#81 Type 2 Diabetes and A1c targets: Pragmatic dogma
CLINICAL QUESTION
What are reasonable Hemoglobin A1c (A1c) targets for our patients with Type 2 Diabetes Mellitus?
BOTTOM LINE
While many patients can safely attain an A1c at or just below 7%, older patients, those with long-standing diabetes, multiple co-morbidities, and/or high risk of hypoglycemia, reasonable targets are perhaps 7-8% or even higher.
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EVIDENCE
Intense management of blood glucose in Type 2 Diabetes examined in ≥ ten meta-analyses. 1-10
- Studies varied in ages, co-morbidities, medications, etc., making evidence interpretation and application more difficult.
- Newly diagnosed diabetics, age ~50’s, few co-morbidities, receiving single glucose lowering therapy (to start) versus diet.
- UKPDS 33: 3,867 patients, sulfonylurea or insulin (median ten year A1c 7.0% versus 7.9%).11
- Over ten years, significant reduction in death Number Needed to Treat (NNT)=29 and myocardial infarction (MI) NNT=36. 12
- UKPDS 34: 753 patients, metformin (median ten year A1c 7.4% versus 8.0%). 13
- Over ten years, significant reduction in death NNT=14 and MI NNT=16. 12
- UKPDS 33: 3,867 patients, sulfonylurea or insulin (median ten year A1c 7.0% versus 7.9%).11
- Older, established diabetics, age ~60’s, more co-morbidities, receiving multiple glucose-lowering therapies (to start) for intense versus conventional.
- ACCORD:14 10,251 patients, x3.5 years, AIC 6.4% versus 7.5%.
- ADVANCE:15 11,140 patients, x5 years, A1C 6.5% versus 7.3%.
- Veterans:16 1,791 patients, x5.6 years, A1C 6.9% versus 8.4%.
- Intense management led to:
- Microvascular improvement:17 Prevented visual deterioration (three lines worse on Snellen chart) NNT=60 and loss of light touch sensation NNT=49.
- No benefit in cardiovascular outcomes14-16 except one study found reduced non-fatal MI NNT=100. 15
- Inconsistently worse: mortality in one study14 Number Needed to Harm (NNH)=96 and hospitalization in another15 NNH=48.
- Consistently worse:14-16 Weight gain (gain ≥10kg14 NNH=8), and hypoglycemia (severe requiring medical assistance NNH=15).
- New US-European Guidelines18 recommend less stringent targets in patients with longer disease duration, shorter life expectancy, increased co-morbidities, and high risk of hypoglycemia or other adverse events.
- Cohort data indicates that in established diabetics, A1c of 7.5% may have the lowest mortality.19
- Macrovascular complications such as cardiovascular events are much more common than end-stage microvascular endpoints such as progression to dialysis or blindness.11,20
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