Basal-bolus insulin may require fewer increases in daily doses than other insulin regimens

An observational trial compared insulin glargine once daily, biphasic insulin twice daily, and biphasic insulin three times daily with a basal-bolus regimen of rapid-acting insulin analogue three times daily and long-acting insulin once daily.


Basal-bolus insulin therapy allowed patients to maintain glycemic control similar to three other daily regimens but resulted in fewer increases in daily insulin doses, a study found.

Researchers investigated the association between four insulin regimens and increase in HbA1c or insulin dose in a real-life clinical setting among 757 patients with type 2 diabetes who had been treated with insulin for more than one year. Patient data were derived from a diabetes registry at Tenri Hospital, a regional tertiary care teaching hospital in Japan.

The insulin regimens compared in this observational study were:

  • regimen 1, insulin glargine once daily,
  • regimen 2, biphasic insulin twice daily,
  • regimen 3, biphasic insulin three times daily, and
  • regimen 4, rapid-acting insulin analogue three times daily and long-acting insulin once daily.

Main outcomes were increase in HbA1c level greater than 0.5%, increase in insulin dose, addition of oral antidiabetic drugs, and weight gain, all measured at one year. HbA1c levels, total daily insulin doses, doses of concomitant oral antidiabetic drugs, body weight, and body mass index were evaluated at baseline and one year. Results were published by the Journal of Diabetes Investigation on May 11.

At baseline the mean HbA1c level was 7.8% and duration of insulin therapy was 11.3 years. There were no significant differences among the regimens in the proportion of patients having their HbA1c level increase by more than 0.5% (22.8%, 24.9%, 20.7%, and 29.3% with regimens 1, 2, 3, and 4, respectively). However, a daily insulin dose increase was significantly less common among patients on regimen 4 at 38.6%, compared to 62.3%, 68.8%, and 65.3% of those on regimens 1, 2, and 3, respectively (P<0.001 for comparisons to regimen 4). Patients who received regimen 4 had significantly lower odds of requiring future insulin dose increases than those who had received regimen 2 (adjusted odds ratio, 0.24; 95% CI, 0.14 to 0.41; P<0.001).

Researchers found that an increase in insulin dose was less likely with regimen 4 compared with other regimens. “This may be because a basal-bolus therapy has [the] largest number of injections, which enables precise and subtle adjustment of insulin doses supported by and based on results of [self-monitoring of blood glucose] … The current study provides insights on real life clinical scenario and reminds us of the importance of the basal-bolus therapy,” they wrote.

One downside of regimen 4 was that patients prescribed neutral protamine Hagedorn had significant increases in body weight and were somewhat more likely to experience severe hypoglycemic events (although the difference was not statistically significant) compared with those prescribed insulin analogues (neutral protamine lispro, detemir and glargine). A target HbA1c level of 6.9% or lower was achieved in only 20% to 30% of patients on each regimen, the authors also noted.