Evidence of the Month

1
Evidence of the Month
Jens Sandahl Christiansen

• Comment on
• Addition of biphasic, prandial, or basal insulin
  to oral therapy in type 2 diabetes

Investigators Holman RR, Thorne KI, Farmer AJ,
et al, for the 4-T Study Group Published N Engl
J Med. 20073571716-1730
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Methods/primary outcome

• Goals Reporting of the 1-year results of the
  4-T study
• Design 4-T is a 3-year, open-label, controlled
  study comparing different insulin formulations
  and titration algorithms
• Patients randomized to 1 of 3 insulin therapies
  
• Basal insulin detemir once or twice daily
• Prandial insulin aspart 3 times daily
• Biphasic insulin aspart twice daily
• Patients 708 adults with Type 2 diabetes
  from 58 centres in Ireland and the United Kingdom
• Sample Suboptimal glycaemic control with
  metformin and sulfonylurea for at least 4 months
  prior to screening
• Outcome HbA1c level at 1 year

.
4-TTreating to Target in Type 2 Diabetes
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Change in HbA1c over 1 year
Baseline to 1 year ()
Mean SD at 1 year ()
Biphasic 7.30.9 1.31.1 Prandial 7.20.9,
P0.08 vs biphasic 1.41.0 Basal
7.61.0, Plt0.001 vs biphasic or prandial
0.81.0
Biphasic Prandial Basal
Glycated haemoglobin ()
Months since randomization
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Change in body weight over 1 year
Baseline to 1 year (kg)
Biphasic 4.74.0 Prandial 5.74.6, P0.005 vs
biphasic Basal 1.94.2, Plt0.001 vs biphasic or
prandial
Biphasic Prandial Basal
Body weight (kg)

Months since randomization
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Hypoglycaemic events

• Superiority in glycaemic control with prandial
  and biphasic insulin came at a cost of increased
  hypoglycaemic events
• 12.0 events per patient per year with prandial
  insulin, 5.7 with biphasic insulin, and 2.3 with
  basal insulin

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Clinical implications

• Addition of insulin therapy, irrespective of mode
  chosen, to oral antidiabetic regimen will
  significantly improve glycaemic control and
  should be initiated early
• A long-acting insulin analogue alone is often
  insufficient to get patients to target (HbA1c
  lt7.0 or lt6.5)
• Addition of a rapid-acting insulin is superior to
  basal insulin alone in getting patients to target
• Choice between biphasic and bolus insulin depends
  on patients ability to handle complex regimen,
  but some patients also need prandial insulin at
  lunchtime
• Biphasic or prandial insulin increases frequency
  of hypoglycaemia stopping insulin secretagogues
  may help to reduce hypoglycaemic events
• Cessation of sulfonylurea should be considered
  when starting insulin therapy