Association of Glucagon-Like Peptide-1 Receptor Agonist vs Dipeptidyl Peptidase-4 Inhibitor Use With Mortality Among Patients With Type 2 Diabetes and Advanced Chronic Kidney Disease

Chen, Jia‐Jin; Wu, Chao‐Yi; Jenq, Chang‐Chyi; Lee, Tao Han; Tsai, Chung‐Ying; Tu, Hui‐Tzu; Huang, Yu‐Tung; Yen, Chieh-Li; Yen, Tzung‐Hai; Chen, Yung‐Chang; Tian, Ya-Chung; Yang, Chih‐Wei; Yang, Huang‐Yu

doi:10.1001/jamanetworkopen.2022.1169

Cited by 31 publications

(27 citation statements)

References 61 publications

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“…We also found a signi cant reduction in all-cause death and admission due to any cause in the GLP-1RA cohort, which is compatible with a previous study on patients with ESKD [31]. Previous studies have generally emphasized admission due to heart failure, however the LEADER [9], ELIXA [32], REWIND [8], SUSTAIN-6 [10],…”

Section: Discussionsupporting

confidence: 90%

The cardiovascular and renal effects of glucagon-like peptide 1 receptor agonists in patients with advanced diabetic kidney disease

Lin

Wang

Tsai

et al. 2023

Preprint

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Background To determine whether glucagon-like peptide 1 receptor agonists (GLP-1RAs) have cardiovascular and renal protective effects in patients with advanced diabetic kidney disease (DKD) with an estimated glomerular filtration rate (eGFR) < 30 mL/min per 1.73 m2. Methods In this cohort study, patients with type 2 diabetes mellitus and eGFR < 30 mL/min per 1.73 m2 with a first prescription for GLP-1RAs or dipeptidyl peptidase 4 inhibitors (DPP-4is) from 2012 to 2021 (n=125,392) were enrolled. A Cox proportional hazard model was used to access the cardiorenal protection between the GLP-1RA and DDP-4i groups. Results A total of 8,922 participants (mean [SD] age 68.4 [11.5] years; 4,516 [50.6%] males; GLP-1RAs, n=759; DPP-4is, n=8,163) were eligible for this study. During a mean follow-up of 2.1 years, 78 (13%) and 204 (13.8%) patients developed composite cardiovascular events in the GLP-1RA and DPP-4i groups, respectively (hazard ratio [HR] 0.88, 95% confidence interval [CI] 0.68–1.13). Composite kidney events were reported in 134 (38.2%) and 393 (44.2%) patients in the GLP-1RA and DPP-4i groups, respectively (subdistribution HR 0.72, 95% CI 0.56–0.93). Conclusions GLP-1RAs had a neutral effect on the composite cardiovascular outcomes but reduced composite kidney events in the patients with advanced DKD.

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Section: Discussionsupporting

confidence: 90%

The cardiovascular and renal effects of glucagon-like peptide 1 receptor agonists in patients with advanced diabetic kidney disease

Lin

Wang

Tsai

et al. 2023

Preprint

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“…The reported benefit to all-cause mortality is of similar magnitude to an earlier retrospective cohort study of GLP-1 receptor agonist vs. DPP4I in patients with CKD stage 5 or ESKD. [29] FLOW-CHRONIC KIDNEY DISEASE TRIAL Signals from the CVOT posthoc analyses and retrospective cohort studies point to a benefit of GLP-1 agonists in patients with diabetic kidney disease and reinforce the need for a clinical trial to assess for kidney-related outcomes. The FLOW trial [30] is a randomized, placebo-controlled, double-blind parallel-group trial assessing once-weekly semaglutide injection in addition to standard of care therapy.…”

Section: Glucagon-like Peptide-1 Receptor Agonists Vs Insulinmentioning

confidence: 99%

Emerging evidence for glucagon-like peptide-1 agonists in slowing chronic kidney disease progression

