This analysis of participant responses to a health status questionnaire conducted during a 16-week investigation comparing degludec with glargine found that degludec vs. glargine therapy produced a significant improvement in one dimension of health status, represented by mental component score. This was driven by significant gains in the social functioning and mental health domains.
In contrast, neither the other domains in the mental component score (vitality and role—emotional) nor any individual dimension of the physical component score were improved. Perhaps this is unsurprising as overall blood glucose control was similar, and therefore it might be expected that the overall biochemical functioning of most organ systems would not have differed between the insulins. In any case, it is likely that differences in glucose control would have to be large or very prolonged to affect these physical domains.
The relationship between diabetes and health status is complex, and it can be difficult to speculate which aspect of the insulin therapy may explain the observed result. The treat-to-target protocol employed resulted in comparable HbA1c levels, excluding glycaemic control as an explanation. A possibility is that the insulin delivery system used might affect a person’s assessment of their physical and mental status. As all participants from the USA randomized to glargine used vials/syringes, because of the unavailability of the pen injector specified in the protocol, this could potentially affect the results. However, no significant difference between treatments across the five countries included was detected, and therefore delivery system differences cannot explain the results found in this study.
The combination of fewer people experiencing at least one nocturnal hypoglycaemic event, together with the numerically lower overall (borderline significance) and statistically lower nocturnal hypoglycaemic event rates observed during the trial might explain the improved social functioning and mental health scores. Despite continued insulin therapy advances, people with diabetes still experience a substantial frequency of hypoglycaemia and it remains a limiting factor in diabetes management [15
]. A recent questionnaire-based study found that people self-tested more frequently and 25% of respondents reduced their insulin dose in the days following a non-severe hypoglycaemic event. Nocturnal hypoglycaemic events resulted in 23% of respondents arriving late or missing a day of work, while one third missed a meeting or deadline [16
]. A US internet-based questionnaire study found that people who self-reported low blood glucose symptoms had significantly lower mean utility scores (0.72 vs. 0.82 on the Euro-Qual Group EQ-5D measure, P
< 0.001), indicating a lower health-related quality of life, and were significantly more likely to report increased anxiety/depression (P
< 0.001) than people who did not experience low blood glucose symptoms in the preceding fortnight [17
It is possible that the ultra-long action profile and lower within-person glucose variability found with degludec [11
] may reassure users that their day-to-day glucose control is more stable, and this might improve health status. However, more work is needed to investigate the true relationship behind the observed significant health status improvement with degludec.
This study has its limitations. Participant numbers (n = 118), and thus statistical power, were low, so more subtle effect sizes could have been missed. However, those detected were of small-to-moderate effect size. It will be useful to see if these results can be reproduced in larger populations and in people with Type 2 diabetes mellitus. Additionally, this study was open-label, and there is a possibility that even after 16 weeks some halo effect surrounds the new insulin. Conversely, some of the participants used glargine pre-study and, for those changing to a relatively untried basal insulin preparation, anxiety could have induced increased mental burden, reducing the magnitude of the advantages identified here.
In the context of comparable overall glycaemic control to insulin glargine, insulin degludec treatment improved mental well-being as measured using the mental component score of the SF-36 questionnaire. Based on these findings, validation in a larger population during the Phase 3 investigations of insulin degludec would be advisable. Moreover, use of a larger population may allow an analysis in which it is possible to stratify SF-36 scores by presence or absence of hypoglycaemia.