A Possible Advantage of Glucagon-Like Peptide 1 Receptor Agonist in Kidney Transplant Recipients With Type 2 Diabetes

Abstract Diabetic kidney disease (DKD), a devastating complication of diabetes, is one of the leading causes of end stage kidney disease (ESKD). Kidney transplantation provides superior outcomes for ESKD patients with type 2 diabetes, giving opportunities to be free from dialysis, but needs lifetime immunosuppressive medications to avoid graft kidney rejection. Post-transplant hyperglycemia, however, remains to be unsolved, because immunosuppressive agents, including glucocorticoids and calcineurin inhibitors, may result in impaired insulin secretion and sensitivity. Safe and promising anti-diabetic strategy is long-awaited among kidney transplant recipients (KTRs) with type 2 diabetes. Enormous evidence has accumulated that Glucagon-like peptide 1 (GLP-1) receptor agonists have potential to maintain kidney function as well as improve glucose tolerance in patients with DKD. The present study was designed to elucidate the association between GLP-1 receptor agonist use and better graft kidney function in KTRs with type 2 diabetes. Among KTRs with type 2 diabetes between 2012 and 2019, 73 with GLP-1 receptor agonist use and 73 without GLP-1 receptor use were identified in our center. After propensity matching, 50 KTRs were newly initiated with GLP-1 receptor agonist use or other antidiabetic medications. Baseline characteristics were well-balanced in the 2 groups. KTRs with GLP-1 receptor agonist use had greater kidney function 12 months after initiation of GLP-1 receptor agonists, compared to their counterpart KTRs without GLP-1 receptor agonists, according to estimated glomerular filtration ratio (p=0.01). Interestingly, transient decrease of body mass index was observed in KTRs with GLP-1 receptor agonist use during the 12 months. All GLP-1 receptor agonist-initiated KTRs were followed up through December 31, 2019. In conclusion, GLP-1 receptor agonist treatment was associated with better graft kidney function in KTRs with type 2 diabetes. Pharmacological GLP-1 receptor activation showed favorable tolerability and may alleviate graft kidney damage in KTRs with type 2 diabetes.

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Glucagon-like peptide 1 receptor agonist (GLP-1 RA): long-term effect on kidney function in patients with type 2 diabetes

Journal of Diabetes and its Complications ◽

10.1016/j.jdiacomp.2015.04.004 ◽

2015 ◽

Vol 29 (5) ◽

pp. 670-674 ◽

Cited By ~ 36

Author(s):

Bernt Johan von Scholten ◽

Tine Willum Hansen ◽

Jens Peter Goetze ◽

Frederik Persson ◽

Peter Rossing

Keyword(s):

Type 2 Diabetes ◽

Kidney Function ◽

Receptor Agonist ◽

Term Effect ◽

Long Term Effect ◽

Glucagon Like Peptide ◽

Glucagon Like Peptide 1

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The effects of Glucagon‐like Peptide‐1 receptor agonists on kidney function and safety in type 2 diabetes

Journal of Diabetes Investigation ◽

10.1111/jdi.13552 ◽

2021 ◽

Author(s):

Min Kyung Kim ◽

Doo‐Man Kim

Keyword(s):

Type 2 Diabetes ◽

Kidney Function ◽

Receptor Agonists ◽

Glucagon Like Peptide ◽

Glucagon Like Peptide 1

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Abstract MP52: Population Health Impact of Sodium Glucose Co-Transporter 2 Inhibitors and Glucagon-Like Peptide-1 Receptor Agonists in US Adults With Type 2 Diabetes

Circulation ◽

10.1161/circ.137.suppl_1.mp52 ◽

2018 ◽

Vol 137 (suppl_1) ◽

Author(s):

Girish Nadkarni ◽

Priti Poojary ◽

Rocco Ferrandino ◽

Aparna Saha ◽

Kinsuk Chauhan ◽

...

