Agent-specific, histopathology-stratified hematologic malignancy risk among dpp-4 inhibitors, glp-1 receptor agonists, and SGLT2 inhibitors: a network meta-analysis of 270,471 participants
Abstract
Dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, and sodium–glucose cotransporter 2 (SGLT2) inhibitors are widely prescribed for their cardiometabolic benefits, yet their hematologic oncologic safety remains uncertain. Because hematologic malignancies are highly lethal and biologically heterogeneous, delineating drug-specific risks across histopathologic subtypes is clinically crucial. This histopathology-stratified network meta-analysis (NMA) evaluated and compared the hematologic malignancy risks associated with individual agents from these drug classes. Following Cochrane guidance for adverse-event synthesis, we conducted this frequentist-based NMA of randomized controlled trials (RCTs). The primary endpoint was incident hematologic malignancy, categorized a priori into leukemia (acute and chronic forms), lymphoma (Hodgkin and non-Hodgkin), and myeloma/plasma cell neoplasms. Bayesian models were used as sensitivity analyses. Seventy-five RCTs including 270,471 participants were eligible. Dulaglutide was associated with a significantly increased risk of overall hematologic malignancy (RR = 2.17, 95% CIs = 1.14–4.17). In contrast, tirzepatide (RR = 0.22, 95% CIs = 0.06–0.78) and linagliptin (RR = 0.51, 95% CIs = 0.27–0.95) were linked to a reduced overall risk. In histopathology-specific analyses, tirzepatide showed a significant protective association against non-Hodgkin’s lymphoma, whereas no agent demonstrated clear signals…
How strong is the evidence?
Evidence Hub reads this as a meta-analysis, done in people. Its evidence level is 1 of 5 (Highest · pooled evidence). Pooled evidence from several studies sits at the top of the evidence pyramid. Reported size: 270,471 participants or records.
Read the paper
Related studies
- Strategy for Mitigating DKA Risk in Patients with Type 1 Diabetes on Adjunctive Treatment with SGLT Inhibitors: A STICH Protocol
- Glucoraphanin: a broccoli sprout extract that ameliorates obesity-induced inflammation and insulin resistance
- SGLT2 Inhibitors in Heart Failure: Targeted Metabolomics and Energetic Metabolism
- Mechanisms of blood pressure reduction with sodium-glucose co-transporter 2 (SGLT2) inhibitors
- Sodium-glucose cotransporter inhibitors: beyond glycaemic control
- Decoding the effects of SGLT2 inhibitors on cardiac arrhythmias in heart failure
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.