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Basal-Bolus Versus Once, Twice, and Even Three Times A Day of Long-Acting Insulin

Research compares health outcomes in four insulin regimens.

Satoru Tsujii, MD, PhD, of the department of endocrinology at Tenri Hospital in Japan, and colleagues evaluated data from the Diabetes Distress and Care Registry on 757 adults (mean age, 65.7 years) with type 2 diabetes (mean HbA1c level, 7.8%; mean duration of insulin therapy, 11.3 years) who presented to Tenri Hospital to determine the association between four insulin regimens and increases in HbA1c and insulin dose.

They investigated the association between four insulin regimens and increase in HbA1c and insulin dose in a real-life clinical setting because there is no data about them among insulin regimens.

Subjects included 757 patients with type 2 diabetes having been treated with insulin therapy for more than 1 year. The four insulin regimens were regimen 1 (long-acting insulin, once daily), regimen 2 (biphasic insulin, twice daily), regimen 3 (biphasic insulin, three times daily), and regimen 4 (basal-bolus therapy). Main outcomes were increases in HbA1c levels >0.5% and increases in daily insulin units after 1 year. They performed multivariable analyses to examine differences in glycemic control and insulin dose with adjustment for possible confounders.

Increased HbA1c at the end of follow-up was significantly associated with age and higher HbA1c level at baseline. Odds of increasing daily insulin units 1 year later were significantly lower in participants on regimen 4 compared with participants on regimen 2. “Regardless of the insulin regimen used, a considerable number of patients treated with insulin therapy showed increases in both HbA1c levels and insulin doses at the end of follow-up,” the researchers wrote. “These findings indicate the limitations and unmet needs of current insulin regimens. Multivariable regression analysis showed that patients who received regimen 4 had the smallest odds of requiring future insulin dose increases. 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 blood glucose, eventually little increase in total daily doses.

Current study reveals that that those on basal-bolus therapy had significantly lower odds of increasing daily insulin units one year after their regimen than those on biphasic insulin twice daily. The results showed that the mean HbA1c level and duration of insulin therapy were 7.8% and 11.3 years, respectively. HbA1c levels increased by >0.5% at follow-up in 22.8%, 24.9%, 20.7%, and 29.3% of subjects using regimen 1, 2, 3, and 4, respectively, with no significant differences between groups. Daily insulin doses increased in 62.3%, 68.8%, 65.3%, and 38.6% of patients, respectively (P<0.001). Multivariable regression analysis showed that patients who received regimen 4 had significantly lower odds of requiring future insulin dose increases than those who had received regimen 2. (P<0.001).

From the results, it was concluded that many patients receiving insulin therapy showed increases in HbA1c levels and insulin doses 1 year later. The smallest increase in insulin dose was observed in the basal-bolus therapy group compared with other regimens.

Practice Pearls:

  • Adults with type 2 diabetes assigned to basal-bolus therapy require a smaller increase in insulin dose after 1 year compared with adults assigned to long-acting insulin or biphasic insulin,
  • The smallest increase in insulin dose was observed in the basal-bolus therapy group compared with other regimens.
  • The researchers found that 29.3% of type 2 diabetes patients on basal-bolus therapy had an A1C increase of more than 0.5%, compared with 22.8% of those on once-daily long-acting insulin, 24.9% on twice-daily biphasic insulin and 20.7% on biphasic insulin three times daily.

The findings are in the Journal of Diabetes Investigation, 11 May 2017