GLP-1 Receptor Agonists Show Potential as Tools Against Chronic Inflammation in Diabetes

Recent clinical evidence is transforming the understanding of glucagon-like peptide-1 receptor agonists (GLP-1 RAs), suggesting these agents offer therapeutic benefits that extend far beyond glycemic control and weight loss. A comprehensive systematic review and meta-analysis published in PeerJ shows that GLP-1 RAs play a role in modulating metabolic inflammation, a chronic low-grade state that drives the progression of type 2 diabetes and its vascular complications.¹

For pharmacists on the frontlines of diabetes management, these findings provide a robust mechanistic rationale for the cardiovascular and multiorgan protection observed in large-scale clinical trials.¹

About the Meta-Analysis

The PeerJ analysis, which synthesized data from 25 randomized controlled trials, found that GLP-1 RA treatment leads to significant reductions in key inflammatory biomarkers, specifically C-reactive protein (CRP) and tumor necrosis factor-alpha (TNF-α).¹

These results are echoed and expanded upon by a larger meta-analysis of over 6,000 patients in Frontiers in Endocrinology, which confirmed that GLP-1 RAs significantly lower CRP levels compared to both placebo and other oral antidiabetic drugs. Although the impact on IL-6 has remained inconsistent across various studies, the consistent suppression of CRP and TNF-α suggests a clear anti-inflammatory signature for this drug class.^1,2

The clinical relevance of these findings is particularly high for pharmacists monitoring patients with high cardiovascular risk. Systemic mediators like CRP and TNF-α are not merely markers of disease but active contributors to endothelial dysfunction, plaque instability, and atherogenesis.^1,2

The PeerJ study highlights that the anti-inflammatory efficacy of these medications is influenced by both the specific agent used and the duration of therapy, with more pronounced improvements observed in patients who remain on treatment for 36 weeks or longer. Subgroup data suggest that long-acting agents, such as dulaglutide, may provide more substantial reductions in inflammatory markers compared to short-acting alternatives, likely due to more sustained receptor activation.¹

The Role of the Pharmacist in GLP-1 Education

Understanding the dual nature of these anti-inflammatory effects is essential for pharmacist-led patient education. The benefits appear to stem from both indirect and direct pathways. Indirectly, GLP-1 RAs reduce inflammation by improving glucose levels and promoting weight loss, which decreases the production of advanced glycation end products and reduces proinflammatory cytokine secretion from visceral adipose tissue.¹

Directly, these medications bind to receptors on immune cells—including monocytes and macrophages—activating signaling pathways that inhibit the expression of inflammatory mediators. This multifaceted approach allows GLP-1 RAs to address the complex pathological triad of hyperglycemia, obesity, and chronic inflammation simultaneously.^1,2

Despite these clear clinical advantages, the Journal of the American College of Clinical Pharmacy emphasizes that significant barriers remain in the widespread implementation of these therapies. Pharmacists must navigate complex challenges related to high costs, insurance coverage gaps, and persistent supply chain disruptions that have led to intermittent shortages of semaglutide and tirzepatide.³

Furthermore, the authors also reported that 95% of pharmacists reported financial losses when dispensing these prescriptions due to low reimbursement rates, a trend that threatens the sustainability of providing these essential medications in community settings.³

The pharmacist’s role is therefore evolving into one of comprehensive clinical advocacy and education. Beyond managing inventory and costs, pharmacists are critical in mitigating the common gastrointestinal adverse effects—such as nausea and vomiting—that often lead to treatment discontinuation. They are also tasked with monitoring for rarer but serious risks, including gallbladder disease, potential psychiatric adverse events, and a black box warning for thyroid C-cell tumors. Additionally, pharmacists provide essential guidance on lifestyle modifications, such as ensuring adequate protein intake and resistance training to prevent the loss of lean muscle mass, or sarcopenia, which can accompany rapid weight loss.^3,4

By recognizing these agents as potent anti-inflammatory tools rather than just glucose-lowering medications, pharmacists can better optimize therapy, improve patient adherence, and contribute to the prevention of the long-term inflammatory damage that characterizes type 2 diabetes. This evolving landscape places the pharmacist at the center of a more nuanced, multimodal approach to chronic disease management that prioritizes long-term organ protection through the suppression of systemic inflammation.^1-3

READ MORE: Diabetes Resource Center

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REFERENCES

1. Zhao F, Wang H, Li S, Yun H, Su W. The effects of GLP-1 receptor agonists on metabolic inflammatory markers in patients with type 2 diabetes mellitus: a systematic review and meta-analysis. PeerJ. 2026;14:e20710. Published 2026 Feb 3. doi:10.7717/peerj.20710

2. Alrasheed T, Mostafa MEA, Madkhali MA, Khairy HA. Inflammatory biomarker response to GLP-1 receptor agonists versus other glucose-lowering medications in patients with type 2 diabetes: a systematic review and meta-analysis. Front Endocrinol (Lausanne). 2026;16:1734549. Published 2026 Jan 15. doi:10.3389/fendo.2025.1734549

3. Lingow S, Carris N, Clements J, Courtney L, Lennon A, Sherrill CH, Van Dril E. The pharmacist's role in the use of incretin-based therapies for weight management: an opinion of the endocrine and metabolism practice and research network of the American College of Clinical Pharmacy. ACCP. 2025; 8:1078–1093. doi/10.1002/jac5.70111

4. Cleveland Clinic. GLP-1 agonists. Updated July 3, 2023. Accessed February 10, 2026. https://my.clevelandclinic.org/health/treatments/13901-glp-1-agonists