Is there data for or against use of GLP-1 agonists in solid organ transplant patients? Do GLP-1 agonists increase the risk for rejection?

Comment by InpharmD Researcher

Limited retrospective studies suggest that GLP-1 receptor agonists (GLP-1RAs) can be safe and effective for the treatment of current type-2 diabetes mellitus (T2DM) and preventing post-transplant DM in solid organ transplant patients while also potentially improving kidney graft survival. However, most of the studies are focused on kidney transplant patients. While data is still preliminary, the results do not suggest an increased risk for solid organ rejection.

Background

A 2022 review discusses the use of glucagon-like-peptide-1 receptor agonists (GLP-1 RAs) in individuals with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD). Although GLP-1 RAs are known for their effectiveness in controlling blood sugar levels, promoting weight loss, and reducing the risk of hypoglycemia, they are underutilized in this specific patient population. Notably, at the time of publication of this review, there were no prospective clinical trials that have comprehensively assessed the effectiveness, safety, and tolerability of GLP-1 RAs in patients with both T2DM and stage 5 CKD who are either undergoing dialysis or have received a kidney transplant. However, retrospective studies have suggested that GLP-1 RAs may be safe and effective for kidney transplant recipients with T2DM, and that GLP-1 RAs do not significantly impact renal function or transplant outcomes in kidney transplant recipients with pre- or post-transplant diabetes. Additional retrospective studies involving T2DM patients with kidney transplants who were treated with GLP-1 RAs observed improved glucose control and weight loss, with renal function remaining stable during a mean follow-up period of 12 months (Table 1). In a small study of seven patients, improvements in renal function and reductions in hemoglobin A1c (HbA1c) levels and weight were noted after an average follow-up period of 19.4 ± 7.6 months. Moreover, a retrospective chart review involving patients with T2DM and solid organ transplants (81% kidney transplants), revealed that treatment with dulaglutide resulted in sustained reductions in weight, body mass index (BMI), and insulin use over a 24-month period, with no increased risk of graft failure, cardiovascular issues, or all-cause mortality (Table 3). These findings suggest that GLP-1 RAs may potentially be a viable treatment option for patients with T2DM post-kidney transplant; however, further research is warranted to assess their impact on patient survival. [1]

A 2021 narrative review investigated the role of GLP-1 RAs and sodium-glucose cotransporter-2 inhibitors (SGLT-2i) in the prevention and management of T2DM in solid organ transplant (SOT) patients. The weight loss and improved beta-cell survival conferred by GLP-1 RAs can theoretically prevent or delay the onset of post-transplant DM. Additionally, calcineurin inhibitor toxicity has been linked to the pathogenesis of post-transplant DM, which GLP-1 RAs have demonstrated a protective effect against. However, clinical evidence remains sparse and limited to small retrospective or observational studies with short-to-medium follow-up periods. Of the GLP-1 RAs, dulaglutide and liraglutide are usually the primary agents investigated, and most often researched within the realm of kidney transplants. These preliminary studies suggest that GLP-1 RAs are safe and effective in post-transplant patients, aside from GI-related intolerance, which has led to reports of discontinuation rates up to 30%. An additional concern is the reduced delayed gastric emptying by GLP-1 RAs that could potentially modify the absorption of immunosuppressive agents, such as tacrolimus. However, the authors are not aware of any clinical data for this interaction. [2]

A 2023 letter to the editor describes a retrospective clinical study of 23 patients investigating the use of GLP1-RAs for renal transplant patients with diabetes in the United Kingdom. Patients included must have been on GLP1-RAs for at least 12 months after transplantation. The duration of follow-up was 26.5 ± 16.5 months. At year 1, there was a significant reduction in HbA1c levels (-1.3% ± 1.5%; p= 0.003) along with a non-significant reduction in weight (-2.66 ± 5.82 kg; p= 0.08). However, the weight reduction in the 12 remaining patients at 2-year follow-up was significant (-4.73 ± 5.29 kg; p= 0.02). There were no changes in renal function or proteinuria. A comparison between dulaglutide and liraglutide does not suggest a significant difference in metabolic and biochemical parameters. A small patient population, retrospective design, and minimal background information limit the findings of the study. [3]

