Real-World evidence in clinical trials
A Real-World look of time in range (TIR) and glucose management indicator (GMI)
Background and Aims / Part 1
It has become common place for us to compare various patient registries in terms of A1C, rates of DKA, and severe hypoglycemia. We were curious to better understand glucometrics from CGM in the University of Washington Diabetes Care Center.
Methods / Part 2
From March 2017 to November 2019 we reviewed 247 patients with type 1 diabetes using CGM.
Results / Part 3
Average age was 52 years, average duration of diabetes was 28 years, half were women, and mean A1C was 7.2%. Sixty percent used Dexcom, 29% used Medtronic, and 11% used the Abbott Libre. Mean glucose was 163 mg/dL with a percent coefficient of variation (CV) of 34.8%. TIR for the population was 60.4% with Time Below Range (TBR) of 3.5%. GMI was 7.2%. Using mean glucose to predict GMI, 34% and 7% of measured A1C values were at least 0.5% and 1% discordant respectively.
Conclusions / Part 4
It is concluded that current consensus guidelines for TIR are reasonable. Percent CV below or equal to 33% is possible in T1D despite arguments this target should be below 36%. Finally, the GMI equation closely approximates our population’s CGM data.
Time in range and diabetes complications
Conclusions / Part 4
Although HbA1c remains a valuable metric for assessing glycemic control, its limitations are well recognized. Time in range (TIR) of 70-180 mg/dL (3.9-10 mmol/L) has been popularized as an important measure of glycemic control for clinical trials and diabetes management. Surveys have shown that TIR is recognized as an important outcome by patients. Using data from the Diabetes Control and Complications Trial, it has been shown that TIR calculated from quarterly 7-point blood glucose measurements is strongly associated with the development or progression of retinopathy and microalbuminuria. For each 10 percentage points lower TIR, the rate of development of retinopathy progression was increased by 64% and the rate of development of the microalbuminuria outcome was increased by 40%. A study from China also has demonstrated a strong association between TIR and retinopathy in type 2 diabetes. The strength of the association of TIR with microvascular complications appears to be of similar magnitude to that of HbA1c with complications. Based on these findings, a compelling case can be made that TIR is strongly associated with the risk of microvascular complications and should be an acceptable endpoint for clinical trials as well as a valuable metric in the clinical care of people with diabetes.