Diabetes Mellitus in Kidney Transplant Recipients and New Hypoglycemic Agent Options
Abstract
1. Introduction
2. Prevalence and Diagnosis of PTDM
3. Risk Factors for PTDM
4. Treatment for PTDM
5. Novel Hypoglycemic Agents
5.1. Sodium Glucose Co-Transporter Type 2 Inhibitors
Number of Patients | Time from Transplant | Intervention | Primary Endpoints | State | |
---|---|---|---|---|---|
Effect of Adding Dapagliflozin to Allograft Dysfunction of Renal Transplanted Patients [69] | 211 KTRs | 1–5 years | Dapaglifozin 10 mg vs. placebo | Effect on renal function | Completed |
Efficacy, Mechanisms and Safety of SGLT2 Inhibitors in Kidney Transplant Recipients (INFINITI2019) [64] | 52 KTRs T2DM–PTDM | ≥6 months | Dapaglifozin 10 mg vs. placebo | Reduced Blood pressure | Completed |
Empagliflozin Treatment in Kidney Transplant Recipients (SEKTR) [66] | Veterans KTRs T2DM–PTDM | ≥3 months | Empaglifozin 12.5 mg | Safety and efficacy | Recruiting |
CardioRenal Effects of SGLT2 Inhibition in Kidney Transplant Recipients (CREST-KT) [63] | 72 KTRs | 12–60 months | Empaglifozin 10 mg vs. placebo | Safety and efficacy | Recruiting |
The Efficacy, Mechanism & Safety of Sodium Glucose Co-Transporter-2 Inhibitor & Glucagon-Like Peptide 1 Receptor Agonist Combination Therapy in Kidney Transplant Recipients (HALLMARK) [68] | 20 KTRs T2DM–PTDM | ≥3 months | Dapaglifozin 10 mg plus semaglutide 1.0 mg/mL | Short-term efficacy and safety (12 weeks) | Recruiting |
Can Dapagliflozin Preserve Structure and Function in Transplanted Kidneys? (DEAKTransplant) [71] | 330 KTRs | ≥6 weeks | Dapaglifozin 10 mg vs. placebo | Effect on eGFR slope; Effect on graft fibrosis and proteomic; Effect on metabolic risk | Recruiting |
The RENAL LIFECYCLE Trial: A RCT to Assess the Effect of Dapagliflozin on Renal and Cardiovascular Outcomes in Patients With Severe CKD [67] | 1500 severe CKD pts | Not specified | Dapaglifozin 10 mg vs. placebo | Reno- and cardio protective efficacy and safety | Recruiting |
Effect of Empagliflozin vs Linagliptin on Glycemic Outcomes, Renal Outcomes & Body Composition in Renal Transplant Recipients With Diabetes Mellitus (EmLinaRenal) [70] | KTRs T2DM–PTDM | ≥3 months | Empaglifozin 25 mg vs. linagliptin 5 mg | Effect on glycaemic outcomes; Effect on renal outcomes; Effect on body composition | Recruiting |
Effects of Empagliflozin in Reducing Oxidative Stress After Kidney Transplantation [73] |
40 KTRs T2 DM | Not specified | Empaglifozin 25 mg plus insulin vs. insulin | Effect on oxidative stress | Recruiting |
SGLT2i in Diabetic Patients with Renal Transplantation [65] |
72 KTRs PTDM | ≥3 months | SGLT2i | Safety and efficacy | Active, not recruiting |
Acute Effects of SGLT2 Inhibitor on Kidney Allograft Oxygen Tension (SGL-TX-MR) [72] |
8 KTRs No DM | ≥6 months | 50 mg empaglifozin single dose vs. placebo | Change in kidney allograft cortical and medullary oxygen tension | Recruiting |
5.2. Glucagon-like Peptide-1 Receptor Agonists
6. Nonsteroidal Mineralocorticoid Receptor Antagonist: Finerenone
7. Conclusions
Author Contributions
Funding
Conflicts of Interest
Abbreviations
KT | Kidney transplantation |
ESKD | End-stage kidney disease |
DM | Diabetes mellitus |
KDIGO | Kidney Disease: Improving Global Outcomes |
KTRs | Kidney transplant recipients |
CKD | Chronic kidney disease |
NODAT | New-onset diabetes mellitus after transplantation |
PTDM | Post-transplantation diabetes mellitus |
HbA1c | Hemoglobin A1c |
OGTT | Oral glucose tolerance test |
IGT | Impaired glucose tolerance |
CV | Cardiovascular |
ADA | American Diabetes Association |
FPG | Fasting glucose sample |
2HPG | 2 hr plasma glucose |
RPG | Random plasma glucose |
MM | Mismatching |
CNIs | Calcineurin inhibitors |
mTORi | Mammalian target of rapamycin inhibitor |
MMF | Mycophenolate mofetil |
SGLT2is | Sodium glucose co-transporter type 2 inhibitors |
GLP1RAs | Glucagon-like peptide-1 receptor agonists |
Ns-MRA | Nonsteroidal mineralocorticoid receptor antagonist |
HF | Heart failure |
