Measuring Time in Range During CGM May Be Useful Outcome Metric for Clinical Trials
Investigators used data from the landmark Diabetes Control and Complications Trial, which demonstrated the association between hemoglobin A1C levels and the risk for diabetic vascular complications.
Derived from continuous glucose monitoring (CGM), the metric time in range (TIR), defined as 70 to 180 mg/dL (3.9 to 10 mmol/L), was found to be strongly related to microvascular complication risks in people with diabetes and could be a valuable outcome measure in clinical trials, according to study results published in Diabetes Care.
Although use of CGM has become more prevalent, the United States Food and Drug Administration has not begun accepting metrics pertaining to CGM as validated outcomes for new product efficacy claims, instead relying on hemoglobin A1c as the gold standard. In this study, researchers pooled data from 1440 participants from the Diabetes Control and Complications Trial data set. Glycemic data was measured at a central laboratory, with 7-point glucose concentration blood samples collected every 3 months.
CGM was not available at the time of the original study, but participants self-collected data 7 times a day (before meals, 90 minutes after meals, and at bedtime). The researchers used this data to assess the association between TIR with retinopathy progression and urinary microalbuminuria using proportional hazard models.
Mean TIR of the participants with diabetes was 41 ± 16% (52 ± 10% in the intensive treatment group vs 31 ± 12% in the conventional treatment group [P <.001]). The hazard rate for the development of retinopathy progression grew by 64% (95% CI, 51-78) and the rate for microalbuminuria increased by 40% (95% CI, 25-56) for each decrease of 10 percentage points in TIR (P <.001). Findings were similar for mean glucose and hyperglycemia measurements computed from the 7-point testing.
Researchers concluded that “TIR is strongly associated with the risk of microvascular complications and should be an acceptable end point for clinical trials.”
One author declared affiliation with multiple pharmaceutical companies. See reference for a full list of disclosures.
Beck RW, Bergenstal RM, Riddlesworth TD, et al. Validation of time in range as an outcome measure for diabetes clinical trials [published online October 23, 2018]. Diabetes Care. doi:10.2337/dc18-1444