GLP-1 receptor agonists (GLP-1RA) are associated with a significantly lower incidence of (0.8 vs. 1.7 per 1,000 person-years).
Compared to dipeptidyl peptidase-4 inhibitors (DPP-4i), GLP-1RA showed a reduced incidence of cirrhosis (29.3 vs. 32.9 per 1,000 person-years).
The incidence of (CVD) was lower with GLP-1RA (57.2 vs. 73.9 per 1,000 person-years).
(CKD) occurred less frequently in the GLP-1RA group (4.5 vs. 6.8 per 1,000 person-years).
GLP-1RA was linked to a lower incidence of non-liver cancer (16.9 vs. 22.9 per 1,000 person-years).
Significant inverse associations for these outcomes persisted in the per-protocol analysis, with hazard ratios ranging from 0.60 to 0.77.
Simplified
BACKGROUND/AIMS: Information about the association of glucagon-like peptide-1 receptor (GLP-1RA) with liver and non-liver complications is insufficient in patients with type 2 diabetes (T2D) and metabolic dysfunction-associated steatotic liver disease (MASLD). We conducted a target trial emulation study to evaluate whether GLP-1RA decreases the risk of liver and non-liver outcomes.
METHODS: Patients with T2D and MASLD initiating GLP-1RA or dipeptidyl peptidase-4 inhibitor (DPP-4i) were included from 2013 to 2022 in Merative™ Marketscan® Research Databases. Primary outcomes included incidences of (1) (HCC) and cirrhosis, and (2) (CVD), (CKD), and non-liver cancer. Inverse probability of treatment weighting was applied to balance baseline characteristics and Cox regression models were conducted to estimate hazard ratio (HR) and 95% confidence interval (CI).
RESULTS: In the intention-to-treat design, GLP-1RA, compared with DPP-4i, had a significantly lower incidence (per 1,000 person-years) of HCC (0.8 vs. 1.7; HR 0.53, 95% CI 0.39-0.71), of cirrhosis (29.3 vs. 32.9; HR 0.91, 95% CI 0.86-0.96), of CVD (57.2 vs. 73.9; HR 0.90, 95% CI 0.86-0.95), of CKD (4.5 vs. 6.8; HR 0.73, 95% CI 0.64-0.84), and of non-liver cancer (16.9 vs. 22.9; HR 0.82, 95% CI 0.77-0.89). In the per-protocol design, significant inverse associations for these study outcomes still were observed, with HR 0.60-0.77.
CONCLUSION: In this emulated target trial of nationwide patients with T2D and MASLD, GLP-1RA use, when compared with DPP-4i, was associated with a significantly lower risk of liver and non-liver complications.
Key numbers
0.8 vs. 1.7 per 1,000 person-years
Lower incidence of
Incidence rates for GLP-1RA vs. DPP-4i users.
57.2 vs. 73.9 per 1,000 person-years
Lower incidence of
Incidence rates for GLP-1RA vs. DPP-4i users.
4.5 vs. 6.8 per 1,000 person-years
Lower incidence of
Incidence rates for GLP-1RA vs. DPP-4i users.
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Conflicts of Interest . MHN received research grants via Stanford University from Pfizer, Enanta, Astra Zeneca, GSK, Delfi, Innogen, Exact Science, CurveBio, Gilead, Vir Biotech, Helio Health, National Cancer Institute, Glycotest and personal fees from consulting/advisory board from Intercept, Exact Science, Gilead, GSK. MFY received research funding from Assembly Biosciences, Arrowhead Pharmaceuticals, Bristol Myer Squibb, Fujirebio Incorporation, Gilead Sciences, Merck Sharp and Dohme, Springbank Pharmaceuticals, Sysmex Corporation, Roche, and is an advisory board member and/or received research funding from AbbVie, Aligos therarpeutics, Arbutus Biopharma, Bristol Myer Squibb, Dicerna Pharmaceuticals, Finch Therapeutics, GlaxoSmithKline, Gilead Sciences, Janssen, Merck Sharp and Dohme, Clear B Therapeutics, Springbank Pharmaceuticals, Roche. WKS received speaker’s fees and is an advisory board member of Abbott, received research funding from Alexion Pharmaceuticals, Boehringer Ingelheim, Pfizer and Ribo Life Science, received speaker’s fees and received research funding from AstraZeneca, and is an advisory board member, received speaker’s fees and researching funding from Gilead Sciences. The other authors have nothing to disclose.
