Evaluating GLP-1 Receptor Agonists and SGLT2 Inhibitors in Kidney Transplant Recipients with Diabetes

In a real-world cohort of 141 kidney transplant recipients, GLP-1 receptor agonists and SGLT2 inhibitors produced mean weight loss of −3.38 kg and a BMI reduction of −1.28 kg/m2 (both p < 0.001) over a mean treatment exposure of 2.4 years, with parallel improvements in lipid measures and systolic blood pressure.

This single-center, retrospective longitudinal cohort screened 183 patients and included 141 adults who started therapy between August 2013 and April 2024: 52 had pre-existing type 2 diabetes (T2DM) and 89 developed post-transplant diabetes mellitus (PTDM). Inclusion required age ≥18 years, confirmed diabetes, and continued use of a GLP-1 RA and/or SGLT2i at last follow-up.

Primary endpoints were changes in metabolic control (weight, BMI, HbA1c, lipids, blood pressure) and transplant-specific renal indicators (eGFR, serum creatinine). The observational, single-center design supports real-world relevance but limits causal inference and broad generalizability.

Efficacy signals were consistent for cardiometabolic endpoints: mean body-weight fell by −3.38 kg and BMI by −1.28 kg/m2 (both p < 0.001), with accompanying reductions in total cholesterol and LDL‑c and a significant decrease in systolic blood pressure. Glycemic control varied by subgroup: overall HbA1c declined non-significantly by −0.31% (p = 0.21), while the pre-existing T2DM subgroup experienced a significant HbA1c reduction (−0.50%, p < 0.01). In contrast, the PTDM subgroup showed a rise in fasting plasma glucose (112.62 to 125.01 mg/dL, p = 0.03), underscoring differential glucose responses by diabetes timing.

Safety signals were manageable. Urinary tract infections occurred in 18% (26/141), most asymptomatic or mild; one moderate UTI prompted discontinuation. Nausea affected 6% (9/141) and accounted for most tolerability-related stops; GLP-1 RA therapy was discontinued in seven patients mainly because of potential drug–drug interaction concerns. Hypoglycemia was recorded in 9% (12/141), and all events were asymptomatic or mild.

There were no cases of urosepsis, euglycemic ketoacidosis, acute rejection, severe hypoglycemia, or treatment-related death. These data support focused monitoring for genitourinary infections and gastrointestinal tolerability during therapy.

Renal indicators remained stable over the mean 2.4-year exposure: no significant changes in eGFR or serum creatinine were observed, proteinuria did not increase on average, and no acute rejection events were reported—together supporting preserved renal allograft function across this cohort.

Clinical implications are straightforward: appropriate candidates are stable kidney transplant recipients with diabetes who need weight reduction and cardiometabolic risk lowering. Implementation should emphasize careful patient selection, medication reconciliation to avoid interactions, and protocolized follow-up with routine urinary symptom checks/urine testing, assessment of gastrointestinal tolerability, and serial eGFR/creatinine monitoring during the initial years of therapy. These pragmatic steps balance benefit and safety while informing future prospective evaluation.

Key Takeaways:

• GLP-1 RAs and SGLT2is in 141 transplant recipients produced mean weight loss of −3.38 kg and BMI −1.28 kg/m2 with improved lipids and systolic blood pressure.
• Glycemic benefit was significant in pre-existing T2DM (HbA1c −0.50%, p < 0.01) but not across the entire cohort; PTDM showed an increase in fasting glucose.
• Renal function remained stable with no acute rejection events; main safety concerns were mostly mild UTIs (18%) and transient nausea (6%).