Keyword(s):

Heart Failure ◽

Type 2 Diabetes ◽

Receptor Agonist ◽

Health Impact ◽

Complication Rates ◽

Potential Health ◽

Receptor Agonists ◽

Glucagon Like Peptide ◽

Glucagon Like Peptide 1

Introduction: Recently, sodium glucose co-transporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 (GLP-1) receptor agonists have been introduced as novel antidiabetic agents, but their potential health impact in the US is unknown. We assessed the number of potentially eligible type 2 diabetes (T2D) patients, as well as projected changes in death and complication rates for nationwide use. Methods: Based on inclusion criteria of SGLT2i and GLP-1 receptor agonist RCTs, we determined eligibility in a weighted sample of 69.2M T2D patients from 2007-2014 National Health and Nutrition Examination Survey (NHANES) data. We employed a validated microsimulation model based on the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial to simulate virtual life courses of eligible US patients. Pooled hazard ratios from meta-analyses of published RCTs were applied to model death and non-fatal adverse event rates with SGLT2i and GLP-1 receptor agonist use. Results: The proportion eligible in NHANES was 9.2% (95% CI 7.3-11.1), which translates into ~6.4M US adults. Simulated 10-year mortality (32.5%) decreased by 4.6% (95% CI 2.7-7.3) with SGLT2i and by 2.9% (95% CI 1.6-4.8) with GLP-1 receptor agonists. Mean life expectancy was 16.5 y, and increased by 1.3 y (95% CI 0.6-2.2) with SGLT2i and by 0.8 y (95% CI 0.4-1.5) with GLP-1 receptor agonists. With SGLT2i, lifetime heart failure risk decreased by 7.4% (95% CI 4.1-12.3) and end-stage renal disease (ESRD) risk decreased by 0.4% (95% CI -0.1-0.9). Improvements in these event risks were uncertain with GLP-1 receptor agonist use (Figure). With lifetime SGLT2i use, fracture risk increased from 16.9 to 22.4% (95% CI of Δ 2.5-9.6) and amputation risk rose from 5.7 to 11.2% (95% CI of Δ 2.3-9.5). Conclusions: Nationwide use of SGLT2i or GLP-1 receptor agonists may save over 8 or 5M life years, respectively. Moreover, SGLT2i may avoid over 470K new cases of heart failure and over 28K ESRD cases. Further research should illuminate whether these benefits outweigh additional costs and harms.

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Risk of Malignant Neoplasia with Glucagon-Like Peptide-1 Receptor Agonist Treatment in Patients with Type 2 Diabetes: A Meta-Analysis

Journal of Diabetes Research ◽

10.1155/2019/1534365 ◽

2019 ◽

Vol 2019 ◽

pp. 1-10

Author(s):

Yufang Liu ◽

Xiaomei Zhang ◽

Sanbao Chai ◽

Xin Zhao ◽

Linong Ji

Keyword(s):

