Safety and Efficacy of Canakinumab for the Prevention and Control of Type 2 Diabetes Mellitus and Its Complications: A Systematic Review.

Abstract

Today, diabetes mellitus (DM) is one of the leading causes of morbidity and mortality globally.In this grim context, while our current armamentarium of anti-diabetic agents is vast and increasingly available, glycemic control in a significant proportion of these patients continues to remain sub-optimal.This necessitates the exploration of other potential cellular pathways and targets to effectively manage this notorious disease and its numerous complications. Inflammatory responses are thought to be implicated in the decline of pancreatic beta-cell function, with interleukin-1 beta (IL-1β) playing an important role in these pathways. Canakinumab, a human monoclonal anti-IL-1β antibody, operates by reducing inflammation, potentially safeguarding or enhancing pancreatic beta-cell function. This systematic review aims to study the safety and efficacy of canakinumab in the prevention and control of type 2 diabetes mellitus (T2DM) and its complications. This study was conducted in accordance with the PRISMA 2020 Guidelines. PubMed including MEDLINE, Google Scholar and Cochrane Library were used as information sources and randomized clinical trials and retrospective observational studies evaluating patients with T2DM or impaired glucose tolerance with/without complications receiving canakinumab, compared with placebo or standard therapy and reporting about glycemic indicators including hemoglobin A1C (HbA1C) or blood sugar levels (BSL) or insulin levels and/or inflammatory indicators including high-sensitivity C-reactive protein (hsCRP) or interleukin-6 (IL-6) were included. Non-randomized clinical trials, animal studies, review articles, case reports, case series, studies not in the English language and those evaluating type 1 DM were excluded. In total, 271 studies were identified to be included in this study. Subsequently, 27 were found to be duplicate records and were eliminated. Manual screening of title/abstract of 244 records was done which found 207 to be ineligible and 37 studies were shortlisted. These were retrieved and full-text screening was undertaken which resulted in the exclusion of 28 reports due to the following reasons: ineligible study design (17), studies evaluating type 1 DM (three), studies evaluating anakinra (one), trial being canceled (three) and duplicate studies (four). Subsequently, a total of nine studies were included in the final review. All studies were included post quality appraisal. We found that canakinumab had a modest but mostly non-significant effect on glycemic parameters including HbA1C, while having a consistently significant reduction in systemic inflammatory parameters like hsCRP and IL-6. Additionally, it was found to have a significant reduction in incident major adverse cardiovascular events (MACE). Canakinumab was also found to be safe and well-tolerated in all patient populations. Although canakinumab did not reduce incident T2DM, an exploration of alternative pathways and targets implicated in the pathogenesis of this disease process is warranted for the prevention and control of T2DM.