We appreciate the comments from Chen et al. (1) on our recent study investigating the relationship between diabetes overtreatment and hypoglycemia in older adults with type 2 diabetes (T2D) on insulin therapy (2). We welcome this opportunity to clarify key points and further engage in this discussion.
First, regarding the association between insulin regimens and time below range (TBR), we recognize the importance of such analyses. These were, however, already addressed in the primary HYPOAGE publication (3). In univariate analyses, we observed that basal-bolus regimens and continuous subcutaneous insulin infusion were associated with an increased risk of hypoglycemia (odds ratio 2.16 [95% CI 1.07–4.36]) compared with basal insulin monotherapy. Additionally, the use of dipeptidyl peptidase 4 inhibitors was linked to a lower risk of hypoglycemia (odds ratio 0.37 [95% CI 0.15–0.93]). However, after multivariable adjustment, these associations were not statistically significant, highlighting the influence of confounding factors. Furthermore, our prior investigations found no significant association between malnutrition and confirmed hypoglycemia (≤70 mg/dL) (3). Beyond glucose-lowering agents, we did not investigate the potential association of other drugs (e.g., antihypertensive treatments) with hypoglycemia.
Regarding the hypoglycemia thresholds recommended by recent guidelines for older adults (TBR ≥1% [≥15 min/day below 70 mg/dL]), which were used in our study, we agree with the authors that these targets might seem too challenging to achieve (4). However, while the feasibility of recommendations is indeed crucial for their implementation, it is not their primary focus. The patient-centered therapeutic optimization strategy for older adults aims to maximize benefits, which do not necessarily or exclusively correspond to strict glycemic control, while minimizing treatment-related risk of harm (4). Furthermore, these recommendations provide targets, an objective to strive for, while also helping to prevent therapeutic inertia.
We are witnessing the early stages of recommendations regarding TBR targets, and ongoing discussions will likely lead to further refinements and improvements. For instance, some colleagues advocate for a buffer zone approach (70–90 mg/dL) and aiming for a TBR of 0% (5). While we respect the authors’ perspective, a sensitivity analysis on TBR levels would be neither appropriate nor reliable to assess whether glycemic control strategies are both effective and achievable in this population given our sample size and study design.
Finally, we appreciate the discussion on barriers to the use of technology in older adults. Indeed, several age-related factors, including, for example, dexterity issues and technological literacy, may challenge its use in this population. Nevertheless, as our study highlights the potential benefits of technology in identifying and mitigating hypoglycemia in this population, addressing these barriers should be prioritized in future research. Recent guidelines on the use of technology in older adults reflect its increasing clinical relevance, and further efforts should focus on improving its accessibility and integration into routine care (4).
In conclusion, further research is needed to refine the definition of overtreatment and help in guiding clinicians in selecting the safest and most beneficial therapeutic strategies for older patients with T2D.
Article Information
Funding. This investigator-sponsored study was funded by Sanofi, which had no role in the design, methods, recruitment, data collection, or the analysis and preparation of the article.
Duality of Interest. B.C. reports grants from Amgen, LVL-Air Liquide, Sanofi, and Ypsomed and personal fees from Abbott, Amgen, AstraZeneca, Bristol Myers Squibb, Eli Lilly and Company, LVL-Air Liquide Novartis, Novo Nordisk, Sanofi, and Ultragenyx. S.H. reports receiving grants from Asten, AstraZeneca, Homeperf, LVL-Air Liquide, Nestle Home Care, Pierre Fabre, and VitalAire; consulting fees from AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Novo Nordisk, Sanofi, Servier, and Valbiotis; speaking fees from Abbott, AstraZeneca, Boehringer Ingelheim, Bayer, Dino Santé, Eli Lilly, Novartis, Novo Nordisk, Pierre Fabre, Sanofi, Servier, and Valbiotis; and meeting invitations from AstraZeneca, Abbott, Dino Santé, Eli Lilly, and Novo Nordisk. 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 Vanita R. Aroda.
