Clinical Health Updates

Basal insulin less effective, better tolerated than biphasic and prandial

Clinical Question:
Which is preferred — biphasic, prandial, or basal insulin — for patients with poorly controlled Type 2 diabetes mellitus?

Bottom Line:
Patients choosing biphasic or prandial insulin regiments should be prepared to gain approximately 10 pounds to 12 pounds and expect 4 to 8 moderate or severe episodes of hypoglycemia per year. Basal insulin was a bit less effective as measured by the change in glycated hemoglobin (Hb A1C), but resulted in less weight gain and much less hypoglycemia. Of course, we don’t know whether any of these regiments improve long-term clinical outcomes in these patients. If you are going to add insulin for a patient with poorly controlled Type 2 diabetes, it makes sense to start with a single dose of basal insulin for most patients, and to focus primarily on those patients with an initial Hb A1C of more than 8.5%.

Holman RR, Thorne KI, Farmer AJ, et al, for the 4-T Study Group. Addition of biphasic, prandial or basal insulin to oral therapy in Type 2 diabetes. N Engl J Med 2007;357(17):1716-1730.

Study Design:
Randomized controlled trial (nonblinded)

Adding insulin to oral therapy in type 2 diabetes mellitus is customary when glycemic control is suboptimal, though evidence supporting specific insulin regimens is limited. In an open-label, controlled, multicenter trial, we randomly assigned 708 patients with a suboptimal glycated hemoglobin level (7.0 to 10.0%) who were receiving maximally tolerated doses of metformin and sulfonylurea to receive biphasic insulin aspart twice daily, prandial insulin aspart three times daily, or basal insulin detemir once daily (twice if required). Outcome measures at 1 year were the mean glycated hemoglobin level, the proportion of patients with a glycated hemoglobin level of 6.5% or less, the rate of hypoglycemia, and weight gain. At 1 year, mean glycated hemoglobin levels were similar in the biphasic group (7.3%) and the prandial group (7.2%) (P=0.08) but higher in the basal group (7.6%, P<0.001 for both comparisons). The respective proportions of patients with a glycated hemoglobin level of 6.5% or less were 17.0%, 23.9%, and 8.1%; respective mean numbers of hypoglycemic events per patient per year were 5.7, 12.0, and 2.3; and respective mean weight gains were 4.7 kg, 5.7 kg, and 1.9 kg. Rates of adverse events were similar among the three groups.