Novel insulin analogue combo misses noninferiority endpoint

VIENNA – A novel fixed-dose insulin analogue combination reduced blood glucose levels to a similar degree as a control basal-bolus regimen in patients with type 2 diabetes but just failed to show noninferiority for the primary endpoint in a phase IIIb randomized trial.

The percentage change in hemoglobin A_1c from baseline to week 26 was –1.3% for IDegAsp (Ryzodeg, Novo Nordisk) and –1.5% for the basal-bolus regimen used as the comparator.

IDegAsp is a soluble combination of 70% insulin degludec (Tresiba, Novo Nordisk) and 30% insulin aspart (NovoLog, Novo Nordisk). Unlike other fixed-dose insulins, IDeg and IAsp exist separately in a coformulation.

Although noninferiority was not demonstrated for glycemic control, there was a significant benefit in terms of a lower dose of insulin used (1.11 vs. 1.34 U) and less weight gain, of about 1 kg, with IDegAsp than with the basal-bolus approach. There were also numerically lower rates of confirmed (rate ratio, 0.81) and nocturnal hypoglycemia (RR, 0.80). Both regimens were well tolerated.

“If we are very, very, strict, and as we did not reach noninferiority, we can’t really say anything about anything else,” study investigator Dr. John Cooper of Stavanger (Norway) University Hospital conceded in an interview at the annual meeting of the European Association for the Study of Diabetes. He added, however, “common sense says that it is very close and it looks like it is a useful insulin.”

Patients with type 2 diabetes of at least 6 months duration and who had an HbA_1c of 7%-10% despite being treated with basal insulin with or without oral antidiabetic drugs for at least 3 months were eligible for inclusion in the study.

In all, 274 patients were included, with 138 randomized to twice-daily treatment with IDegAsp and 136 to IDeg once daily plus IAsp two to four times a day. The mean age of the participants was 60 years, the mean HbA_1c at baseline was 8.3%, and the average duration of diabetes was 13 years. The majority (63%) of patients had been treated with insulin glargine prior to study entry.

“IDegAsp twice daily may represent a simple alternative to basal-bolus treatment in patients who require intensification of basal insulin regimens, especially when adherence to more complex regimens is challenging,” Dr. Cooper said at the conclusion of his presentation.

He noted during the discussion that quality of life had been assessed using the Short-Form 36 at the start and end of the trial, and while there were no differences between the regimens in terms of the physical scores, there was a benefit seen in the mental component with IDegAsp that was driven mainly by improvements in social functioning.

“I’ve mainly used basal plus meal-time insulin doses in type 2 diabetes patients, but I might reconsider using the combination, but that’s more on the basis that I know it gives less hypoglycemia, compared with the older, premixed insulins,” Dr. Cooper commented in the postpresentation interview.

The novel insulin formulation could also offer patients who need treatment intensification a more convenient approach to their insulin therapy, he said, rather than having to inject long-acting insulin once daily and short-acting insulin up to four times a day. With IDegAsp, patients could inject just twice a day at major meal times. “This will certainly be a useful addition for some patients,” Dr. Cooper suggested.

To date, IDegAsp has been approved for use in several European, Asian, and South American countries. The Food and Drug Administration, however, has requested additional cardiovascular outcomes data to be obtained before giving market authorization for its use.

The study was funded by Novo Nordisk. Dr. Cooper has received research support and speaker fees from Novo Nordisk, Sanofi, Eli Lilly and Company, Merck, and AstraZeneca, and is a member of a speakers bureau for Novartis.

VIENNA – A novel fixed-dose insulin analogue combination reduced blood glucose levels to a similar degree as a control basal-bolus regimen in patients with type 2 diabetes but just failed to show noninferiority for the primary endpoint in a phase IIIb randomized trial.

The percentage change in hemoglobin A_1c from baseline to week 26 was –1.3% for IDegAsp (Ryzodeg, Novo Nordisk) and –1.5% for the basal-bolus regimen used as the comparator.

IDegAsp is a soluble combination of 70% insulin degludec (Tresiba, Novo Nordisk) and 30% insulin aspart (NovoLog, Novo Nordisk). Unlike other fixed-dose insulins, IDeg and IAsp exist separately in a coformulation.

Although noninferiority was not demonstrated for glycemic control, there was a significant benefit in terms of a lower dose of insulin used (1.11 vs. 1.34 U) and less weight gain, of about 1 kg, with IDegAsp than with the basal-bolus approach. There were also numerically lower rates of confirmed (rate ratio, 0.81) and nocturnal hypoglycemia (RR, 0.80). Both regimens were well tolerated.

“If we are very, very, strict, and as we did not reach noninferiority, we can’t really say anything about anything else,” study investigator Dr. John Cooper of Stavanger (Norway) University Hospital conceded in an interview at the annual meeting of the European Association for the Study of Diabetes. He added, however, “common sense says that it is very close and it looks like it is a useful insulin.”

Patients with type 2 diabetes of at least 6 months duration and who had an HbA_1c of 7%-10% despite being treated with basal insulin with or without oral antidiabetic drugs for at least 3 months were eligible for inclusion in the study.

