A1C targets should be personalized to maximize benefits while limiting risks
Open accessAbstract
A set of guidance statements recently published by the American College of Physicians (ACP) advocates relaxation of goals for control of glycated hemoglobin (A1C) by people with type 2 diabetes (T2D) (1). This publication advises that “clinicians should reevaluate HbA1c levels and revise treatment strategies on the basis of changes in the balance of benefits and harms.” Specifically, it proposes reducing pharmacotherapy for any person when A1C is <6.5%, seeking a level between 7 and 8% for “most patients,” and aiming only to minimize symptoms without any specific A1C goal for those over age 80 years or with chronic medical conditions likely to limit life expectancy. These recommendations are at odds with those of other professional organizations, including the American Diabetes Association (ADA) (2–5). We believe the ACP recommendations fail to consider several important bodies of scientific evidence, and if they are widely adopted in clinical practice, the recent progress in management of diabetes may be threatened. Each of the ACP’s recommendations requires specific comments. These will be followed by a more general discussion of our concerns. The ACP’s main justification for decreasing therapy whenever A1C is <6.5% is the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial’s finding of ∼20% increased mortality—mostly from cardiovascular (CV) events—when the median A1C attained by intensive treatment was 6.4% (6). However, this generalized advice does not acknowledge experience in other trials. In contrast to ACCORD, the Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation (ADVANCE) trial (7) and the Veterans Affairs Diabetes Trial (VADT) (8), which similarly enrolled high-risk patients and sought A1C levels <7%, did not show increased short-term CV risk or mortality. Importantly, the newly diagnosed, low-risk participants in the UK Prospective Diabetes Study (UKPDS) also showed no tendency toward increased early mortality …
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The greatest absolute risk reduction in glucose control comes from improving very elevated glycemic levels, while a more modest reduction results from near normalization of plasma glucose levels.
“The greatest absolute risk reduction comes from improving very elevated glycemic levels, and a more modest reduction results from near normalization of plasma glucose levels (2,14).”
From Management of Hyperglycemia in Type 2 Diabetes, 2022. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) (2022) · cites this paper as [14]
In “A1C Targets Should Be Personalized to Maximize Benefits While Limiting Risks” (page not available in our copy), the paper says lower A1C is associated with lower long-term complication risks and describes benefits from seeking near-normal glucose levels. It does not compare absolute risk reductions from improving very elevated levels with those from near-normalization, so the claimed ranking of benefits is unsupported. (LLM, conf=0.83)
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Davies, M. J., D’Alessio, D. A., Fradkin, J., Kernan, W. N., Mathieu, C., Mingrone, G., Rossing, P., Tsapas, A., Wexler, D. J., & Buse, J. B. (2018) · Diabetes Care · doi:10.2337/dci18-0033 · Cited by 3,518 · see citing works
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- Authors
- Riddle, M. C., Gerstein, H. C., Holman, R. R., Inzucchi, S. E., Zinman, B., Zoungas, S., & Cefalu, W. T.
- Affiliations
- Oregon Health & Science University (US)
- Population Health Research Institute (CA)
- University of Oxford (GB)
- Yale University (US)
- Mount Sinai Hospital (CA)
- Monash University (AU)
- American Diabetes Association (US)
- Corresponding author
- Riddle, Matthew C.
- ORCID
- Venue
- Diabetes Care
- Publisher
- American Diabetes Association
- Published
- 2018-05-11
- Volume
- 41
- Issue
- 6
- Pages
- 1121-1124
- ISSN
- 0149-5992 (ISSN-L)
- 1935-5548
- OpenAlex
- W2803869903
- Cited by
- 54
- References
- 49
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 2 · 2023: 3 · 2022: 7 · 2021: 8 · 2020: 16 · 2019: 8 · 2018: 5
- FWCI
- 7.41
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Diabetes Care (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Keywords
- HbA1c, HbA1c targets, type 2 diabetes, ACCORD trial, cardiovascular risk, mortality, ADVANCE trial, UKPDS, older adults
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