Effects of GLP-1 receptor agonists and SGLT-2 inhibitors in heart transplant patients with type 2 diabetes: Initial report from a cardiometabolic center of excellence

doi:10.1016/j.healun.2021.02.012

The Journal of Heart and Lung Transplantation

Volume 40, Issue 6, June 2021, Pages 426-429

https://doi.org/10.1016/j.healun.2021.02.012 Get rights and content

Type 2 diabetes mellitus (T2D) is a common comorbidity among patients who have undergone heart transplantation. Recently two classes of glucose-lowering medications (sodium-glucose cotransporter type-2 inhibitors [SGLT-2Is] and glucagon-like-peptide-1 receptor agonists [GLP-1RAs]), have been shown to significantly improve cardiovascular outcomes. There is a paucity of data regarding their use in immunosuppressed patients, with many studies specifically excluding this population. We retrospectively evaluated the safety and efficacy of GLP-1RAs and SGLT-2Is in patients who had undergone orthotopic heart transplant at a high-volume center. Among 21 patients, we found significant weight loss, reductions in insulin use, hemoglobin A1c, and low-density lipoprotein-cholesterol. Moreover, both SGLT-2Is and GLP-1RAs were well tolerated with no adverse events leading to discontinuation of either therapy. While larger studies of patients after solid organ transplant are needed, this small hypothesis-generating study demonstrates that SGLT-2Is and GLP-1RAs appear safe and effective therapies among patients with T2D after heart transplant.

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Source of funding: No financial support was received.

Dr. Nassif declares modest speaking honoraria from Abbott. Dr. Thomas is supported by the National Heart, Lung, and Blood Institutes of Health under award number T32HL110837. Dr. O'Keefe is on the speaker's bureau for Amgen, AstraZeneca, Boehringer Ingelheim, Procter/Gamble, and Sanofi. Dr. Kosiborod has served on Clinical Trial Steering/Executive/Publications committees for and/or received honoraria/served on the advisory board or as a

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Cited by (13)

