The Burden of Uncontrolled Glycemia—A Systematic Literature Review

Abstract

The objective of this systematic literature review (SLR) was to understand the consequences of uncontrolled glycemia in patients with type 2 diabetes mellitus (T2DM) in terms of mortality, macro- or microvascular complications, as well as economic burden in terms of healthcare resource utilization (HCRU) and cost. A predefined search strategy was used in Medline, EMBASE, Cochrane CENTRAL, EconLit and NHS-EED, limited to the last five years, according to PRISMA guidelines. In terms of mortality and clinical data, twenty-two studies met our inclusion criteria. Five studies reported significantly increased risk of mortality for A1C greater than 7.5% (Hazard ratio (HR) ranged from 1.41-13.16). Three studies reported an increased risk of mortality for every 1% increase in A1C above 7% (HR from 1.10-1.40). In one landmark trial (ACCORD), however, comparing intensive (A1C target <6.0%) to standard glycemic control (A1C target 7.0-7.9%), a higher risk of all-cause mortality in the intensive group was reported. Six studies showed that A1C higher than 7% was associated with an increased risk of macrovascular complications (HR / odds ratio (OR) from 1.13-2.26) and three studies reported that every 1% increase in A1C above 7% resulted in an increased risk of different macrovascular complications (HR / OR from 1.05-1.38). Three studies reported higher risk (HR / OR from 1.13-1.40) of microvascular events at A1C higher than 7%. For the economic data, 1 U.S. study reported increased healthcare cost (OR 1.73 (95% CI 1.00-3.01) for T2DM patients with A1C greater than 10%. In another U.S. study, 1% increase in A1C between 7-10.5% was associated with additional diabetes-related pharmacy/medical cost burden of $1586 ($133-$3537) per patient per year. Three non-U.S. studies also reported similar results on the association of A1C and economic burden. Our SLR showed an association between high A1C and increased risk of clinical outcomes, including mortality. Furthermore, poor glycemic control was also associated with increased HCRU and costs. Disclosure G. Fernandes: Employee; Self; Merck & Co., Inc.. Employee; Spouse/Partner; Janssen Research & Development. Stock/Shareholder; Self; Merck & Co., Inc.. Stock/Shareholder; Spouse/Partner; Janssen Research & Development. J. Iff: None. O. Ovcinnikova: None. M. Nassim: None. L. Sun: None. M.S. Richards: None. S. Rajpathak: Employee; Self; Merck & Co., Inc..