Type 2 diabetes and hemoglobin A_1c targets

Clinical question

What are reasonable hemoglobin A_1c (HbA_1c) targets for patients with type 2 diabetes mellitus?

Bottom line

While many patients safely attain HbA_1c levels at or just below 7%, for older patients with long-standing diabetes, multiple comorbidities, and high risk of hypoglycemia, reasonable targets are 7% to 8% or higher.

Evidence

Intense management of blood glucose in type 2 diabetes was examined in 10 meta-analyses.¹

• Patients varied by age, comorbidities, medications, etc, making evidence interpretation and application difficult. Five reasonably sized trials fall into 2 groups:

• Patients in their 50s newly diagnosed with diabetes with few comorbidities randomized to 1 glucose-lowering therapy or diet control, followed for about 17 years (outcomes reported as 10-year rates).

  • -UKPDS 33 (N = 3867): sulfonylurea or insulin (HbA_1c 7.0% vs 7.9%).²

    • —Reduction in death (NNT = 29; P = .007) and myocardial infarction (MI) (NNT = 36; P = .01).³
  • -UKPDS 34 (N = 753): metformin (HbA_1c 7.4% vs 8.0%).⁴

    • —Reduction in death (NNT = 14; P = .002) and MI (NNT = 16; P = .005).³
• Patients with established diabetes in their 60s with more comorbidities receiving multiple glucose-lowering therapies for intense versus conventional therapy.

  • -ACCORD⁵ (N = 10 251): 3.5 years, HbA_1c 6.4% versus 7.5%.
  • -ADVANCE⁶ (N = 11 140): 5 years, HbA_1c 6.5% versus 7.3%.
  • -Veterans⁷ (N = 1791): 5.6 years, HbA_1c 6.9% versus 8.4%.
  • -Intense management led to prevention of visual deterioration (NNT = 60) and loss of light-touch sensation (NNT = 49)⁸; no benefit in CV outcomes^5–7 except reduced nonfatal MI in 1 study (NNT = 100)⁶; worsening mortality⁵ (NNH = 96) and hospitalization⁶ (NNH = 48); and weight gain (1 in 8 gained ≥ 10 kg⁵) and hypoglycemia (severe⁵; NNH = 15).^5–7

Context

• Cohort data indicate that

  • -in patients with established diabetes, HbA_1c of 7.5% might have the lowest mortality⁹; and
  • -in elderly patients requiring assistance, HbA_1c levels less than 7% had the highest risk of worsening function and HbA_1c levels of 8% to 9% had the lowest risk.¹⁰

• Macrovascular complications are more common than end-stage microvascular end points.^2,11

Implementation

New guidelines^12,13 recommend less stringent targets (eg, 7.1% to 8.5%) in patients with shorter life expectancy, increased comorbidities, increased functional dependency, and high risk of hypoglycemia or other adverse events. In elderly patients with diabetes with HbA_1c of 7.0% or lower, reduction of diabetic medications for modest HbA_1c control addresses risk of hypoglycemia, polypharmacy, falls, functional decline, adverse cardiovascular outcomes, and mortality. First steps include reducing insulin or sulfonylureas to minimize hypoglycemia risk, or reducing thiazolidinediones to minimize heart failure or fracture risk. As targets and therapy are individualized, HbA_1c targets of 7% or lower as quality indicators should be reconsidered.

Tools for Practice articles in Canadian Family Physician (CFP) are adapted from articles published on the Alberta College of Family Physicians (ACFP) website, summarizing medical evidence with a focus on topical issues and practice-modifying information. The ACFP summaries and the series in CFP are coordinated by Dr G. Michael Allan, and the summaries are co-authored by at least 1 practising family physician and are peer reviewed. Feedback is welcome and can be sent to toolsforpractice@cfpc.ca. Archived articles are available on the ACFP webte: www.acfp.ca.