Another 2022 letter to the editor describes a retrospective study of 50 kidney transplant patients who received GLP-1RA with a follow-up of 6 or 12 months. Patients were prescribed semaglutide, liraglutide, or dulaglutide in addition to their maintenance immunosuppressive regimen. Improvement in eGFR was only seen at 12 months of follow-up (+3.5 mL/min/1.73 m2; p= 0.03), but HbA1c significantly decreased at six months (-9 mmol/mol; p<0.001). Urine albumin-to-creatinine ratio, body mass index, and daily insulin dose also decreased significantly at six months. Twelve patients (24%) developed side effects, primarily nausea and vomiting, which improved after dose reductions. Two patients (4%) discontinued treatment and are not stated to be directly related to treatment. [4]

A 2018 review states there are no clinical trials on the use of GLP-1 agonists in patients with post-liver transplant diabetes mellitus (PLTDM). One case series of five kidney transplant recipients with post-transplant diabetes reported the safety of liraglutide administered for 21 days, without changes in tacrolimus levels. There is still insufficient evidence about the impact of newer families of antidiabetics (GLP-1 agonists, SGLT-2 inhibitors), and their effect on immunosuppressive drugs has not completely been clarified. For long-term PLTDM outpatient management, there is scarce evidence to support the choice of one antidiabetic agent over another. [5], [6]

References:

[1] Górriz JL, Romera I, Cobo A, O'Brien PD, Merino-Torres JF. Glucagon-Like Peptide-1 Receptor Agonist Use in People Living with Type 2 Diabetes Mellitus and Chronic Kidney Disease: A Narrative Review of the Key Evidence with Practical Considerations. Diabetes Ther. 2022;13(3):389-421. doi:10.1007/s13300-021-01198-5
[2] Ertuglu LA, Porrini E, Hornum M, et al. Glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter 2 inhibitors for diabetes after solid organ transplantation. Transpl Int. 2021;34(8):1341-1359. doi:10.1111/tri.13883
[3] Mallik R, Ali O, Casabar M, et al. Glucagon-like peptide-1 receptor analogues in renal transplant recipients with diabetes: Medium term follow of patients from a single UK centre. Diabet Med. 2023;40(5):e15057. doi:10.1111/dme.15057
[4] Vigara LA, Villanego F, Orellana C, et al. Effectiveness and safety of glucagon-like peptide-1 receptor agonist in a cohort of kidney transplant recipients. Clin Transplant. 2022;36(5):e14633. doi:10.1111/ctr.14633
[5] Peláez-Jaramillo MJ, Cárdenas-Mojica AA, Gaete PV, Mendivil CO. Post-Liver Transplantation Diabetes Mellitus: A Review of Relevance and Approach to Treatment. Diabetes Ther. 2018;9(2):521-543. doi:10.1007/s13300-018-0374-8
[6] Burra P, Becchetti C, Germani G. NAFLD and liver transplantation: Disease burden, current management and future challenges. JHEP Rep. 2020;2(6):100192. Published 2020 Oct 9. doi:10.1016/j.jhepr.2020.100192
Literature Review

A search of the published medical literature revealed 5 studies investigating the researchable question:

Is there data for or against use of GLP-1 agonists in solid organ transplant patients? Do GLP-1 agonists increase the risk for rejection?

Level of evidence

C - Multiple studies with limitations or conflicting results  Read more→


Please see Tables 1-5 for your response.

 

A Retrospective Study of Glucagon-Like Peptide 1 Receptor Agonists for the Management of Diabetes After Transplantation

Design

Retrospective, single-center, cohort study

N=19

Objective

To evaluate the safety and efficacy of glucagon-like peptide 1 receptor agonists (GLP-1RAs) in the management of diabetes after transplantation

Study Groups

 Transplant patients (n=19)

Inclusion Criteria

Patients who underwent kidney, heart, or liver transplantation; had either pre-existing type 2 diabetes mellitus (T2DM) or developed post-transplant diabetes mellitus (PTDM), were subsequently treated with any of the available GLP-1RAs (exenatide, liraglutide, dulaglutide, or semaglutide)

Exclusion Criteria

 <19 years old, patients with type 1 diabetes mellitus (T1DM), used a GLP-1RA for less than 3 months

Methods

This was a retrospective cohort study from one center in Nebraska. Patients who underwent kidney, heart, or liver transplantation and were treated with a GLP-1 agonist for diabetes were evaluated.