In all, 274 patients were included, with 138 randomized to twice-daily treatment with IDegAsp and 136 to IDeg once daily plus IAsp two to four times a day. The mean age of the participants was 60 years, the mean HbA_1c at baseline was 8.3%, and the average duration of diabetes was 13 years. The majority (63%) of patients had been treated with insulin glargine prior to study entry.

“IDegAsp twice daily may represent a simple alternative to basal-bolus treatment in patients who require intensification of basal insulin regimens, especially when adherence to more complex regimens is challenging,” Dr. Cooper said at the conclusion of his presentation.

He noted during the discussion that quality of life had been assessed using the Short-Form 36 at the start and end of the trial, and while there were no differences between the regimens in terms of the physical scores, there was a benefit seen in the mental component with IDegAsp that was driven mainly by improvements in social functioning.

“I’ve mainly used basal plus meal-time insulin doses in type 2 diabetes patients, but I might reconsider using the combination, but that’s more on the basis that I know it gives less hypoglycemia, compared with the older, premixed insulins,” Dr. Cooper commented in the postpresentation interview.

The novel insulin formulation could also offer patients who need treatment intensification a more convenient approach to their insulin therapy, he said, rather than having to inject long-acting insulin once daily and short-acting insulin up to four times a day. With IDegAsp, patients could inject just twice a day at major meal times. “This will certainly be a useful addition for some patients,” Dr. Cooper suggested.

To date, IDegAsp has been approved for use in several European, Asian, and South American countries. The Food and Drug Administration, however, has requested additional cardiovascular outcomes data to be obtained before giving market authorization for its use.

The study was funded by Novo Nordisk. Dr. Cooper has received research support and speaker fees from Novo Nordisk, Sanofi, Eli Lilly and Company, Merck, and AstraZeneca, and is a member of a speakers bureau for Novartis.

VIENNA – A novel fixed-dose insulin analogue combination reduced blood glucose levels to a similar degree as a control basal-bolus regimen in patients with type 2 diabetes but just failed to show noninferiority for the primary endpoint in a phase IIIb randomized trial.

The percentage change in hemoglobin A_1c from baseline to week 26 was –1.3% for IDegAsp (Ryzodeg, Novo Nordisk) and –1.5% for the basal-bolus regimen used as the comparator.

IDegAsp is a soluble combination of 70% insulin degludec (Tresiba, Novo Nordisk) and 30% insulin aspart (NovoLog, Novo Nordisk). Unlike other fixed-dose insulins, IDeg and IAsp exist separately in a coformulation.

Although noninferiority was not demonstrated for glycemic control, there was a significant benefit in terms of a lower dose of insulin used (1.11 vs. 1.34 U) and less weight gain, of about 1 kg, with IDegAsp than with the basal-bolus approach. There were also numerically lower rates of confirmed (rate ratio, 0.81) and nocturnal hypoglycemia (RR, 0.80). Both regimens were well tolerated.

“If we are very, very, strict, and as we did not reach noninferiority, we can’t really say anything about anything else,” study investigator Dr. John Cooper of Stavanger (Norway) University Hospital conceded in an interview at the annual meeting of the European Association for the Study of Diabetes. He added, however, “common sense says that it is very close and it looks like it is a useful insulin.”

Patients with type 2 diabetes of at least 6 months duration and who had an HbA_1c of 7%-10% despite being treated with basal insulin with or without oral antidiabetic drugs for at least 3 months were eligible for inclusion in the study.

In all, 274 patients were included, with 138 randomized to twice-daily treatment with IDegAsp and 136 to IDeg once daily plus IAsp two to four times a day. The mean age of the participants was 60 years, the mean HbA_1c at baseline was 8.3%, and the average duration of diabetes was 13 years. The majority (63%) of patients had been treated with insulin glargine prior to study entry.

“IDegAsp twice daily may represent a simple alternative to basal-bolus treatment in patients who require intensification of basal insulin regimens, especially when adherence to more complex regimens is challenging,” Dr. Cooper said at the conclusion of his presentation.

He noted during the discussion that quality of life had been assessed using the Short-Form 36 at the start and end of the trial, and while there were no differences between the regimens in terms of the physical scores, there was a benefit seen in the mental component with IDegAsp that was driven mainly by improvements in social functioning.

“I’ve mainly used basal plus meal-time insulin doses in type 2 diabetes patients, but I might reconsider using the combination, but that’s more on the basis that I know it gives less hypoglycemia, compared with the older, premixed insulins,” Dr. Cooper commented in the postpresentation interview.

The novel insulin formulation could also offer patients who need treatment intensification a more convenient approach to their insulin therapy, he said, rather than having to inject long-acting insulin once daily and short-acting insulin up to four times a day. With IDegAsp, patients could inject just twice a day at major meal times. “This will certainly be a useful addition for some patients,” Dr. Cooper suggested.

To date, IDegAsp has been approved for use in several European, Asian, and South American countries. The Food and Drug Administration, however, has requested additional cardiovascular outcomes data to be obtained before giving market authorization for its use.

The study was funded by Novo Nordisk. Dr. Cooper has received research support and speaker fees from Novo Nordisk, Sanofi, Eli Lilly and Company, Merck, and AstraZeneca, and is a member of a speakers bureau for Novartis.