Time in Range and Adverse Outcomes in Type 2 Diabetes: A Quantitative Synthesis

Objective: We aimed to quantify the prognostic value of glucose monitoring-derived time in range (TIR), including continuous glucose monitoring (CGM), flash glucose monitoring (FGM), and fingertip capillary glucose monitoring (FCGM), for predicting adverse clinical outcomes in patients with type 2 diabetes mellitus (T2DM). Research Design and Methods: PubMed, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL, via OVID) were systematically searched from 2017 to November 2025 for studies evaluating the risk of all clinically relevant outcomes associated with different TIRs in T2DM. Extracted data were standardized to evaluate the effect of a 10% increment in TIR. Pooled estimates were calculated using inverse-variance random-effects models incorporating dose-response analysis. The certainty of evidence was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) framework. Results: Twenty-four observational studies involving 20 distinct associations and 35,916 participants were included. Dose-response meta-analyses were conducted for nine associations. The results showed that each 10% increment in TIR was significantly associated with a reduced risk of multiple adverse complications, including all-cause mortality (odd ratio [OR] = 0.88, 95% confidence interval [CI]: 0.82-0.93), vision-threatening diabetic retinopathy (OR = 0.93, 95% CI: 0.87-0.98), diabetic retinopathy (OR = 0.92, 95% CI: 0.89-0.95), lower extremity atherosclerotic disease (OR = 0.86, 95% CI: 0.82-0.91), diabetic peripheral neuropathy (OR = 0.77, 95% CI: 0.71-0.84), and cardiovascular autonomic neuropathy (OR = 0.81, 95% CI: 0.68-0.97). In contrast, the associations for albuminuria (KDIGO [Kidney Disease: Improving Global Outcomes] A2 and A3) and amputation did not reach statistical significance in the primary meta-analysis. Conclusions: In conclusion, each 10% increment in TIR is consistently associated with a reduced risk of mortality and various micro- and macrovascular complications in T2DM. These findings suggest TIR as a robust prognostic indicator and actionable therapeutic target in diabetes management.