The providers started their patients on a titrated GLP-1RA dose per the recommended protocol; some patients did not reach the maximum dose. 

Duration

 Patients were followed for at least 12 months

Outcome Measures

 Change from baseline in weight, renal function, and A1c

Baseline Characteristics

  

Transplant patients (n=19)

Age, years (range)

 62 (48-71)

Female

7 (36.8%)

Organ transplanted

Kidney

Liver

Heart

 

7 (36.8%)

7 (36.8%)

5 (26.3%)

Body mass index, kg/m2 (range)

 35.98 (26.96–46.78)

A1c, % (range)

 8.0 (4.6–10.8)

Diabetes medications

Insulin

Metformin

DPP4i

SGLT2i

Sulfonylurea

 

17 (89.5%)

3 (16.8%)

3 (16.8%)

2 (10.5%)

2 (10.5%)

Tacrolimus used

18 (94.7%)

Results

  

Transplant patients (n=19)

Change in BMI, kg/m2 (95% CI)

After 3 months

After 6 months

After 12 months

 

-0.89 (-1.44 to -0.33)

-1.07 (-1.85 to -0.29)

-1.63 (-2.53 to -0.73)

Change in A1c, % (95% CI)

After 3 months

After 6 months

After 12 months

 

-1.08 (-1.65 to -0.51)

-0.96 (-1.68 to -0.25)

-0.75 (-1.55 to 0.05)

Change in estimated GFR, mL/min/1.73 m2 (95% CI)

After 3 months

After 6 months

After 12 months

 

-0.19 (-3.55 to 3.18)

1.38 (-0.76 to 3.51)

1.08 (-1.63 to 3.80)

After 12 months, there were no significant changes in tacrolimus levels in the 18 patients who were taking the medicaiton.

Adverse Events

Nausea (26.3%)

Study Author Conclusions

This data suggest that GLP-1 receptor agonists do not affect tacrolimus levels or transplant outcomes in solid organ transplant (SOT) recipients in the short term. GLP-1 agonists also seem to be as effective in SOT recipients for glycemic control and weight loss as in the non-transplant population with diabetes.

InpharmD Researcher Critique

This study is limited by its retrospective nature and lack of a control group. In addition, the baseline values are single measurements prior to the start of GLP-1 agonist, which may not reflect the true status prior to GLP-1 agonist start. The heterogenous transplant type could have resulted in different effects on glucose metabolism; however, this cohort was on a stable immunosuppressive regimen and GLP-1 agonist therapy was started after a mean of 60 months after the transplant.



References:

Thangavelu T, Lyden E, Shivaswamy V. A Retrospective Study of Glucagon-Like Peptide 1 Receptor Agonists for the Management of Diabetes After Transplantation. Diabetes Ther. 2020;11(4):987-994. doi:10.1007/s13300-020-00786-1

 

Long-Acting Glucagon-Like Peptide-1 (GLP-1) Agonist Therapy in Post Solid Organ Transplant Patients

Design

Retrospective, observational cohort study

N=20

Objective

To evaluate the use of glucagon-like peptide (GLP-1) agonists for the management of diabetes and weight gain in post-transplant recipients with preexisting type 2 diabetes mellitus (T2DM) or new-onset diabetes after transplant (NODAT)

Study Groups

 Transplant patients (n=20)

Inclusion Criteria

 Transplant recipients; preexisting T2DM or NODAT; managed with insulin, oral agents, or both prior to initiating a GLP-1 agonist

Exclusion Criteria

None reported

Methods

This was a retrospective cohort study of transplant patients at a single center in Texas. Data was collected from 1-25 months after the start of GLP-1 therapy. The GLP-1 agonists used were liraglutide or exenatide.

