Scientific reportsOct 6, 2025

Safety signals of GLP-1 receptor agonists combined with metformin based on FDA reports

GLP-1 Therapies Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Jun 27, 2026

Abstract

Essence

FAERS reports linked GLP-1 receptor agonist plus metformin therapy to common gastrointestinal and weight-loss events, unexpected kidney and pancreatic cancer signals, and demographic-specific adverse-event patterns.

Evidence

This retrospective used 48,214 FAERS reports from 2004-2024 and compared combination therapy with GLP-1 receptor agonist or metformin monotherapy using ROR and BCPNN sensitivity analysis.

Caveat

FAERS disproportionality data can detect reporting signals but cannot prove incidence, causality, or that combination therapy is clinically safer than monotherapy.

Simplified

This study analyzed adverse events (AEs) of GLP-1RA and metformin combination therapy using FAERS data (2004-2024). A retrospective was conducted using the reporting odds ratio (ROR) on FAERS data (2004-2024), with Bayesian confidence propagation neural network (BCPNN) employed for sensitivity analysis. Adverse reactions were compared between combination therapy and monotherapy (GLP-1 RAs or metformin alone), followed by stratified analyses by gender, age, and body weight. Among 48,214 reports (57.5% female), common AEs included nausea and weight loss. Unexpected signals included kidney injury and pancreatic cancer. Monotherapy showed higher AE rates. Males reported more renal calculi and early-onset AEs (≤ 30 days), while females had delayed AEs (> 360 days). Weight loss was consistent across all demographics. The combination therapy of GLP-1 receptor agonists and metformin demonstrates superior safety over monotherapy, while revealing novel adverse events and demographic-specific risk patterns, thereby offering reliable evidence to inform clinical practice.

Key numbers

=6.71

Reduction in Lactic Acidosis Incidence

Compared to monotherapy cases (15,789).

=1.62

Acute Kidney Injury Incidence

Compared to 7694 cases in monotherapy.

n=9651

Nausea Reports

Reported cases in combination therapy.

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Funding

Competing interests

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authors report competing interests

6 report none

PubMed

Safety signals of GLP-1 receptor agonists combined with metformin based on FDA reports

Abstract

Key numbers

Full Text

Funding

Competing interests

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Abstract

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Competing interests

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