Insulin Degludec Beats Sitagliptin in Type 2 Diabetes

BERLIN – Adding insulin degludec to an existing oral antidiabetes regimen produced significantly better glycemic control than did adding sitagliptin in the first head-to-head trial of the two drug classes in patients with type 2 diabetes.

After 26 weeks, patients who received insulin degludec as part of their regimen had an average 0.43% added reduction in their hemoglobin A_1c level, compared with patients on sitagliptin, a dipeptidyl peptidase 4 (DDP-4) inhibitor, in a multicenter, randomized study with 447 patients, Dr. Athena Philis-Tsimikas said at the meeting.

The main downside of the degludec regimen was an increased incidence of hypoglycemic episodes, with a 43% rate of confirmed hypoglycemic events among patients on insulin compared with a 13% rate among those who got sitagliptin. But just one degludec patient had a severe hypoglycemic event (none occurred among patients in the sitagliptin arm), said Dr. Philis-Tsimikas, an endocrinologist and chief medical officer at the Scripps Whittier Diabetes Institute in La Jolla, Calif.

Novo Nordisk, the company developing insulin degludec, currently has an application for approval of the drug pending with the Food and Drug Administration. Earlier this year, the company said that an FDA advisory committee was scheduled to consider the application in November. The data reported by Dr. Philis-Tsimikas forms part of the application.

"The results say that if a patient is failing [antidiabetes treatment] on one or two oral drugs, and their [Hb]A_1c is considerably below 9%, then a DDP-4 inhibitor is reasonable, but for efficacy insulin is probably a better choice," commented Dr. John L. Leahy, a professor and co-director of the division of endocrinology, diabetes, and metabolism at the University of Vermont in Colchester.

"Sitagliptin is a good comparator because when patients fail on one or two oral drugs the decision is often whether to add another oral drug or treat with insulin," Dr. Leahy said in an interview. "Some physicians then use a DPP-4 inhibitor, possibly inappropriately because the patient hemoglobin A_1c level is too high and the DDP-4 is not powerful enough. The message should go out to prescribing physicians that a DPP-4 inhibitor is not going to get your patient to goal unless their [Hb]A_1c is considerably lower than 9%."

The study enrolled patients with type 2 diabetes never previously treated with insulin whose HbA_1c levels remained at or above 7.5% despite treatment with one or two oral antidiabetes drugs for at least 3 months. The patients averaged about 56 years old, their average body mass index was about 30 kg/m², and their average HbA_1c at enrollment was about 9%. The researchers randomized patients to received 100 mg/day sitagliptin, or insulin degludec starting at a daily dosage of 10 U and titrated to achieve a prebreakfast plasma glucose of 4.0-4.9 mmol/L (71-89 mg/dL). Patients received insulin degludec once a day; they could choose the time of day to take their insulin, and although they had to keep to their dosing schedule they had the option to change their time of daily insulin treatment during the study.

After 26 weeks, the average HbA_1c level fell by about 1.6% in the 225 insulin-treated patients and by about 1.15% in the 222 sitagliptin-treated patients, an average difference in the amount of reduction of 0.43% that was statistically significant for the study’s primary end point. Treatment with insulin degludec led to an average reduction of fasting plasma glucose of 2.17 mmol/L compared with the reduction in the sitagliptin arm.

In addition to causing more hypoglycemic events, treatment with insulin degludec also produced an average weight gain of about 2.5 kg, compared with a slight weight loss in the sitagliptin-treated patients. Overall, treatment with insulin degludec produced an average 2.75 kg increase in weight compared with sitagliptin, a statistically significant difference. The incidence of all other adverse events was similar in the two treatment groups.

The study was sponsored by Novo Nordisk, the company that is developing insulin degludec. Dr. Philis-Tsimikas said that she has been an adviser to and speaker for and has received research funding from Novo Nordisk and from several other drug companies. Dr. Leahy said that he has been an adviser to Novo Nordisk and Merck.

