Using Sitagliptin as a Treatment to Prevent New Onset Diabetes After Kidney Transplantation

New-onset diabetes after transplantation (NODAT) is a complication of solid organ
transplantation. In the University of Nebraska Medical Center (UNMC) Kidney-Pancreas
Transplant Clinic, the frequency of this complication exceeds 50% of kidney transplant
recipients without diabetes prior to transplantation. NODAT is associated with increased
morbidity and mortality. As this complication appears to occur rather soon after
transplantation, potential preventative strategies need to be instituted soon after
transplantation. Although traditional risk factors, such as family history, obesity, and
minority status, explain some of the additional risk, it is thought that the
immunosuppressive agents themselves are responsible for the increased risk of NODAT. The
immunosuppressive agents are needed to prevent rejection, and we are left to consider
additional strategies to prevent the onset of NODAT. We propose to conduct a pilot study
utilizing the dipeptidyl peptidase-4 inhibitor, sitagliptin, in a randomized, double-blinded,
placebo-controlled study in consecutive kidney transplant recipients at the University of
Nebraska Medical Center. We have tested sitagliptin in patients with type 2 diabetes who have
received a kidney transplant and have shown no major side effects or alterations in
immunosuppressive drug levels. This agent is FDA-approved for the treatment of type 2
diabetes, but it has a low rate of hypoglycemia. It is thought to work by inhibiting the
enzyme that naturally breaks down glucagons-like peptide-1 (GLP-1), thus increasing
endogenous levels of GLP-1. GLP-1 inhibits glucagons and has stimulatory effects on beta cell
function. Although the current study will treat all non-diabetic patients in the hope that
NODAT is delayed or prevented, this incretin-based therapy is thought to have a low risk for
hypoglycemia and other side effects. In addition, it can be safely used during low-GFR
conditions. The study will attempt to recruit 40 subjects (20 sitagliptin and 20 control
subjects). Patients will initiate placebo or control at 2 weeks after transplantation.
Subjects will be followed in the UNMC Transplant Clinic. Initially, patients will be seen
weekly and later will be followed every three months for up to 1 year. The primary outcome is
the development of NODAT based on the 2003 Consensus International Guidelines. Fasting
glucose levels will be followed according to usual post-transplant monitoring with testing as
frequently as weekly during the recent post-transplant period and eventually going to at
least monthly. Secondary outcomes include HbA1c values and glucose, insulin, C-peptide, and
proinsulin levels after a 75 oral glucose load that will be obtained at baseline and then
every three months. In addition, we will follow side effects, including hypoglycemia. The
study will have a local Data Safety Monitoring Board (DSMB). Consent will be obtained prior
to transplantation.

Inclusion Criteria:

- Recipient of a kidney transplant at UNMC, including cadaveric or living donor
transplant.

Exclusion Criteria:

- A previous diagnosis of diabetes or previous criteria for diabetes, according to the
American Diabetes Association, not previously recognized as diabetes.

- Simultaneous transplant of another solid organ, such liver or heart.

- Patient unable to take oral medication.

- Patient unable to give informed consent.

- Hypersensitivity to sitagliptin.