Study shows benefits of GLP-1 drugs for kidney transplant recipients with type 2 diabetes

Kidney transplant recipients with type 2 diabetes treated with a new class of anti-obesity drugs were less likely to experience organ failure and survived longer, a new study shows. Not only is obesity a known risk factor for diabetes, but it also increases risk of postsurgical complications, such as inflammation, organ rejection, and early death.

Previous research had suggested some benefit for kidney transplant recipients with a history of type 2 diabetes who took the medications, originally designed to treat diabetes, at some point after their transplant and then experienced slower declines in kidney function than those who did not. These GLP-1 agonists include semaglutide, liraglutide, and dulaglutide, now marketed as Ozempic, Wegovy, Saxenda, Victoza, and Trulicity.

It remained unclear, however, whether physicians should prescribe the drugs, given their known side effects, which include inflammation in the pancreas and liver problems. There had also been concern that GLP-1 agonists might increase the risk for a rare form of thyroid cancer in patients already taking immune-suppressing drugs to prevent transplant rejection, a condition where the body's immune system attacks the transplanted kidney as it would a foreign virus or bacteria.

Led by researchers at NYU Langone Health, the new study showed that those who were prescribed GLP-1 agonists, mostly within three years of receiving their transplant, were 49% less likely to experience organ failure - when the transplanted kidney stops functioning, and the patient has to resume dialysis - than those who had not been prescribed a GLP-1. Kidney transplant recipients taking the medications also had a 31% reduced risk of dying within five years of their starting on the medication, compared to those who did not take the drugs.

While risk for inflammation in the pancreas, liver problems, or thyroid cancer was not found to be higher in the patients with diabetes treated with GLP-1s, the study did show the treated group had a 49% greater chance of developing diabetic retinopathy. This potentially blinding damage to the light-sensitive tissue lining the back of the eyes often accompanies diabetes when blood sugar levels are not under control.

Our study results are the strongest evidence to date that GLP-1 agonist drugs are largely safe and effective tools for addressing type 2 diabetes in kidney transplant recipients."

Babak Orandi, MD, PhD, study lead investigator, transplant surgeon, and obesity medicine specialist

"Our research offers a large amount of real-world clinical data to guide the management of benefits and risks of GLP-1 use in kidney transplant recipients," said Orandi, an associate professor in the Departments of Surgery and Medicine at NYU Grossman School of Medicine.

Publishing in the journal The Lancet Diabetes and Endocrinology online March 5, the study was designed to clarify the value and safety of the drugs. Researchers reviewed the medical records of 18,016 kidney transplant recipients with pretransplant diabetes in the United States between 2013 and 2020, of whom 1,916 were prescribed GLP-1s.

"Our findings also show that while the benefits of GLP-1 drugs are significant, their use does come with some added risk of diabetic retinopathy, suggesting that physicians need to carefully monitor the eye health of kidney transplant recipients with diabetes who are started on these drugs," said study senior investigator and epidemiologist Mara McAdams-DeMarco, PhD. McAdams-Demarco is an associate professor in the Departments of Surgery and Population Health at NYU Grossman School of Medicine.

People with diabetes lose the ability to produce or efficiently use insulin, the hormone produced by the pancreas and needed to regulate the body's blood sugar and energy levels. Because diabetic retinopathy, the leading cause of blindness in the United States, can occur in people whose blood sugar levels are corrected too quickly, Orandi says the key to managing its risk is to screen for diabetic retinopathy, particularly in people with uncontrolled diabetes, and make sure that blood sugar levels are under control prior to taking GLP-1s. He also suggests slowly adjusting GLP-1 doses from small to large (titrating) in kidney transplant recipients with severe diabetes or in patients with a history of eye problems.

Among the study's other findings was that GLP-1 users were more likely to be younger, female, Black, and poor than those who were not prescribed the medications.

For the study, researchers used data from the U.S. Renal Data System, which integrates data from the Organ Procurement and Transplantation Network that allocates organ transplantation across North America, the U.S. Centers for Medicare and Medicaid Services, and Medicare claims data, including information on prescription drug use.

More research is needed, the researchers say, into the biological mechanisms behind GLP-1 agonists and how they improve kidney health posttransplant.

Type 2 diabetes is among the leading causes of end-stage kidney disease, the primary cause for a quarter-million Americans now awaiting a kidney transplant.

Funding for the study was provided by National Institutes of Health grants R01AG077888, K02AG076883, R01DK114074, R01DK120518, K01DK132490, and K24AI144954.

Besides Orandi and McAdams-DeMarco, other NYU researchers involved in this study are Yui Chen, MHS; Yiting Li, MPH; Garyn Metoyer, MD; Michael Weintraub, MD; Sunjae Bae, MD, PhD; Nicole Ali, MD; Bonnie Lonzo, MD; Christine Ren-Fielding, MD; Holly Lofton, MD; Akash Gujral, MS; and Dorry Segev, MD. Another study co-investigator is Krista Lentine, MD, at Saint Louis University in Missouri.

Orandi has served on an advisory board for Boehringer Ingelheim. Lofton has served on advisory boards and/or received research funding and speaking fees from Novo Nordisk, Eli Lilly, and Currax.

McAdams-DeMarco has received speaking fees from Chiesi.

Segev has served as a consultant for and/or received speaking fees from pharmaceutical and healthcare companies AstraZeneca, Behring, CareDx, CSL, Jazz Pharmaceuticals, Mallinckrodt, Novavax, Novartis, Optum Health Education, Sanofi, Thermo-Fisher Scientific, Transmedics, and Veloxis.

None of these groups were involved in the current study. The terms and conditions of all of these relationships are being managed in accordance with the policies and procedures of NYU Langone Health.