Table 1

Trials of intensive versus less-intensive BG lowering: No RCTs studying the effects of intensive glycemic control have included frail elderly patients.

RCT TRIALMEAN AGE, YTRIAL DURATION, YHBA1C ATTAINED, %BENEFITS OR HARMS IN MORE-INTENSIVE GLUCOSE-LOWERING ARM (LOWER HBA1C) VS LESS-INTENSIVE TREATMENT ARM
UKPDS-33454107.0 vs 7.9

  • No difference in major clinical outcomes* at 10 y†

  • Benefits on surrogate outcomes (less microvascular disease after ≥ 6 y)

  • Increase in serious hypoglycemia

  • A follow-up study after 20 y saw decreased MI and all-cause death6

ADVANCE76656.5 vs 7.3

  • No difference in major clinical outcomes* at 5 y

  • Decrease in microvascular end points (NNT = 67 at 5 y), mostly nephropathy surrogates

  • Increase in serious hypoglycemia (NNH = 83 at 5 y)

VADT8 (most participants had a history of CV problems)605.66.9 vs 8.4

  • No difference in major clinical outcomes* at 5.6 y

  • Increased rate of serious adverse events (NNH = 15 at 5.6 y)

  • Increase in serious hypoglycemia (NNH = 83 at 5.6 y)

ACCORD9 (35% of participants had a history of CV problems)623.56.4 vs 7.5

  • More death with intensive treatment (NNH = 95 at 3.5 y) (any macrovascular benefit outweighed by increase in death)

  • Increase in serious hypoglycemia (NNH = 9 at 3.5 y)

  • ACCORD—Action to Control Cardiovascular Risk in Diabetes, ADVANCE—Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation, BG—blood glucose, CV–cardiovascular, HbA1c—glycated hemoglobin A1c, MI—myocardial infarction, NNT—number needed to treat for 1 additional person to benefit, NNH—number needed to treat for 1 additional person to be harmed, RCT—randomized controlled trial, T2DM—type 2 diabetes mellitus, UKPDS—United Kingdom Prospective Diabetes Study, VADT—Veterans Affairs Diabetes Trial.

  • ↵* Major clinical outcomes included CV death, MI, stroke, end-stage renal disease, and blindness.

  • ↵† The UKPDS-345 found a decrease in death (NNT = 14 at 10.7 y) and decrease in stroke (NNT = 48 at 10 y) when metformin specifically was used compared with standard treatment in obese patients with T2DM (HbA1c achieved was 7.4% vs 8.0%).