Type 2 Diabetes ◽

Fixed Effects ◽

Receptor Agonist ◽

Meta Analysis ◽

Receptor Agonists ◽

Statistical Heterogeneity ◽

Glucagon Like Peptide ◽

Glucagon Like Peptide 1 ◽

Malignant Neoplasia

Background. Glucagon-like peptide-1 (GLP-1) receptor agonists are effective glucose-lowering drugs, but there is concern that they may increase the risk of malignant neoplasia. The present meta-analysis examined the safety of GLP-1 receptor agonists with regard to malignant neoplasia. Methods. We analyzed data from randomized controlled trials with a minimum duration of 24 weeks that assessed the incidence of neoplasms in type 2 diabetes patients receiving GLP-1 receptor agonists compared with placebo or other hypoglycemic drugs. We searched the MEDLINE, Embase, and Cochrane databases with a language restriction of English through October 1, 2018, and carried out a meta-analysis of the available trial data using a fixed effects model to calculate odds ratios (ORs) for neoplasia. Results. Thirty-four relevant articles, providing data for 50452 patients, were included in the meta-analysis. Compared with the incidence of malignant neoplasia with placebo or other interventions, no increase in malignant neoplasm formation was observed with the use of GLP-1 receptor agonists (OR 1.04, 95% confidence interval (CI) 0.94–1.15; p=0.46), liraglutide (OR 1.08, 95% CI 0.91–1.27; p=0.38), exenatide (OR 1.00, 95% CI 0.86–1.16; p=1.00), semaglutide (OR 0.89, 95% CI 0.35–2.22; p=0.80), or albiglutide (OR 1.07, 95% CI 0.23–4.88; p=0.93). A subanalysis of trials lasting longer than 3 years also showed no increase in the neoplasia risk with GLP-1 receptor agonist use (OR 1.03, 95% CI 0.92–1.15; p=0.60). Between-trial statistical heterogeneity was low for all comparisons. Conclusion. GLP-1 receptor agonists can be used without safety concerns related to malignant neoplasia in patients with type 2 diabetes.

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Effectiveness, treatment durability, and treatment costs of canagliflozin and glucagon-like peptide-1 receptor agonists in patients with type 2 diabetes in the USA

BMJ Open Diabetes Research & Care ◽

10.1136/bmjdrc-2019-000704 ◽

2019 ◽

Vol 7 (1) ◽

pp. e000704 ◽

Cited By ~ 1

Author(s):

Mukul Singhal ◽

Hiangkiat Tan ◽

Craig I Coleman ◽

Michelle Han ◽

Chi Nguyen ◽

...

Keyword(s):

Type 2 Diabetes ◽

Receptor Agonist ◽

Primary Outcome ◽

Receptor Agonists ◽

Medication Costs ◽

The Usa ◽

Glucagon Like Peptide ◽

Glucagon Like Peptide 1 ◽

Hba1c Levels

IntroductionThis real-world study compared glycemic effectiveness, treatment durability, and treatment costs with canagliflozin 300 mg versus any dose of glucagon-like peptide-1 (GLP-1) receptor agonists in patients with type 2 diabetes mellitus (T2DM) in the USA.Research design and methodsA retrospective cohort study using administrative claims and laboratory data (1 April 2012 to 28 February 2017) from the HealthCore Integrated Research Database were used to assess mean HbA1c at 3-month intervals, achievement of HbA1c thresholds (<7.0%, <8.0%, <9.0%), and treatment durability (ie, adherence, discontinuation, switching, treatment failure (ie, exceeding threshold (7.0%, 8.0%, 9.0%), having a prescription for a new antihyperglycemic agent)) in adults with T2DM who initiated canagliflozin 300 mg or any dose of a GLP-1 receptor agonist. Medication costs were calculated for adherent patients.ResultsThere were no significant differences in the primary outcome of HbA1c levels at 3-month intervals (≤12 months) in the canagliflozin 300 mg versus any dose GLP-1 receptor agonist cohort. The likelihood of achieving HbA1c<8.0% was not different (p=0.666), the likelihood of achieving HbA1c<7.0% was lower (p=0.016), and the likelihood of achieving HbA1c<9.0% was higher (p=0.020) in the canagliflozin 300 mg versus any dose GLP-1 receptor agonist cohort. The likelihood of treatment failure after reaching any HbA1c target was not different between cohorts. A higher proportion of patients were adherent to treatment (p<0.0001) and a lower proportion discontinued (p<0.0001) or switched medication (p=0.023) in the canagliflozin 300 mg versus any dose GLP-1 receptor agonist cohort. Over 1 year, medication costs were $1421 (p<0.001) lower with canagliflozin 300 mg than any dose of GLP-1 receptor agonists.ConclusionsThis real-world, US-based study found that initiation of canagliflozin 300 mg versus any dose of a GLP-1 receptor agonist in patients with T2DM was not associated with significant differences in the primary outcome of HbA1c levels at 3-month intervals for up to 12 months after index, but showed better adherence, less discontinuation, and lower drug acquisition costs compared with initiation of any dose of a GLP-1 receptor agonist.

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