Liraglutide tested as add-on therapy for type 1 diabetes

LAS VEGAS – In patients with type 1 diabetes, adding a 1.8-mg daily dose of liraglutide to insulin significantly reduced hemoglobin A_1c, mean blood glucose, body weight, carbohydrate intake, and C-reactive protein, in a randomized study.

The 72-patient study also showed that adding liraglutide (Victoza) significantly improved quality of life and reduced systolic blood pressure in the groups that were receiving higher doses of the medicine.

Naseem Miller/Frontline Medical News

"Our findings have significant implications for the future treatment of type 1 diabetes," said Dr. Nitesh Kuhadiya of the State University of New York at Buffalo, who presented the findings at the annual meeting of the American Association of Clinical Endocrinologists. "Long term studies are needed to establish the durability of the effects."

In previous small, nonrandomized studies of patients with type 1 diabetes, liraglutide improved glycemic control and led to weight loss (Eur. J. Endocrinol. 2011;165:77-84; Endocr. Pract. 2013;19:963-7). They then decided to conduct a randomized controlled trial, which is the first of its kind, said Dr. Kuhadiya, who compared type 1 diabetes to a "wild horse that’s extremely difficult to tame and kicks you 10 times a day."

For the study, researchers randomized 72 patients to four groups to receive 0.6, 1.2, or 1.8 mg of liraglutide or a placebo daily for 12 weeks. One patient dropped out of placebo group, as well as five from the 1.2-mg and three from the 1.8-mg group.

The groups’ baseline characteristics were similar. All patients had type 1 diabetes for at least 1 year, were on insulin therapy, and had no detectable C-peptide in plasma. The mean age was 44 years, mean body weight was 83 kg, mean body mass index was 29 kg/m², mean HbA_1c was 7.5, and mean interval since diabetes diagnosis was 20 years. Nearly all (96%) patients were white and 56% were women.

There was a significant drop of nearly 10 mg/dL in average glucose in the 1.2- and 1.8-mg groups. The HbA_1c, also dropped in those two groups, although it was significant in only the 1.2-mg group, by about 0.8%. The drop was 0.4% in 1.8-mg group, 0.2% in the 0.6-mg group, and 0.3% in the placebo subjects.

There were also significant changes in the percent time spent in different glycemic thresholds for the 1.8-mg group. 

Patients on 1.2 mg and 1.8 mg of liraglutide spent about 3%-5% more time in the 70- to 160-mg/dL zone, respectively, although only those on 1.8 mg reached statistical significance. 

Again, the 1.2- and 1.8-mg groups spent less time in hyperglycemia, defined as 160-240 mg/dL, Dr. Kuhadiya said. No significant changes were observed in the other two groups. 

A similar trend was seen for severe hyperglycemia (250 mg/dL). 

There was, however, some additional hypoglycemia in the study in the range of 55 to 70 mg/dL, Dr. Kuhadiya reported. The 1.2- and 1.8-mg groups spent significantly more time (nearly 1%) in that range, but there was no incidence of hypoglycemia in the placebo and 0.6-mg groups. The results were similar for the less than 50 mg/dL range. However, there was no incidence of hypoglycemia requiring hospitalization or medical attention, Dr. Kuhadiya said. 

All three groups receiving liraglutide showed significant weight loss: nearly 5 kg in the 1.2- and 1.8-mg groups, and 3 kg in the 0.6-mg group, over a period of 12 weeks. 

The carbohydrate intake for the 1.2- and 1.8-mg groups also dropped significantly. 

Dr. Kuhadiya said that the findings also show that all changes are independent of each other. 

All groups showed a fall in C-reactive protein, which is a marker for cardiovascular risk, although only the 1.8-mg groups showed a statistical significance. "And this is important because most patients with type 1 diabetes have metabolic syndrome, and to be able to demonstrate all these changes and an additional fall in CRP means further protection from cardiovascular risk," Dr. Kuhadiya said.

The study was funded by Novo Nordisk. Dr. Kuhadiya had no relevant disclosures.

nmiller@frontlinemedcom.com

On Twitter @naseemmiller

LAS VEGAS – In patients with type 1 diabetes, adding a 1.8-mg daily dose of liraglutide to insulin significantly reduced hemoglobin A_1c, mean blood glucose, body weight, carbohydrate intake, and C-reactive protein, in a randomized study.

The 72-patient study also showed that adding liraglutide (Victoza) significantly improved quality of life and reduced systolic blood pressure in the groups that were receiving higher doses of the medicine.

Naseem Miller/Frontline Medical News

"Our findings have significant implications for the future treatment of type 1 diabetes," said Dr. Nitesh Kuhadiya of the State University of New York at Buffalo, who presented the findings at the annual meeting of the American Association of Clinical Endocrinologists. "Long term studies are needed to establish the durability of the effects."

In previous small, nonrandomized studies of patients with type 1 diabetes, liraglutide improved glycemic control and led to weight loss (Eur. J. Endocrinol. 2011;165:77-84; Endocr. Pract. 2013;19:963-7). They then decided to conduct a randomized controlled trial, which is the first of its kind, said Dr. Kuhadiya, who compared type 1 diabetes to a "wild horse that’s extremely difficult to tame and kicks you 10 times a day."

For the study, researchers randomized 72 patients to four groups to receive 0.6, 1.2, or 1.8 mg of liraglutide or a placebo daily for 12 weeks. One patient dropped out of placebo group, as well as five from the 1.2-mg and three from the 1.8-mg group.

The groups’ baseline characteristics were similar. All patients had type 1 diabetes for at least 1 year, were on insulin therapy, and had no detectable C-peptide in plasma. The mean age was 44 years, mean body weight was 83 kg, mean body mass index was 29 kg/m², mean HbA_1c was 7.5, and mean interval since diabetes diagnosis was 20 years. Nearly all (96%) patients were white and 56% were women.

