We agree with Edelman (1) that the HypoCOMPaSS protocol (2) does not reflect current routine clinical practice. It was not our intention to replicate existing suboptimal clinical practice with regard to conventional multiple daily injection (MDI) therapy and self-monitoring of blood glucose (SMBG). Rather, the premise of our study focused on achievability within routine care. We do not agree that education, weekly telephone contact, and monthly visits (as part of a targeted 6-month intervention for those with impaired awareness of hypoglycemia [IAH]) should be dismissed as unachievable. We have shown the potential for a >10-fold reduction in severe hypoglycemia (SH)—including in those patients not receiving more costly technological interventions (2). Moreover, given increasing availability of bolus calculators on both handheld glucometers and cell phone apps, there is no reason why access should be limited to those using continuous subcutaneous insulin infusion (CSII) or real-time continuous glucose monitoring (RT-CGM).
Edelman highlights our intent to provide comparable education and support, but emphasizes that “device and glucose management education should differ for different devices” (1). This was indeed the case, as detailed in our initial protocol publication (3). Participants randomized to CSII or RT-CGM attended specific training sessions tailored to safe and effective use, while those randomized to MDI or SMBG attended comparable but distinct sessions also focused on optimized use. All participants were provided with clear and specific insulin titration protocols, previously reported in detail (3).
We question the assertion that there was “lack of glycemic benefit observed in the subjects who used pumps and CGM” (1), as our goal was active insulin titration to avoid biochemical hypoglycemia without worsening overall glycemic control. This was rapidly achieved in all groups within the first 4 weeks and maintained throughout the randomized controlled trial (2).
We accept that “consistency of use of the CGM device is a known key determinant for clinical benefit” (1) but do not agree that there was lack of clinical benefit in our study. RT-CGM was successful in improving IAH and preventing SH, and we observed that comparable benefits could be accrued from optimized SMBG. Of particular interest, although those using RT-CGM for >50% of the time appeared more successful in avoiding biochemical hypoglycemia and achieving best overall glycemic control, this did not translate to greater improvement in IAH and SH in this very high-risk group.
In the publication that Edelman cites as evidence for markedly higher adherence rates in clinical practice, 65% of respondents wore the Medtronic sensor for ≤1 week each month (4). Uninterrupted RT-CGM was advocated in our trial (3), but only 17% achieved >80% sensor usage (2), which provides evidence of likely real-world use with this iteration of the technology in unselected adults with IAH. This is in contrast to published efficacy studies, where those with SH have typically been excluded and only those prepared to wear sensors for the majority of the time were allowed to participate (5)—precluding extrapolation to real-world practice. Avoidance of positive selection of participants with confirmed RT-CGM tolerance also provides explanation for the relatively high rates of sensor site bleeding and local reactions in our study.
Funding. The HypoCOMPaSS study was funded by a peer-reviewed grant from Diabetes UK (07/0003556).
Duality of Interest. No potential conflicts of interest relevant to this article were reported.