Duration

 Follow-up: 12 months

Outcome Measures

 Changes in A1c, weight, serum creatinine, and tacrolimus levels

Baseline Characteristics

  

Transplant patients (n=20)

Organ transplanted

Kidney

Lung

Heart

Liver

Multi-organ

 

7 (35%)

1 (5%)

6 (30%)

3 (15%)

3 (15%)

Concurrent medications

Corticosteroids

Tacrolimus

Cyclosporine

Sirolimus

 

20 (100%)

15 (75%)

3 (15%)

1 (5%)

Results

  

Transplant patients (n=20)

A1c, %

Baseline

Change after 3 months

Change after 6 months

Change after 12 months

 

7 ± 1.8

-0.25 ± 1.19

-0.58 ± 1.58

-0.02 ± 2.0 (-4.1 to +3.2)

Weight, lbs

Baseline

Change after 3 months

Change after 6 months

Change after 12 months

 

241 ± 41

-6.5 ± 6.8

-12 ± 8.5

-16 ± 7.6 (-26.8 to -4)

Serum creatinine, mg/dL

Baseline

Change after 3 months

Change after 6 months

Change after 12 months

 

1.3 ± 0.5

-0.08 ± 0.26

-0.03 ± 0.3

-0.06 ± 0.4

Tacrolimus levels (FK506), ng/mL

Baseline

Change after 3 months

Change after 6 months

Change after 12 months

 

8.2 ± 2.9

-0.98 ± 5.2

-1.1 ± 3.4

+0.2 ± 2.6

Adverse Events

Not studied

Study Author Conclusions

In patients with T2DM or NODAT, GLP-1 agonist therapy results in weight reduction as well as a reduction in HgbA1c, without adverse effects on immunosuppressive drug levels or creatinine. Further investigation is warranted to evaluate the safety, efficacy and long-term outcomes.

InpharmD Researcher Critique

This study was presented as a poster abstract, so the methods and baseline characteristics were not fully presented. This study is limited by its retrospective design and small sample size.



References:

Krisl J, Gaber A, Sadhu A. Long-Acting Glucagon-Like Peptide-1 (GLP-1) Agonist Therapy in Post Solid Organ Transplant Patients. Transplantation. 2014;98:523-4. doi:10.1097/00007890-201407151-01757

 

Largest single-centre experience of dulaglutide for management of diabetes mellitus in solid organ transplant recipients

Design

Retrospective chart review

N= 63

Objective

To analyze the efficacy and safety of dulaglutide in the management of type-2 diabetes in solid organ transplant (SOT) recipients

Study Groups

All subjects (n= 63)

Inclusion Criteria

Age above 18 years, history of any SOT, follow-up of more than 6 months with dulaglutide

Exclusion Criteria

History (personal or familial) of medullary or thyroid C-cell carcinoma, pancreatitis, multiple endocrine neoplasia syndrome types-2 or severe gastrointestinal (GI) disease

Methods

Data was collected at baseline and at 6, 12, and 24 months. Patients initiated dulaglutide at a dose of 0.75 mg once weekly, and the dose was increased as clinically indicated to a maximum of 1.5 mg once weekly.

Duration

Treatment: October 30, 2014 to January 1, 2018

Follow-up: 2 years

Outcome Measures

Primary: change in weight, BMI, insulin requirements, cardiovascular morbidity, graft survival, and all-cause mortality

Secondary: glycosylated hemoglobin (HbA1c), renal function, estimated GFR (eGFR), and liver function tests 

Baseline Characteristics

  

All subjects (n = 63)

 

  

Age, years

 58     

Male

 68%    

Patients per race/ethnicity

White

Black

Hispanic

Other

 

71%

23%

5%

1%

    

Type of organ transplant

Kidney

Liver

Liver-kidney

Heart

 

81%

16%

1.5%

1.5%

    

Immunosuppression based on drug class

CNI

CCI

mTOR inhibitors

Maintenance steroid

Belatacept

Steroid used for rejection

 

81%

57%

54%

21%

3%

22% 

    
Time since transplant, months (range) 47.8 (7.8-330)    
Patients with family history of diabetes 65%    

Patients with PTDM onset based on timing since transplant

< 1 month

1-12 months

> 12 months

 

86%

9%

5%

    
BMI, kg/m2 (range) 32.5 (22.9-49.3)    
Creatinine, mg/dL (range) 1.55 (0.8-3.4)    