BERLIN – Adding insulin degludec to an existing oral antidiabetes regimen produced significantly better glycemic control than did adding sitagliptin in the first head-to-head trial of the two drug classes in patients with type 2 diabetes.

After 26 weeks, patients who received insulin degludec as part of their regimen had an average 0.43% added reduction in their hemoglobin A_1c level, compared with patients on sitagliptin, a dipeptidyl peptidase 4 (DDP-4) inhibitor, in a multicenter, randomized study with 447 patients, Dr. Athena Philis-Tsimikas said at the meeting.

The main downside of the degludec regimen was an increased incidence of hypoglycemic episodes, with a 43% rate of confirmed hypoglycemic events among patients on insulin compared with a 13% rate among those who got sitagliptin. But just one degludec patient had a severe hypoglycemic event (none occurred among patients in the sitagliptin arm), said Dr. Philis-Tsimikas, an endocrinologist and chief medical officer at the Scripps Whittier Diabetes Institute in La Jolla, Calif.

Novo Nordisk, the company developing insulin degludec, currently has an application for approval of the drug pending with the Food and Drug Administration. Earlier this year, the company said that an FDA advisory committee was scheduled to consider the application in November. The data reported by Dr. Philis-Tsimikas forms part of the application.

"The results say that if a patient is failing [antidiabetes treatment] on one or two oral drugs, and their [Hb]A_1c is considerably below 9%, then a DDP-4 inhibitor is reasonable, but for efficacy insulin is probably a better choice," commented Dr. John L. Leahy, a professor and co-director of the division of endocrinology, diabetes, and metabolism at the University of Vermont in Colchester.

"Sitagliptin is a good comparator because when patients fail on one or two oral drugs the decision is often whether to add another oral drug or treat with insulin," Dr. Leahy said in an interview. "Some physicians then use a DPP-4 inhibitor, possibly inappropriately because the patient hemoglobin A_1c level is too high and the DDP-4 is not powerful enough. The message should go out to prescribing physicians that a DPP-4 inhibitor is not going to get your patient to goal unless their [Hb]A_1c is considerably lower than 9%."

The study enrolled patients with type 2 diabetes never previously treated with insulin whose HbA_1c levels remained at or above 7.5% despite treatment with one or two oral antidiabetes drugs for at least 3 months. The patients averaged about 56 years old, their average body mass index was about 30 kg/m², and their average HbA_1c at enrollment was about 9%. The researchers randomized patients to received 100 mg/day sitagliptin, or insulin degludec starting at a daily dosage of 10 U and titrated to achieve a prebreakfast plasma glucose of 4.0-4.9 mmol/L (71-89 mg/dL). Patients received insulin degludec once a day; they could choose the time of day to take their insulin, and although they had to keep to their dosing schedule they had the option to change their time of daily insulin treatment during the study.

After 26 weeks, the average HbA_1c level fell by about 1.6% in the 225 insulin-treated patients and by about 1.15% in the 222 sitagliptin-treated patients, an average difference in the amount of reduction of 0.43% that was statistically significant for the study’s primary end point. Treatment with insulin degludec led to an average reduction of fasting plasma glucose of 2.17 mmol/L compared with the reduction in the sitagliptin arm.

In addition to causing more hypoglycemic events, treatment with insulin degludec also produced an average weight gain of about 2.5 kg, compared with a slight weight loss in the sitagliptin-treated patients. Overall, treatment with insulin degludec produced an average 2.75 kg increase in weight compared with sitagliptin, a statistically significant difference. The incidence of all other adverse events was similar in the two treatment groups.

The study was sponsored by Novo Nordisk, the company that is developing insulin degludec. Dr. Philis-Tsimikas said that she has been an adviser to and speaker for and has received research funding from Novo Nordisk and from several other drug companies. Dr. Leahy said that he has been an adviser to Novo Nordisk and Merck.

