The impact of metformin and aspirin on T-cell mediated inflammation: A systematic review of in vitro and in vivo findings

Chronic inflammation and hyperglycaemia are well-established aspects in the pathogenesis of type 2 diabetes mellitus (T2D), including the progression of its associated complications such as cardiovascular diseases (CVDs). In fact, emerging evidence shows that dysfunctional immune responses due to dysregulated T-cell function aggravates CVD-related complications in T2D. However, there is a lack of specific therapeutic interventions that protect patients with diabetes who are at risk of heart failure. Metformin and aspirin are among the leading therapies being used to protect or at the very least slow the progression of CVD-related complications. The current review made use of major electronic databases to identify and systematically synthesise emerging experimental data on the impact of these pharmacological drugs on T-cell responses. The quality and risk of bias of include evidence were independently assessed by two reviewers. Overwhelming evidence showed that both metformin and aspirin can ameliorate T-cell mediated inflammation by inducing regulatory T-cells (Tregs) polarisation, inhibiting T-cell trafficking and activation as well as signal transducer and activator of transcription (STAT)3 signalling. As a plausible mechanism to mediate T-cell function, metformin showed enhanced potential to regulate mechanistic targets of rapamycin (mTOR), STAT5 and adenosine-monophosphate-activated protein kinase (AMPK) signalling pathways. Whilst aspirin modulated nuclear factor kappa-light-chain-enhancer of activated B-cells (NF-kB) and co-stimulatory signalling pathways and induced T-cell anergy. Overall, synthesised data prompt further investigation into the combinational effect of metformin and aspirin for the management of T2D-related cardiovascular complications.