Patients based on CKD stages

CKD 1

CKD 2

CKD 3a

CKD 3b

CKD 4

CKD 5 and ESRD

 

1.5%

25.6%

22.2%

30.15%

20.6%

0

    
History of cardiovascular disease before GLP-1 RA (angina, non-fatal MI, stroke, CHF) 33%    

Abbreviations: BMI, body mass index; CCI, cell cycle inhibitors (myfortic, mycophenolate or imuran); CHF, congestive heart failure; CKD, chronic kidney disease; CNI, calcineurin inhibitors (cyclosporine, tacrolimus); MI, myocardial infarction; mTOR inhibitor, mammalian target of rapamycin (sirolimus, everolimus); PTDM, post-transplant diabetes mellitus

Results

Endpoint

6 mo post GLP-1 RA (n= 59)

12 mo post GLP-1 RA (n= 49)

24 mo post GLP-1 RA (n= 13)

Mean of paired difference for weight, kg

 2.07 (baseline weight, 98.71; p< 0.003)  4.01 (baseline weight, 100.15; p< 0.001) 5.23 (baseline weight, 99.5; p< 0.03) 

Mean of paired difference for BMI, kg/m2

 0.81 (baseline BMI, 32.85; p< 0.001) 1.35 (baseline BMI, 33.3; p< 0.005) 2.01 (baseline BMI, 32.97; p< 0.04) 

Mean of paired difference for HbA1c

 0.75 (baseline HbA1c, 7.59%; p< 0.001) 0.41 (baseline HbA1c, 7.62%; p= 0.07) 0.64 (baseline HbA1c, 7.64%; p= 0.23)
Mean of paired difference for creatinine 0.09 (baseline creatinine, 1.73; p= 0.05) 0.01 (baseline creatinine, 1.64; p= 0.87) 0.18 (baseline creatinine, 1.8; p= 0.14)
Mean of paired difference for eGFR −2.4 (baseline eGFR, 47.13; p= 0.09) 0.14 (baseline eGFR, 48.35; p= 0.93) −6.54 (baseline eGFR, 42.38; p= 0.07)
Percentage graft survival 100% 98.2% 98.2%
Mean of paired difference for insulin pre and post-treatment 5.94 units (p= 0.0002) -- --

Percentage of patient's insulin requirements

Decreased insulin need

Unchanged insulin need

Increased insulin need

 

47.3%

40%

12.2%

 -- --

Mortality at end of follow-up

3% (one patient, sepsis; other, cardiac arrest)

 -- --
Cardiovascular morbidity (angina, non-fatal MI, revascularization, stroke, CHF) 1.5% (one patient, angina) --  -- 
Abbreviations: BMI, body mass index; CHF, congestive heart failure; eGFR, estimated glomerular filtration rate; GLP -1, glucagon-like peptide; HbA1c, glycosylated hemoglobin A1c; MI, myocardial infarction

The mean daily insulin requirement before dulaglutide treatment was 22.9 units, which decreased to a mean of 17.03 units after dulaglutide treatment (mean of paired difference, 5.95 units; p= 0.0002).

After dulaglutide treatment, 13% of patients were able to discontinue the use of all other diabetes medications.

None of the patients experienced transaminitis during the study period.

Adverse Events

Non-severe hypoglycaemic event: 6.3%, none experienced severe hypoglycemia that required hospitalization

Other GI manifestations documented in 1.5%-3% of patients: nausea, vomiting, diarrhea or abdominal pain

No increase in the incidence of pancreatitis, gallstones, or thyroid cancer. One patient developed post-transplant lymphoproliferative disorder (PTLD), which is thought to be unrelated to dulaglutide.

Study Author Conclusions

Despite its retrospective design, our study is the first, large, real-world experience of the efficacy, safety and patient tolerability of dulaglutide in SOT and is thus noteworthy. The beneficial effect persisted during 2 years of follow-up, suggesting it as a valuable long-term treatment option. Further large-scale, prospective trials are warranted, to analyse the effect of dulaglutide on diabetes-related microvascular and macrovascular complications in SOT.

InpharmD Researcher Critique

The study primarily included Caucasian males, potentially impacting the applicability of the results. Moreover, biases could arise due to a relatively small sample size and a retrospective, non-blinded design.