The International Society for Heart and Lung Transplantation (ISHLT) guidelines for the care of heart transplant recipients
2023, Journal of Heart and Lung Transplantation
Longitudinal Change and Predictors of Myocardial Flow Reserve by Positron Emission Tomography for the Evaluation of Cardiac Allograft Vasculopathy Following Heart Transplantation
2023, Journal of Cardiac Failure
Positron emission tomography (PET) myocardial flow reserve (MFR) is a noninvasive method of detecting cardiac allograft vasculopathy in recipients of heart transplants (HTs). There are limited data on longitudinal change and predictors of MFR following HT.
We conducted a retrospective analysis of HT recipients undergoing PET myocardial perfusion imaging at an academic center. Multivariable linear and Cox regression models were constructed to identify longitudinal trends, predictors and the prognostic value of MFR after HT.
Of HT recipients, 183 underwent 658 PET studies. The average MFR was 2.34 ± 0.70. MFR initially increased during the first 3 years following HT (+ 0.12 per year; P = 0.01) before beginning to decline at an annual rate of -0.06 per year (P < 0.001). MFR declines preceding acute rejection and improves after treatment. Treatment with mammalian target of rapamycin (mTOR) inhibitors (37.2%) slowed the rate of annual MFR decline (P = 0.03). Higher-intensity statin therapy was associated with improved MFR. Longer time post-transplant (P < 0.001), hypertension (P < 0.001), chronic kidney disease (P < 0.001), diabetes mellitus (P = 0.038), antibody-mediated rejection (P = 0.040), and cytomegalovirus infection (P = 0.034) were associated with reduced MFR. Reduced MFR (HR: 7.6, 95% CI: 4.4–13.4; P < 0.001) and PET-defined ischemia (HR: 2.3, 95% CI: 1.4–3.9; P < 0.001) were associated with a higher risk of the composite outcome of mortality, retransplantation, heart failure hospitalization, acute coronary syndrome, or revascularization.
MFR declines after the third post-transplant year and is prognostic for cardiovascular events. Cardiometabolic risk-factor modification and treatment with higher-intensity statin therapy and mechanistic target of rapamycin inhibitors are associated with a higher MFR.
Use of sodium-glucose co-transporter 2 inhibitors in solid organ transplant recipients with pre-existing type 2 or post-transplantation diabetes mellitus: A systematic review
2023, Transplantation Reviews
Citation Excerpt :
As such, sick day management education and plan should be implemented to prevent diabetic ketoacidosis in patients who are receiving SGLT2 inhibitors [42]. This review was limited by a paucity of data, and studies were restricted to kidney and heart transplant recipients [2,3,5,7,29–41]. Available trials were heterogeneous in study design, type and duration of diabetes, and duration post-transplant.
Sodium-Glucose Co-Transporter 2 (SGLT2) inhibitors have demonstrated kidney, cardiovascular and mortality benefits in the general population; however, the evidence is limited in solid organ transplant recipients. The aim of this systematic review was to evaluate the current efficacy and safety data of SGLT2 inhibitors in adult kidney, heart, lung, and liver transplant recipients with pre-existing type 2 or post-transplantation diabetes mellitus.
We searched MEDLINE, MEDLINE Epub, CENTRAL, CDSR, EMBASE, CINAHL, and sources of unpublished literature. All primary interventional and observational studies on SGLT2 inhibitors in transplant recipients were included. Clinical outcomes included mortality, cardiovascular and kidney events, and adverse events such as graft rejection. Surrogate markers including hemoglobin A1c (HbA1c) and weight reduction were also evaluated.
Of the 17 studies that were included in this systematic review, there were 15 studies on kidney transplant recipients (n = 2417 patients) and two studies on heart transplant recipients (n = 122 patients). There was only one randomized controlled trial which evaluated 49 kidney transplant patients over 24 weeks. Overall, studies were heterogeneous in study design, sample size, duration of diabetes, time to SGLT2 inhibitor initiation post-transplantation (ranging from 0.88 to 11 years post kidney transplant; five to 5.7 years post heart transplant) and follow-up (ranging from 0.4 to 5.25 years in kidney transplant patients; 0.75 to one year in heart transplant patients). Only one retrospective study evaluated mortality as a part of a composite outcome in kidney transplant patients; however, study limitations restrict generalizability of results. Overall, studies could not confirm clinical cardiovascular and kidney benefits in the transplant population. Findings suggested that SGLT2 inhibitors may improve glycemic control; however, they are associated with urinary tract infection. Diabetic ketoacidosis and acute kidney injury also occurred in these studies, with precipitating factors such as infection and acute heart failure exacerbation.
While SGLT2 inhibitors are promising agents with expanding indications in the non-transplant population, these agents may not be suitable for all solid organ transplant recipients, and close monitoring (e.g. for urinary tract infections) and patient education (e.g. sick day management) are essential if these agents are initiated. Evidence is based on short-term findings and suggests an association with hemoglobin A1c reduction and increased adverse events. Further long-term randomized controlled trials are needed to evaluate the effect of SGLT2 inhibitors on clinically important outcomes, including mortality reduction, in solid organ transplant recipients.
Post-transplant diabetes mellitus following heart transplantation
2022, Journal of Heart and Lung Transplantation
Citation Excerpt :
Similarly, use of vildagliptin (a dipeptidyl peptidase-4 inhibitor that increases GLP-1) following heart transplant was found to be effective in reducing hemoglobin A1C without significant safety concerns.51 A report of 21 heart transplant recipients treated with an SGLT-2 inhibitor and/or GLP-1 receptor agonist reported weight loss, reduction in insulin use, hemoglobin A1C, and LDL without significant adverse effects requiring drug discontinuation.52 In addition to the beneficial effects of SGLT-2 inhibitors for PTDM, their benefits may extend to treatment of anemia which is common following heart transplant, affecting up to 47% of recipients.53
Post-transplant diabetes mellitus (PTDM) is common following heart transplant, impacting greater than 20% of patients with most cases occurring in the first year after transplant. PTDM is associated with multiple negative sequelae including increased post-operative infections, a higher rate of renal failure, and increased mortality. Compared with pre-transplant diabetes mellitus, PTDM has several unique risk factors and immunosuppressive medications play an important role in disease pathophysiology. Newer treatments for hyperglycemia, including glucagon like peptide-1 receptor agonists and sodium glucose cotransporter-2 inhibitors, may counter the mechanisms of immunosuppression-related hyperglycemia making them an appealing treatment option for patients with PTDM. Here, we review the definitions, incidence, risk factors, pathophysiology, clinical outcomes, treatment options, pharmacologic considerations, and future directions in PTDM.
Safety and effects of SGLT-2 inhibitor use among LVAD patients with type 2 diabetes mellitus
2022, American Heart Journal Plus: Cardiology Research and Practice
SGLT-2 inhibitors have been shown to confer reduced risk of adverse cardiovascular events in patients with heart failure, and have also been studied preliminarily among heart transplant patients, with overall positive findings. Use of SGLT-2 inhibitors among patients with durable mechanical circulatory support has not been studied. Here we present our results from a combined retrospective cohort of LVAD patients on SGLT-2 inhibitors at two major academic centers, which showed a good safety profile but prompted questions for further investigation. We advocate for further research into the safety and impact of SGLT-2 inhibitors among LVAD patients.
Diagnosis and treatment of post‑transplant diabetes mellitus
2024, Chinese Journal of Diabetes Mellitus

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^⁎: Drs. Sammour and Nassif contributed equally to this work and served as co-first authors.

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Brief CommunicationEffects of GLP-1 receptor agonists and SGLT-2 inhibitors in heart transplant patients with type 2 diabetes: Initial report from a cardiometabolic center of excellence

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Acknowledgments

J Heat Lung Transplant

J Heat Lung Transplant

Brief Communication
Effects of GLP-1 receptor agonists and SGLT-2 inhibitors in heart transplant patients with type 2 diabetes: Initial report from a cardiometabolic center of excellence