Assessing the Incidence of New-onset Diabetes Mellitus with Statin Use: A Systematic Review of the Systematic Reviews and Meta-analyses

Abstract

Statin use has been linked with new-onset diabetes mellitus (NODM). In the present systematic review, we aimed to determine the incidence of NODM with statin use by assessing and summarizing the data generated by different systematic reviews and metaanalyses published on this topic. We conducted a systematic review of systematic reviews and meta-analyses using a pre-defined study protocol. Two authors independently performed a literature search using PubMed, Embase and the Cochrane Central Register of Controlled Trials (CENTRAL) for studies reporting data on statin use and NODM incidence and screened and extracted data for the outcomes of interest. The Assessing the Methodological Auality of Systematic Reviews 2 (AMSTAR 2) checklist was used to evaluate the quality of the included systematic reviews and meta-analyses. The initial search yielded 621 potential records, and 16 relevant systematic reviews and meta-analyses were included in the present systematic review. The included studies showed an increase in the risk of NODM with statin use. In particular, rosuvastatin and atorvastatin were associated with NODM in many systematic reviews or meta-analyses; however, pravastatin and pitavastatin were found to be associated with lower or no risk. We observed a positive trend of development of NODM with statin use became more evident with advancing years as more number of studies were added. Intensive doses of statins and use in older subjects were found to be important risk factors for NODM. Finally, the quality assessment revealed that the included systematic reviews and metaanalyses were of critically low or low quality. We concluded that statin use carries a risk of causing NODM. Statins should not be discouraged in anticipation of NODM. However, glycaemic monitoring should be encouraged with the on-going statin therapy. Furthermore, clinical studies addressing the use of statins and the incidence of NODM as their primary objective should be planned.

Traditional Therapeutics and Potential Epidrugs for CVD: Why Not Both?

“…There is also evidence of the onset of T2DM with statin therapy; however, the findings of these studies are still controversial [75,115,116]. Specifically, characteristics such as the type of statin-for example, rosuvastatin or atorvastatin, -age, and other risk factors have been exhibited to contribute to this onset [117]. A mechanism that can contribute to both the onset of T2DM and the common myopathic side effects of statins is the inhibition of byproducts from the mevalonate pathway that play roles in mitochondrial health, calcium channel activity, and insulin signaling [118][119][120].…”

Sex-differences in reporting of statin-associated diabetes mellitus to the US Food and Drug Administration

“…9 The mechanisms of statininduced DM are unclear but may include decreased insulin production by pancreatic β-cells, decreased production of ubiquinone, decreased GLUT4 adipocytes, or inhibition of glucosemediated insulin release in cells. 10 Awareness of DM as a potential consequence of statin use is growing and is now included in patient-facing educational resources from agencies like the Centers for Disease Control. 11 Despite growing acceptance of DM as an adverse side effect of statins, there is relatively little data directly comparing risk between men and women.…”

“…9 The mechanisms of statin-induced DM are unclear but may include decreased insulin production by pancreatic β-cells, decreased production of ubiquinone, decreased GLUT4 adipocytes, or inhibition of glucose-mediated insulin release in cells. 10…”