References:

Singh P, Pesavento TE, Washburn K, Walsh D, Meng S. Largest single-centre experience of dulaglutide for management of diabetes mellitus in solid organ transplant recipients. Diabetes Obes Metab. 2019;21(4):1061-1065. doi:10.1111/dom.13619

 

Possible Advantage of Glucagon-Like Peptide 1 Receptor Agonists for Kidney Transplant Recipients With Type 2 Diabetes 

Design

Retrospective cohort study

N= 146

Objective

To elucidate the possible protective effects of glucagon-like peptide 1 receptor agonists (GLP-1 RAs) on kidney graft function after successful kidney transplantation (KTX)

Study Groups

GLP-1 RA (n= 73)

Non-GPL-1 RA (n=73)

Inclusion Criteria

 All KTX patients with type 2 diabetes mellitus (T2DM), either used or did not use GLP1-RAs (liraglutide, dulaglutide, exenatide, or lixisenatide) for at least 24 months

Exclusion Criteria

 Type 1 diabetes, transferred to other hospitals before the follow-up period of 24 months

Methods

Follow-up of patient data commenced when KTX patients had stable kidney graft function which continued until kidney graft failure, death, SGLT2 inhibitor use, or the end date of December 31, 2020. Maintenance immunosuppressive regimens consisted of triple therapy with a calcineurin inhibitor, corticosteroid, and antiproliferative agents. Dose adjustments of immunosuppressive agents were performed based on pharmacokinetic properties.

Duration

Data collection period: January 2012 to December 2018

Follow-up: 24 months

Outcome Measures

 Primary: sustained estimated glomerular filtration rate (eGFR) reduction of at least 40% from baseline for 4 months post-transplantation

Baseline Characteristics

  

GLP-1 RA (n= 73)

Non-GP-1 RA (n=73)

  

Age, years 

 59.7 ± 10.1 55.0 ± 10.5  

Female

27.4% 34.2%  

Body mass index, kg/m2 

 23.1 ± 3.06 27.0 ± 3.96  

eGFR, mL/min/1.73m2 

 46.9 ± 12.7 41.8 ± 14.4  

HbA1c 

 6.7% ± 0.80% 7.47% ± 1.3%  

Immunosuppressive agent

Calcineurin inhibitor

Antiproliferative agents

 

100%

100%

 

100%

100%

  

Prednisone 5 mg/day

 100% 100%  

Results

Endpoint

GLP-1 RA (n= 73)

Non-GP-1 RA (n=73)

Odds ratio (p-Value)

Sustained eGFR reduction of at least 40%

1

6

0.105 (< 0.05)

Adverse Events

 N/A

Study Author Conclusions

 GLP-1 RAs resulted in lower eGFR reduction compared with non–GLP-1 RAs and may contribute to better kidney graft survival after KTX.

InpharmD Researcher Critique

The small population size prevented analysis of the individual effects of each GLP-1 RA on eGFR and hindered the detection of improvements in kidney function. Subclinical chronic rejection could have influenced long-term kidney graft.



References:

Sato T, Azuma Y, Ozone C, et al. Possible Advantage of Glucagon-Like Peptide 1 Receptor Agonists for Kidney Transplant Recipients With Type 2 Diabetes. J Clin Endocrinol Metab. 2023;108(10):2597-2603. doi:10.1210/clinem/dgad177

 

Single-center Evaluation of Safety & Efficacy of Glucagon-Like Peptide-1 Receptor Agonists in Solid Organ Transplantation

Design

Retrospective chart review

N= 118

Objective

To assess the safety and efficacy of glucagonlike peptide-1 receptor agonists (GLP-1 RAs) in a larger cohort of solid organ transplant recipients with type 2 diabetes mellitus (T2DM)

Study Groups

Recipient cohort (N= 118)

Inclusion Criteria

Age ≥18 years; history of living or deceased donor transplant with pre-existing T2DM or post-transplant diabetes mellitus (DM); receipt of GLP-1 RA agent for ≥ 3 months; Hemoglobin A1c (HbA1c) level drawn between 3 and 12 months after GLP-1 RA initiation

Exclusion Criteria

No documented follow-up visit after 3-months of GLP-1 RA therapy, documented nonadherence to GLP-1 RA, duration of use < 3 months or unknown initiation date

Methods

Chart reviews were performed in a medical center affiliated with a transplant center. A matched pair analysis was completed to compare outcomes from baseline to post-GLP-1 RA initiation.

