The Saudi Journal of Medical Insights

Background: Chronic low-grade inflammation contributes to diabetic kidney disease and atherosclerotic events in type 2 diabetes (T2D), but evidence for immunomodulatory therapy is fragmented across agents and outcomes.
Objective: To compare the effects of immunomodulatory therapies on chronic kidney disease (CKD) progression and cardiovascular outcomes in adults with T2D.
Methods: Following PRISMA 2020, we included randomized trials and observational studies published from 2009 to 2026 that evaluated pentoxifylline, colchicine, interleukin-1 or interleukin-6 inhibitors, methotrexate, or Janus kinase inhibitors in adults with T2D. Risk of bias was assessed with RoB 2 and ROBINS-I, certainty with GRADE, and results were synthesized narratively because pooling was inappropriate.
Results: Eleven studies were included (eight randomized trials, two randomized-trial subgroup analyses, one cohort). In advanced diabetic CKD, pentoxifylline slowed estimated glomerular filtration rate decline (−2.1 vs −6.5 mL/min/1.73 m² over 24 months in one trial) and reduced albuminuria, whereas one short trial in early disease was null. Colchicine reduced cardiovascular events after myocardial infarction (HR 0.65, 95% CI 0.44–0.96). Canakinumab showed a similar but imprecise effect in diabetes (HR 0.85, 0.70–1.03); methotrexate was neutral (HR 1.01, 0.82–1.25). Baricitinib lowered albuminuria by 41%.
Conclusions: Effects are agent-specific. Pentoxifylline slowed CKD progression and reduced albuminuria, and colchicine reduced cardiovascular events in T2D; canakinumab showed a directionally consistent but imprecise benefit, methotrexate was neutral, and baricitinib lowered albuminuria. Certainty is low to moderate, and adequately powered T2D-specific trials with hard outcomes are needed.