FDA | Food and Drug Administration |
BMI | Body mass index |
AKI | Acute kidney injury |
AEs | Adverse events |
UTIs | Urinary tract infections |
DKA | Diabetic ketoacidosis |
eGFR | Estimated glomerular filtration rate |
RCT | Randomized clinical trial |
MACEs | Major adverse cardiac events |
MAKEs | Major adverse kidney events |
GIPR | Glucose-dependent insulinotropic polypeptide receptor |
TNF-α | Tumor necrosis factor alpha |
GI | Gastrointestinal |
FAERS | Food and Drug Administration adverse event reporting system |
AIN | Acute interstitial nephritis |
USRDS | US Renal Data System |
RASi | Renin–angiotensin system inhibitor |
CYP | Cytochrome |
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Normal Glucose Tolerance | Prediabetes | Diabetes Mellitus |
---|---|---|
FPG < 100 mg/dL | FPG 100−125 mg/dL | Symptoms of diabetes |
2-h PG < 140 mg/dL | 2-h PG during 75-g OGTT 7.8−11.0 mmol/L | RPG ≥ 200 mg/dL |
HbA1c < 5.7% (< 39 mmol/mol) | HbA1c 5.7−6.4% (39−47 mmol/mol) | FPG ≥ 126 mg/dL |
2-h PG ≥ 200 mg/dL during 75-g OGTT | ||
HbA1c ≥6.5%(>47 mol/mol) |
Study | Population | Intervention | Included Criteria | Primary Endpoints | Results |
---|---|---|---|---|---|
AlKindi et al. [54] | 8 KTRS | SGLT2i | T2DM/PTDM Stable renal function | Safety and efficacy | Improvement in HbA1c and body weight Safety |
Halden et al. [55] | 49 KTRS | Empagliflozin | PTDM Transplanted >1 year Stable renal function Stable immunosuppressive therapy | Safety and efficacy | Improvement in HbA1c and body weight Safety |
Mahling et al. [56] | 10 KTRs | Empagliflozin | T2DM/PTDM Stable graft function No recurrent UTIs | Efficacy, safety, and effect on allograft function | Stable graft function Reduced HbA1c, body weight, BP Safety |
Schwaiger et al. [57] | 14 KTRs | Empagliflozin | PTDM Insulin therapy < 40 IU/d HbA1c <8.5% eGFR >30 mL/min/1.72 m2 Transplanted > 6 months | Withdrawing insulin | Empagliflozin safe as add-on therapy |
Song et al. [58] | 50 KTRs | SGLT2i | T2DM/PTDM eGFR > 30 mL/min/1.72 m2 None AKI ≤ 30 days None UTIs 6 months | Changes in weight, insulin dosage, HgbA1C, magnesium concentration and safety outcomes | Improvement in weight, hypomagnesemia and insulin usage |
Lim et al. [59] | 226 KTRs | SGLT2i | T2DM/PTDM SGLT2i treatment > 90 d | Primary composite outcome: all-cause mortality, death-censored graft failure (DCGF), and serum creatinine doubling | Lower risk of primary composite outcome |
Sánchez Fructuoso et al. [60] | 339 KTRS | SGLT2i | T2DM/PTDM | Safety profile | UTIs 14% Risk factors: prior episode and female sex |
Sheu et al. [61] | 1970 KTRS | SGLT2i | T2DM/PTDM For SGLT2i users group, administered SGLT2i within the 3 months post-transplant | All-cause mortality MACE MAKE | Reduced all-cause mortality, MACE, MAKE |
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Bartoli, G.; Dello Strologo, A.; Arena, M.; Ceravolo, M.J.; Mitterhofer, A.P.; Pesce, F.; Grandaliano, G. Diabetes Mellitus in Kidney Transplant Recipients and New Hypoglycemic Agent Options. Int. J. Mol. Sci. 2025, 26, 5952. https://doi.org/10.3390/ijms26135952
Bartoli G, Dello Strologo A, Arena M, Ceravolo MJ, Mitterhofer AP, Pesce F, Grandaliano G. Diabetes Mellitus in Kidney Transplant Recipients and New Hypoglycemic Agent Options. International Journal of Molecular Sciences. 2025; 26(13):5952. https://doi.org/10.3390/ijms26135952
Chicago/Turabian StyleBartoli, Giulia, Andrea Dello Strologo, Maria Arena, Maria Josè Ceravolo, Anna Paola Mitterhofer, Francesco Pesce, and Giuseppe Grandaliano. 2025. "Diabetes Mellitus in Kidney Transplant Recipients and New Hypoglycemic Agent Options" International Journal of Molecular Sciences 26, no. 13: 5952. https://doi.org/10.3390/ijms26135952
APA StyleBartoli, G., Dello Strologo, A., Arena, M., Ceravolo, M. J., Mitterhofer, A. P., Pesce, F., & Grandaliano, G. (2025). Diabetes Mellitus in Kidney Transplant Recipients and New Hypoglycemic Agent Options. International Journal of Molecular Sciences, 26(13), 5952. https://doi.org/10.3390/ijms26135952