Duration

Follow-up: January 2018 to April 2021

Outcome Measures

Change from baseline to 3 to 12 month nadir of HbA1c, fasting blood glucose (FBG), weight, and renal effects; change in total daily dose of insulin, achievement of a HbA1c < 7.5%

Baseline Characteristics

  

Recipient cohort (N= 118)

  

Age, years

 58 ± 11  

Weight, kg

 86.7 ± 19.12  

BMI, kg/m2

 31.5 ± 5.69  

Female

59%  

Hispanic

 72.9%  

GLP-1 RA use

Duration of therapy, days

Time from transplant to initiation, days (IQR)

 

201 ± 140

1,029 (480-2,365)

  

Type of transplant

Kidney

Lung

Liver

 

70.3%

6.8%

19.5%

  

Previous history

Transplant

Pre-transplant DM

Underlying GI disease

Myocardial infarction

Stroke

Heart failure

 

11.9%

67.8%

19.5%

4.2%

4.2%

9.3%

  

GLP-1 RA agent

Liraglutide

Dulaglutide

Semaglutide

Exenatide ER

 

30.5%

38.1%

27.1%

4.2%

  

Abbreviations: BMI, body mass index; ER, extended release; GI, gastrointestinal; IQR, interquartile range

Four patients received combined transplants; three received kidney-liver, and one received kidney-pancreas.

Results

Median endpoint

Recipient cohort (N= 118)

p-value

HbA1c % (IQR)

 -0.8 (-0.2 to -1.7) <0.0001

FBG, mg/dL (IQR)

 -20 (-3 to -53) <0.0001

Serum creatinine, mg/dL (IQR)

 -0.09 (-0.01 to -0.23) <0.0001

eGFR, mL/min (IQR)

 5 (0 to 13) <0.0001

Body weight, kg

 -0.2 ± 16 <0.0001

BMI, kg/m2

 -0.5 ± 4.5 0.0008

Efficacy outcomes are shown as median change from baseline to 3 to 12-month nadir.

Achievement of HbA1c < 7.5% was accomplished in 31 patients (26.2%) at baseline and 54 patients (45.8%) at follow-up.

The median baseline daily insulin requirement was 26.5 (IQR 0-66) units and 34 (IQR 0–72) at the last follow-up within 12 months of GLP-1 RA initiation; no significant change was found in daily insulin requirements.

Adverse Events

Common Adverse Events: nausea/vomiting in 12 patients (10%), diarrhea in 4 patients (3.4%), pancreatitis in 5 patients (4.2%), at least one hypoglycemic event in 9 patients (7.1%)

Serious Adverse Events: transplant rejection in 3 patients (2.5%), graft dysfunction in 1 patient (1%), transaminitis in 1 patient (1%); the episodes of rejection and graft dysfunction were deemed unlikely by investigators to be due to GLP-1 RA use. No patient had myocardial infarction, 1 patient had stroke, and 3 patients were diagnosed with heart failure by the 12-month follow-up

Percentage that Discontinued due to Adverse Events: 2 patients

Study Author Conclusions

This was the largest evaluation evaluating the use of GLP1-RA, demonstrating the use of GLP1-RA in solid organ transplant was both safe and effective. Given GLP1-RA agents have demonstrated hyperglycemic, cardiovascular, and weight loss benefits in non-transplant patients, evaluation of these agents in transplant recipients would be important.

InpharmD Researcher Critique

Safety data was limited to provider documentation in notes, and so the incidence of adverse events may be underreported. Conclusions drawn from this data may not be generalizable to a population outside of kidney transplant recipients due to the volume included, despite the inclusion of other organ transplants.



References:

Sweiss H, Hall R, Zeilmann D, et al. Single-center Evaluation of Safety & Efficacy of Glucagon-Like Peptide-1 Receptor Agonists in Solid Organ Transplantation. Prog Transplant. 2022;32(4):357-362. doi:10.1177/15269248221122867