BERLIN – Adding insulin degludec to an existing oral antidiabetes regimen produced significantly better glycemic control than did adding sitagliptin in the first head-to-head trial of the two drug classes in patients with type 2 diabetes.

After 26 weeks, patients who received insulin degludec as part of their regimen had an average 0.43% added reduction in their hemoglobin A_1c level, compared with patients on sitagliptin, a dipeptidyl peptidase 4 (DDP-4) inhibitor, in a multicenter, randomized study with 447 patients, Dr. Athena Philis-Tsimikas said at the meeting.

The main downside of the degludec regimen was an increased incidence of hypoglycemic episodes, with a 43% rate of confirmed hypoglycemic events among patients on insulin compared with a 13% rate among those who got sitagliptin. But just one degludec patient had a severe hypoglycemic event (none occurred among patients in the sitagliptin arm), said Dr. Philis-Tsimikas, an endocrinologist and chief medical officer at the Scripps Whittier Diabetes Institute in La Jolla, Calif.

Novo Nordisk, the company developing insulin degludec, currently has an application for approval of the drug pending with the Food and Drug Administration. Earlier this year, the company said that an FDA advisory committee was scheduled to consider the application in November. The data reported by Dr. Philis-Tsimikas forms part of the application.

"The results say that if a patient is failing [antidiabetes treatment] on one or two oral drugs, and their [Hb]A_1c is considerably below 9%, then a DDP-4 inhibitor is reasonable, but for efficacy insulin is probably a better choice," commented Dr. John L. Leahy, a professor and co-director of the division of endocrinology, diabetes, and metabolism at the University of Vermont in Colchester.

"Sitagliptin is a good comparator because when patients fail on one or two oral drugs the decision is often whether to add another oral drug or treat with insulin," Dr. Leahy said in an interview. "Some physicians then use a DPP-4 inhibitor, possibly inappropriately because the patient hemoglobin A_1c level is too high and the DDP-4 is not powerful enough. The message should go out to prescribing physicians that a DPP-4 inhibitor is not going to get your patient to goal unless their [Hb]A_1c is considerably lower than 9%."

The study enrolled patients with type 2 diabetes never previously treated with insulin whose HbA_1c levels remained at or above 7.5% despite treatment with one or two oral antidiabetes drugs for at least 3 months. The patients averaged about 56 years old, their average body mass index was about 30 kg/m², and their average HbA_1c at enrollment was about 9%. The researchers randomized patients to received 100 mg/day sitagliptin, or insulin degludec starting at a daily dosage of 10 U and titrated to achieve a prebreakfast plasma glucose of 4.0-4.9 mmol/L (71-89 mg/dL). Patients received insulin degludec once a day; they could choose the time of day to take their insulin, and although they had to keep to their dosing schedule they had the option to change their time of daily insulin treatment during the study.

After 26 weeks, the average HbA_1c level fell by about 1.6% in the 225 insulin-treated patients and by about 1.15% in the 222 sitagliptin-treated patients, an average difference in the amount of reduction of 0.43% that was statistically significant for the study’s primary end point. Treatment with insulin degludec led to an average reduction of fasting plasma glucose of 2.17 mmol/L compared with the reduction in the sitagliptin arm.

In addition to causing more hypoglycemic events, treatment with insulin degludec also produced an average weight gain of about 2.5 kg, compared with a slight weight loss in the sitagliptin-treated patients. Overall, treatment with insulin degludec produced an average 2.75 kg increase in weight compared with sitagliptin, a statistically significant difference. The incidence of all other adverse events was similar in the two treatment groups.

The study was sponsored by Novo Nordisk, the company that is developing insulin degludec. Dr. Philis-Tsimikas said that she has been an adviser to and speaker for and has received research funding from Novo Nordisk and from several other drug companies. Dr. Leahy said that he has been an adviser to Novo Nordisk and Merck.