peptide-1 receptor agonists (GLP1-RA) have become a more alluring therapeutic option in transplant populations. However, limited evidence exists to demonstrate its safety and efficacy in solid organ transplant. Methods: This program evaluation included adult kidney, liver, lung transplant recipients initiated on a GLP1-RA for diabetes mellitus management for a minimum of 3 months, had at least one follow-up visit after starting therapy, and had at least one hemoglobin A1c (HbA1c) level drawn between 3–12 months after GLP1-RA initiation. Outcomes were assessed at time of initiation of GLP1-RA (baseline) and 3–12 months post-initiation. Nadir values between 3–12 months were utilized to assess outcomes. Results: One-hundred eighteen patients met study inclusion criteria. Seventy-percent of patients received a kidney transplant, 19.5% received a liver transplant, and 6.8% received a lung transplant. A statistically significant difference was observed in median fasting blood glucose and HbA1c at baseline to 3–12-month nadir (P < 0.0001). A significant weight loss benefit was also observed. The rate of adverse drug reactions was low. Seven-percent of patients experienced nausea, 4.2% developed pancreatitis, and 7.1% reported having had at least one hypoglycemic event. Discussion: This is the largest study evaluating GLP1-RA in organ transplantation and demonstrates GLP1-RA is both safe and effective. Further assessment on long-term use of these agents on cardiovascular and renal outcomes is still needed.

Sweet and simple as syrup: A review and guidance for use of novel antihyperglycemic agents for post‐transplant diabetes mellitus and type 2 diabetes mellitus after kidney transplantation

“…and Sweiss et al. observed pancreatitis in 5.9% and 4.2% of their study cohorts, respectively 52,55 . Since many studies excluded patients who did not continue GLP1RA therapy, the rates for drug discontinuation cannot be accurately assessed from the available literature.…”

“…whose study cohort had poorly controlled T2DM at baseline 57 . Variable weight loss of .2–9.9 kg was observed in seven studies with no significant changes in the remaining two studies 50–53,55–58 . Since diabetic nephropathy is a progressive disease, it was not possible to assess renoprotective effects of GLP1RA without adequate control arms.…”

“…Since diabetic nephropathy is a progressive disease, it was not possible to assess renoprotective effects of GLP1RA without adequate control arms. In eight studies that included eGFR, either no significant changes or slight improvements from baseline were reported 50–53,55–58 . Of note, no study reported worsening eGFR on GLP1RA therapy.…”

“…Putting these together, the impact of GLP1RA on tacrolimus levels seems minimal and manageable by therapeutic drug monitoring. Rejection episodes and patient deaths were reported in two studies; however, the authors did not comment on the association with GLP1RA therapy 50,52 …”

“…Among seven studies that included timing of GLP1RA initiation, the median/mean times from transplant to the initiation of GLP1RA were ≥2 years in six studies, and the earliest time to initiation was mean of 11 months post-transplant. [50][51][52][53][54][55][56] The duration of follow-up ranged from 3 months to 24 months.…”