EASD: Insulin Detemir (Levemir) Provides Good Control Long Term

September 21, 2007

AMSTERDAM -- Patients with type 1 diabetes who used insulin detemir (Levemir) for two years had better glycemic control and less nocturnal hypoglycemia than patients on NPH insulin, investigators reported here.

AMSTERDAM, Sept. 21 -- Patients with type 1 diabetes who used insulin detemir (Levemir) for two years had better glycemic control and less nocturnal hypoglycemia than patients on NPH insulin, investigators reported here.

A study of nearly 500 men and women showed that patients on insulin detemir had greater reductions in glycosylated hemoglobin A1c (HbA1c) levels at study end, and a significantly greater number of patients on detemir had HbA1c levels below 7% in the last month of the study, Paul Bartley, M.B. of the University of Queensland in Stones Corner, Australia, reported at the European Association for the Study of Diabetes meeting.

A second study--the 5,604-patient PREDICTIVE 303 trial-also reported at the meeting, found that patients with type 2 diabetes who self-titrated insulin detemir achieved better glycemic control than patients whose doses were titrated by physicians.

In PREDICTIVE 303 (Predictable Results and Experience in Diabetes through Intensification and Control to Target: an International Variability Evaluation), patients with higher baseline BMI (30 to more than 40 kg/m2) achieved a slight, but not statistically significant, weight loss.

"The benefits of insulin detemir found in previous short-term studies of basal bolus treatment in type 1 diabetes were confirmed in this two year study," said Dr. Bartley.

"We believe that this type of insulin answers two of the major difficulties found in the Diabetes Control of Complications Trial [DCCT], namely the block to better treatment of hypoglycemia and weight gain," he said. "Certainly in this trial we have reduced the hypoglycemia quite dramatically"

The study was a 24-month, multi-national, open-label, parallel group trial comparing long-term efficacy and safety of insulin detemir and NPH insulin in combination with mealtime insulin aspart, using a treat-to-target protocol.

A total of 497 men and women with a mean age of 35 and mean duration of diabetes of 13 years were enrolled in the study. The patients were comparatively lean, with a mean BMI of 24.7 kg/m2. The mean HbA1c level at baseline was 8.3%.

The patients were randomized in a 2:1 ratio to receive either insulin detemir (331 patients) or NPH (166 patients) and were instructed to administer basal insulin once daily, in the evening.

Insulin doses were individually titrated based on patient self-monitoring of blood glucose, aiming for pre-breakfast and pre-dinner plasma glucose targets of 6.0 mmol/L (108 mg/dL) or lower.

A second basal morning dose would be added if the average fasting plasma glucose was 6.0 mmol/L but the average pre-dinner plasma glucose remained 6.0 mmol/L or greater even after optimization of the evening and bolus insulin doses.

The authors found that, after two years, the mean HbA1c levels were significantly lower among the patients in the detemir group, at 7.36%, compared with 7.58% for the NPH group (mean difference -0.22%, 95% confidence interval -0.41 to -0.03%).

The reductions from baseline means were 0.9 percentage points for detemir, and 0.7 points for NPH.

In addition, during the last month of treatment, 22% of patients on detemir had HbA1cs below 7%, the American Diabetes Association target. That level was reached by only 13% of patients on NPH (P=0.019).

Patients on detemir also had a 69% lower relative risk of 24-hour major hypoglycemia (P

However, there were more withdrawals because of adverse events among patients on detemir, 3.9% compared with 0.6% for NPH.

In the PREDICTIVE study, patients with type 2 diabetes were instructed how to titrate their own basal insulin dose based on three days of self-monitored fasting plasma glucose levels using a simple algorithm, and the results were compared with those of physician-titrated doses.

"I think there's growing evidence that patient self-adjustment of the basal insulin dose offers an opportunity to better affect therapy, said Luigi Meneghini, M.D., of the University of Miami, the study's lead author.

"The use of detemir in this predominantly primary care setting resulted in significant improvements in glycemic control without weight gain in the overall population," he continued. "The simplified patient-driven titration algorithm appears to be safe and effective compared to physician-driven insulin dose adjustments."