We thank Hamidi and Pettus (1) as well as Stoet and Holt (2) for the discussion on time in tight range 70–140 mg/dL (TITR). They focused on hypoglycemia risk if TITR targets get implemented. We acknowledge that safety is paramount for people living with type 1 diabetes (T1D). Historically, striving for lower HbA1c has indeed been associated with an increased hypoglycemia risk. However, the point we want to make is that with the MiniMed 780G system (MM780G), TITR and hypoglycemia targets are mostly unlinked. Our second point is that we believe it is the right time to implement TITR targets, but it is most relevant for people living with type 1 diabetes aiming for normoglycemia using automatic insulin delivery systems.
In terms of TITR and hypoglycemia targets being unlinked, we refer to our publication (3), where we examined the interdependency of continuous glucose monitoring (CGM) targets in >55,000 real-world MM780G users. Here, we demonstrated that targets are grouped into two domains: the euglycemic domain, including targets for glucose management indicator (GMI), time in range (TIR) 70–180 mg/dL, TITR, time above 180 mg/dL, and time above 250 mg/dL, and the hypoglycemic domain, including targets for time below 70 mg/dL and time below 54 mg/dL. At least one metric per domain is needed for managing CGM targets. The data show that time in hypoglycemia is largely independent of meeting even the stringent GMI target of <6.5%, implying that meeting hypoglycemia targets can be achieved while meeting targets in the euglycemia domain. This conclusion is supported by our previous real-world studies that showed high TITR while maintaining low levels of hypoglycemia (and of hyperglycemia, another safety concern raised by Stoet and Holt) (4). The unlinking can be partly explained by the MM780G safety modules that use predictions to determine if a meal or correction bolus might lead to hypoglycemia and reduces the bolus if necessary. Further research is needed to determine if the unlinking also applies to other automatic insulin delivery systems.
In terms of TITR being appropriate for individuals with T1D who are aiming for normal glycemia, a post hoc analysis (n > 55,000) demonstrated a strong Spearman correlation between TITR and GMI <7.0% (−0.93, n = 36,110) and a slightly weaker correlation for GMI ≥7% (−0.84, n = 20,542). In contrast, TIR shows its strongest correlation with higher GMIs (−0.89 for GMI ≥7%) and a weaker correlation with lower GMIs (−0.79 for GMI <7%). This implies that TITR may be a better metric for people with T1D with a glucose control that is closer to normoglycemia, which is achievable with advanced technology. Second, a high TIR does not necessarily reflect a high TITR. Using data of >140,000 MM780G users, we identified TIR and TITR targets corresponding to GMI <7% and GMI <6.5% (by receiver operating characteristic curves). For targets corresponding to GMI <7% (TIR >70%, TITR >46%), 15.0% of users meeting TIR target did not meet TITR target, while only 5.9% meeting TITR target did not meet TIR target. For targets corresponding to GMI <6.5% (TIR >80%, TITR >58%), the former percentage was 38.7% while the latter remained low at 6.4%. Additionally, TITR is a better predictor of euglycemia (3).
In summary, achieving near-euglycemia control without compromising safety is feasible with MM780G, as hypoglycemia is mostly unlinked from TITR targets. Second, it is important that individuals with T1D aiming for normal glycemia adopt TITR targets (e.g., by using advanced diabetes technology). Glucose targets must be individualized, and TIR remains appropriate for those aiming at GMI ≥7%.
Article Information
Duality of Interest. J.C., T.v.d.H., and O.C. are employees of Medtronic. No other potential conflicts of interest relevant to this article were reported.
Handling Editors. The journal editors responsible for overseeing the review of the manuscript were Steven E. Kahn and Thomas P.A. Danne.
