Treatment of diabetes in patients undergoing organ replacement is not often studied; what are the effects of GLP-1 agonists in kidney transplants?
While glucagon-like peptide-1 (GLP-1) agonists have proven to promote glycemic control and decrease the risk of comorbidities in the general population of patients with diabetes, not many studies have focused on the efficacy and safety of GLP-1 agonist in patients who have undergone kidney transplants. Around two out of five people who have had a kidney transplant also have type 2 diabetes. One of those three who do not have diabetes pre-transplant is likely to develop diabetes after receiving a transplant. In other trials, GLP-1 agonist has been found to reduce cardiovascular and renal complications associated with diabetes by improving the estimated glomerular filtration rate (eGFR) and albuminuria. The tolerability of GLP-1 agonist is questioned due to adverse effects such as delayed gastric emptying, which can interfere with the absorption of necessary transplant medicines. This study aims to shed light on the utility of GLP-1 agonists in recipients of kidney transplants with preexisting diabetes and successional cases of diabetes.
In this retrospective cohort study based in Rochester, Minnesota, 17 recipients of kidney transplants were started on a GLP1- agonist to treat type 2 diabetes diagnosed before and after transplantation. Electronic medical records were obtained from Mayo Clinic, for the period from January 1, 2009, to May 21, 2019. Patients had to have at least one follow-up documented to be included in the trial, and patients with post-transplant diabetes mellitus were diagnosed four months after transplantation using the American Diabetes Association guidelines. Monitoring entailed age, body mass index, the reason for end-stage renal disease, sex, type of transplant and donor, immunosuppression maintenance, fasting blood glucose, HbA1c, other treatments for diabetic therapy including insulin, serum creatinine, eGFR, lipid levels, and protein in the urine. Upon initiation of the long-acting GLP-1 agonists, the subjects were observed for side effects, the reason for discontinuing the treatment, immunosuppression adjustments, and rejection of the transplanted kidney. Patients had to continue the designated therapy for a least 12 months to measure the desired outcomes.
Statistical analysis comprised median, interquartile ranges, Wilcoxon Signed Rank test for paired data, and p-values less than 0.05 were utilized to determine statistically significant results. Only 14 of the original 17 patients completed a minimum of 12 months of therapy with a GLP-1 agonist. Results showed there was no change in weight reduction. However, the use of insulin declined from a median of 63 [interquartile range 43-113] to 44 [interquartile range 25-88]. This, in turn, decreased the risk of hypoglycemia associated with insulin. None of the subjects experienced cases of acute rejection or abnormal renal function. One patient did develop acute pancreatitis that resolved upon discontinuation of the targeted drug treatment. Doses of Tacrolimus remained constant. Approximately 30% or five patients decided to stop GLP-1 agonist treatment due to adverse effects or uncontrolled blood glucose. None of the findings in the study were proven to be statistically significant. The GLP-1 agonist had no adverse impact on the transplanted organ. Gastrointestinal side effects are of considerable concern in this population due to possible potentiation with combined metformin or mycophenolate mofetil therapies.
Limitations of this study pertain to the nature of the research in that it was retrospective and contained a small number of participants. Also, the Tacrolimus levels were measured by 12-hour troughs, whereas the area under the curve is typically used to assess absorption. Future studies could examine this intervention in larger populations of organ transplant recipients, diversifying treatment regimens and their side effect profiles, and involving more well-developed endpoints. This study confirmed that the use of GLP-1 agonists could be tolerable in some recipients of kidney transplants. However, further research will be necessary to establish where GLP-1 agonists should fall in managing type 2 diabetes in patients undergoing kidney transplants.
- Patients who exceeded 12 months of GLP-1 agonist treatment experienced more significant weight loss and marked reduction in total daily insulin dosing, which lead to significantly less hypoglycemic events and ultimately controlled diabetes.
- Upon the initiation of GLP-1 agonist therapy, counseling concerning side effects and gradual dose titrations could decrease the risk of side effects and minimize unnecessary discontinuation of the treatment.
- Future studies will need to explore further whether GLP1-agonists improve the organ transplant outcomes and the patient’s overall health.
Mia Flowers, PharmD. Candidate of Florida Agricultural & Mechanical University School of Pharmacy