We appreciate that Pogach and Aron (1) disagree with our commentary (2). It is logical to assume, as these authors appear to have done, that lower HbA1c is associated with greater likelihood of hypoglycemia. We reiterate that a great deal of evidence, some discussed in our commentary (2), supports the notion that HbA1c levels in the “good” range are associated with better outcome rather than with more hypoglycemia. Indeed, agents reducing cardiovascular end points, not causing hypoglycemia, and allowing good control (at any age) are available.
Are older adults specifically ill-suited to “good” control? An Action to Control Cardiovascular Risk in Diabetes (ACCORD) analysis showed that individuals age 65 and older had no increase in cardiovascular or total mortality with intensive versus standard glycemic control (hazard ratios 0.97 and 1.06, respectively), while individuals below age 65 had 1.71-fold and 1.42-fold increases in cardiovascular and total mortality, respectively (3). The intensive intervention decreased nonfatal myocardial infarction (a macrovascular end point) and reduced microvascular end points (2); we assume that Pogach et al. will not make use of this insight to revise their proposal (4) to “An Out-of-Range Glycemic Population Health Safety Measure for Younger-Than-65-Year-Old Adults With Diabetes.” An important additional point: Pogach and Aron (1) appear to assume that the relationship between anemia and lower HbA1c directly reflects the lower erythrocyte count. Rather, HbA1c decreases with shorter erythrocyte life span, well recognized in the setting of hemolysis, but not as widely appreciated to exist to a lesser degree with other conditions associated with change in erythrocyte turnover (5,6).
Louis Lasagna was a founder of clinical pharmacology in its current form, and we appreciate Pogach and Aron referencing Lasagna’s revision of the Hippocratic oath. We respectfully reciprocate with a less well-known article by Lasagna, entitled “Consensus Among Experts: The Unholy Grail” (7). The article concludes by quoting Oliver Cromwell’s request: “Think it possible you may be mistaken.”
Duality of Interest. Z.T.B. has been a consultant/advisor for AstraZeneca, Johnson & Johnson, Merck, Intarcia, and Novartis; a speaker for Merck, AstraZeneca, and Johnson & Johnson; and is a stockholder in Allergan, Pfizer, Zimmer Biomet, and Novartis. D.E. has been a consultant for Eli Lilly, Novo Nordisk, Sanofi, Janssen, Adocia, Medtronic, Takeda, Halozyme, Freedom Meditech, Epitracker, Nexus BioPharma, Intarcia, and GlySens; has been involved with research for Eli Lilly, Novo Nordisk, Sanofi, MannKind, Janssen, AstraZeneca, Freedom Meditech, and Adocia; and is a shareholder in Halozyme, GlySens, Epitracker, Nexus BioPharma, and Freedom Meditech. Y.H. has received research grants and consultant and speaker honoraria from Amarin, Amgen, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Boehringer Ingelheim–Eli Lilly, Esperion, Grifols, GlaxoSmithKline-Hanmi, Intarcia, Janssen, Lexicon, Eli Lilly, Merck, Novo Nordisk, Pfizer, Regeneron, and Sanofi. No other potential conflicts of interest relevant to this article were reported.