Holliday,

Frost,

Navaneethan

2024

Current Opinion in Nephrology &Amp; Hypertension

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Purpose of review Diabetic kidney disease continues to increase, and several novel therapeutic agents have been shown to slow the progression of chronic kidney disease in those with diabetes. This review summarizes more recent data on the role of glucagon-like peptide-1 (GLP-1) receptor agonists and kidney outcomes. Recent findings Posthoc analysis of cardiovascular outcome trials, as well as several retrospective studies, demonstrate benefits of GLP-1 receptor agonist therapy for chronic kidney disease progression in diabetics. Although limited randomized clinical trials evidence assessing the effects of GLP-1 receptor agonists on kidney outcomes in diabetic chronic kidney disease patients have been published, FLOW-CKD trial was halted based on interim data for efficacy, and results are awaited. Summary GLP-1 receptor agonism is a promising therapy for slowing the progression of diabetic chronic kidney disease. Recent studies support kidney benefits GLP-1 receptor agonists over insulin and dipeptidyl peptidase-4-inhibitors, and the FLOW-CKD trial would inform the potential benefits for reducing the need for dialysis and kidney-disease related mortality in those with kidney disease.

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“…SGLT2i and GLP1-RA: Evidence from observational studies 10 observational studies met our inclusion criteria, with studies primarily reporting relative rather than absolute risk differences [98][99][100][101][102][103][104][105][106][107] . These studies comparing SGLT2i and GLP1-RA individually with other oral therapies (predominantly DPP4i) generally reported average relative benefits for CVD and heart failure outcomes in-line with placebo-controlled trials, with no consistent pattern of subgroup level differences across studies (Supplementary Table 1a and 1b A few observational studies compared SGLT2i and GLP1-RA CVD outcomes.…”

Section: Glp1-ra: Evidence From Clinical Trialsmentioning

confidence: 99%

Precision medicine in type 2 diabetes: A systematic review of treatment effect heterogeneity for GLP1-receptor agonists and SGLT2-inhibitors

Young

McInnes

Massey

et al. 2023

Preprint

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Background: A precision medicine approach in type 2 diabetes requires identification of clinical and biological features that are reproducibly associated with differences in clinical outcomes with specific anti-hyperglycaemic therapies. Robust evidence of such treatment effect heterogeneity could support more individualized clinical decisions on optimal type 2 diabetes therapy. Methods: We performed a pre-registered systematic review of meta-analysis studies, randomized control trials, and observational studies evaluating clinical and biological features associated with heterogenous treatment effects for SGLT2-inhibitor and GLP1-receptor agonist therapies, considering glycaemic, cardiovascular, and renal outcomes. Results: After screening 5,686 studies, we included 101 studies of SGLT2-inhibitors and 75 studies of GLP1-receptor agonists in the final systematic review. The majority of papers had methodological limitations precluding robust assessment of treatment effect heterogeneity. For glycaemic outcomes, most cohorts were observational, with multiple analyses identifying lower renal function as a predictor of lesser glycaemic response with SGLT2-inhibitors and markers of reduced insulin secretion as predictors of lesser response with GLP1-receptor agonists. For cardiovascular and renal outcomes, the majority of included studies were post-hoc analyses of randomized control trials (including meta-analysis studies) which identified limited clinically relevant treatment effect heterogeneity. Conclusions: Current evidence on treatment effect heterogeneity for SGLT2-inhibitor and GLP1-receptor agonist therapies is limited, likely reflecting the methodological limitations of published studies. Robust and appropriately powered studies are required to understand type 2 diabetes treatment effect heterogeneity and evaluate the potential for precision medicine to inform future clinical care.

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Association of Glucagon-Like Peptide-1 Receptor Agonist vs Dipeptidyl Peptidase-4 Inhibitor Use With Mortality Among Patients With Type 2 Diabetes and Advanced Chronic Kidney Disease

Cited by 31 publications

References 61 publications

The cardiovascular and renal effects of glucagon-like peptide 1 receptor agonists in patients with advanced diabetic kidney disease

The cardiovascular and renal effects of glucagon-like peptide 1 receptor agonists in patients with advanced diabetic kidney disease

Emerging evidence for glucagon-like peptide-1 agonists in slowing chronic kidney disease progression

Precision medicine in type 2 diabetes: A systematic review of treatment effect heterogeneity for GLP1-receptor agonists and SGLT2-inhibitors

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