In type 2 diabetes, GLP-1 receptor agonists and pioglitazone had similar major liver and cardiovascular outcomes, but GLP-1 receptor agonists were linked to lower heart failure risk.
Evidence
This territory-wide target trial emulation compared 8922 new users of GLP1RA or pioglitazone and found similar risks for and major cardiovascular events, with lower heart failure risk for GLP1RA in intention-to-treat analysis.
Caveat
Because this was an observational target trial emulation, the lower heart failure signal could still reflect residual confounding despite consistent subgroup and sensitivity analyses.
Simplified
BACKGROUND: Both glucagon-like peptide 1 receptor agonist (GLP1RA) and pioglitazone are associated with cardiovascular and hepatic benefits in patients with type 2 diabetes (T2D). However, studies that directly compare their cardio-hepatic effects are lacking. We emulated a target trial to compare their effects on adverse liver and cardiovascular outcomes in T2D patients.
METHODS: We adopted an "active comparator, new user" design involving T2D patients newly prescribed GLP1RA or pioglitazone between January 2008 and December 2022. The primary outcomes were (MALO) and cardiovascular events (), with their individual outcomes and heart failure (HF) as secondary outcomes. Cox proportional hazards models were used to estimate hazard ratios (HRs) via intention-to-treat (ITT) and per-protocol (PP) analyses.
RESULTS: A total of 8922 patients (N = 4461 each group) were included. Compared to pioglitazone users, GLP1RA users had comparable risks of incident MALO (ITT: HR 0.94, 95% CI 0.66-1.34; PP: HR 1.13, 95% CI 0.60-2.15) and MACE (ITT: HR 0.99, 95% CI 0.80-1.22; PP: HR 1.10, 95% CI 0.77-1.58). The risk of HF was significantly lower in GLP1RA users in ITT analysis (HR 0.65, 95% CI 0.51-0.83). The results were consistent across most subgroup and sensitivity analyses.
CONCLUSIONS: The effects on incident major adverse liver and cardiovascular outcomes were comparable between GLP1RA and pioglitazone, although the risk of incident HF was lower with GLP1RA. Treatment decisions for T2D patients at risk of adverse cardio-hepatic events should be individualized, considering HF risk and the need for weight loss, which if present, GLP1RA may be preferred.
Key numbers
0.94
Risk of ()
Hazard ratio in intention-to-treat analysis.
0.99
Risk of ()
Hazard ratio in intention-to-treat analysis.
0.65
Lower Risk of Heart Failure
Hazard ratio in intention-to-treat analysis.
Full Text
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Declarations. Ethics approval and consent to participate: The study protocol was approved by the Ethics Committee of the Institutional Review Board of the University of Hong Kong/Hospital Authority Hong Kong West Cluster (Reference Number: UW 15-613). Informed consent was not required as all data was anonymous. Consent for publication: Not applicable. Competing interests: C.H.L received advisory board and lecture honorarium from AstraZeneca, Bayer, Boehringer Ingelheim, Echosens, Eli Lilly, Gilead, GSK, Novo Nordisk and Sanofi Aventis. C.K.H.W and X.X were supported by the AIR@InnoHK administered by Innovation and Technology Commission, Government of Hong Kong Special Administrative Region, China.
