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  • Review Article
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The trials and tribulations of determining HbA1c targets for diabetes mellitus

Nature Reviews Endocrinology volume 16, pages 717–730 (2020)Cite this article

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Abstract

Glycated haemoglobin (HbA1c) is considered the gold standard for predicting glycaemia-associated risks for the microvascular and macrovascular complications of diabetes mellitus over 5–10 years. The value of HbA1c in the care of patients with type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) is unassailable, yet HbA1c targets remain contentious. Guidelines from diabetes care organizations recommend conflicting HbA1c targets — generally between 6.5% and 8%. However, all such organizations advocate for individualization of HbA1c targets, leaving both health-care providers and their patients confused about what HbA1c target is appropriate in an individual patient. In this Review, we outline the landmark T1DM and T2DM trials that informed the current guidelines, we discuss the evidence that drives individualized HbA1c targets, we examine the limitations of HbA1c, and we consider alternatives for monitoring glycaemic control. Ultimately, in synthesizing this literature, we argue for an HbA1c target of <7% for most individuals, but emphasize the importance of helping patients determine their own personal goals and determinants of quality of life that are independent of a particular glycaemic target. We also recognize that as newer technologies and anti-hyperglycaemic therapies emerge, glycaemic targets will continue to evolve.

Key points

  • Glycated haemoglobin (HbA1c) targets are controversial due to conflicting results from large-scale clinical trials in patients with type 1 and type 2 diabetes mellitus.

  • Observational studies in patients with type 1 diabetes have shown that achieving an average HbA1c of ≤7.5% over 25 years is associated with a low risk of disabling microvascular complications.

  • Data from large-scale outcome trials in patients with type 1 and type 2 diabetes mellitus have demonstrated that achieving an HbA1c of ~7% is associated with microvascular benefit as compared with higher levels of HbA1c, but less clear evidence exists for macrovascular outcomes.

  • Although it is the gold standard for monitoring glycaemic control, HbA1c has limitations that are not widely appreciated.

  • The advent of novel technology (especially continuous glucose monitors) and therapeutic agents (GLP1 receptor agonists and SGLT2 inhibitors) have created additional reasons for a more flexible approach to selecting HbA1c treatment targets. No tool, technology or pharmacotherapy will replace the importance of shared decision-making based on mutual respect and understanding between patients and health-care providers to individualize HbA1c targets.

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Fig. 1: CGM-measured mean glucose concentration versus HbA1c.

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Acknowledgements

K.R.K. acknowledges the support of the University of North Carolina Department of Medicine Physician Scientist Training Program. J.B.B. acknowledges the support of grants from the National Institutes of Health (UL1TR002489, P30DK124723). The reviewers were extremely helpful in suggesting numerous important revisions.

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  1. Division of Endocrinology and Metabolism, University of North Carolina School of Medicine, Chapel Hill, NC, USA

    Klara R. Klein & John B. Buse

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  1. Klara R. Klein
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K.R.K. wrote the article. Both authors contributed equally to researching data for the article, made substantial contributions to discussion of content, and reviewed/edited the manuscript before submission.

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Correspondence to Klara R. Klein.

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Competing interests

J.B.B.’s contracted consulting fees and travel support for contracted activities are paid to the University of North Carolina by Adocia, AstraZeneca, Dance Biopharm, Dexcom, Eli Lilly, Fortress Biotech, Fractyl, GI Dynamics, Intarcia Therapeutics, Lexicon, MannKind, Metavention, NovaTarg, Novo Nordisk, Orexigen, PhaseBio, Sanofi, Senseonics, vTv Therapeutics, and Zafgen; he reports grant support from AstraZeneca, Eli Lilly, Intarcia Therapeutics, Johnson & Johnson, Lexicon, Medtronic, NovaTarg, Novo Nordisk, Sanofi, Theracos, Tolerion, and vTv Therapeutics; he is a consultant to Cirius Therapeutics Inc., CSL Behring, Mellitus Health, Neurimmune AG, Pendulum Therapeutics, and Stability Health; he holds stock/options in Mellitus Health, Pendulum Therapeutics, PhaseBio, and Stability Health; and he is supported by grants from the National Institutes of Health, PCORI and ADA.

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Nature Reviews Endocrinology thanks A. Ceriello, K. Kaku and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Klein, K.R., Buse, J.B. The trials and tribulations of determining HbA1c targets for diabetes mellitus. Nat Rev Endocrinol 16, 717–730 (2020). https://doi.org/10.1038/s41574-020-00425-6

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