There was a significant drop of nearly 10 mg/dL in average glucose in the 1.2- and 1.8-mg groups. The HbA_1c, also dropped in those two groups, although it was significant in only the 1.2-mg group, by about 0.8%. The drop was 0.4% in 1.8-mg group, 0.2% in the 0.6-mg group, and 0.3% in the placebo subjects.

There were also significant changes in the percent time spent in different glycemic thresholds for the 1.8-mg group. 

Patients on 1.2 mg and 1.8 mg of liraglutide spent about 3%-5% more time in the 70- to 160-mg/dL zone, respectively, although only those on 1.8 mg reached statistical significance. 

Again, the 1.2- and 1.8-mg groups spent less time in hyperglycemia, defined as 160-240 mg/dL, Dr. Kuhadiya said. No significant changes were observed in the other two groups. 

A similar trend was seen for severe hyperglycemia (250 mg/dL). 

There was, however, some additional hypoglycemia in the study in the range of 55 to 70 mg/dL, Dr. Kuhadiya reported. The 1.2- and 1.8-mg groups spent significantly more time (nearly 1%) in that range, but there was no incidence of hypoglycemia in the placebo and 0.6-mg groups. The results were similar for the less than 50 mg/dL range. However, there was no incidence of hypoglycemia requiring hospitalization or medical attention, Dr. Kuhadiya said. 

All three groups receiving liraglutide showed significant weight loss: nearly 5 kg in the 1.2- and 1.8-mg groups, and 3 kg in the 0.6-mg group, over a period of 12 weeks. 

The carbohydrate intake for the 1.2- and 1.8-mg groups also dropped significantly. 

Dr. Kuhadiya said that the findings also show that all changes are independent of each other. 

All groups showed a fall in C-reactive protein, which is a marker for cardiovascular risk, although only the 1.8-mg groups showed a statistical significance. "And this is important because most patients with type 1 diabetes have metabolic syndrome, and to be able to demonstrate all these changes and an additional fall in CRP means further protection from cardiovascular risk," Dr. Kuhadiya said.

The study was funded by Novo Nordisk. Dr. Kuhadiya had no relevant disclosures.

nmiller@frontlinemedcom.com

On Twitter @naseemmiller

LAS VEGAS – In patients with type 1 diabetes, adding a 1.8-mg daily dose of liraglutide to insulin significantly reduced hemoglobin A_1c, mean blood glucose, body weight, carbohydrate intake, and C-reactive protein, in a randomized study.

The 72-patient study also showed that adding liraglutide (Victoza) significantly improved quality of life and reduced systolic blood pressure in the groups that were receiving higher doses of the medicine.

Naseem Miller/Frontline Medical News

"Our findings have significant implications for the future treatment of type 1 diabetes," said Dr. Nitesh Kuhadiya of the State University of New York at Buffalo, who presented the findings at the annual meeting of the American Association of Clinical Endocrinologists. "Long term studies are needed to establish the durability of the effects."

In previous small, nonrandomized studies of patients with type 1 diabetes, liraglutide improved glycemic control and led to weight loss (Eur. J. Endocrinol. 2011;165:77-84; Endocr. Pract. 2013;19:963-7). They then decided to conduct a randomized controlled trial, which is the first of its kind, said Dr. Kuhadiya, who compared type 1 diabetes to a "wild horse that’s extremely difficult to tame and kicks you 10 times a day."

For the study, researchers randomized 72 patients to four groups to receive 0.6, 1.2, or 1.8 mg of liraglutide or a placebo daily for 12 weeks. One patient dropped out of placebo group, as well as five from the 1.2-mg and three from the 1.8-mg group.

The groups’ baseline characteristics were similar. All patients had type 1 diabetes for at least 1 year, were on insulin therapy, and had no detectable C-peptide in plasma. The mean age was 44 years, mean body weight was 83 kg, mean body mass index was 29 kg/m², mean HbA_1c was 7.5, and mean interval since diabetes diagnosis was 20 years. Nearly all (96%) patients were white and 56% were women.

There was a significant drop of nearly 10 mg/dL in average glucose in the 1.2- and 1.8-mg groups. The HbA_1c, also dropped in those two groups, although it was significant in only the 1.2-mg group, by about 0.8%. The drop was 0.4% in 1.8-mg group, 0.2% in the 0.6-mg group, and 0.3% in the placebo subjects.

There were also significant changes in the percent time spent in different glycemic thresholds for the 1.8-mg group. 

Patients on 1.2 mg and 1.8 mg of liraglutide spent about 3%-5% more time in the 70- to 160-mg/dL zone, respectively, although only those on 1.8 mg reached statistical significance. 

Again, the 1.2- and 1.8-mg groups spent less time in hyperglycemia, defined as 160-240 mg/dL, Dr. Kuhadiya said. No significant changes were observed in the other two groups. 

A similar trend was seen for severe hyperglycemia (250 mg/dL). 

There was, however, some additional hypoglycemia in the study in the range of 55 to 70 mg/dL, Dr. Kuhadiya reported. The 1.2- and 1.8-mg groups spent significantly more time (nearly 1%) in that range, but there was no incidence of hypoglycemia in the placebo and 0.6-mg groups. The results were similar for the less than 50 mg/dL range. However, there was no incidence of hypoglycemia requiring hospitalization or medical attention, Dr. Kuhadiya said. 

All three groups receiving liraglutide showed significant weight loss: nearly 5 kg in the 1.2- and 1.8-mg groups, and 3 kg in the 0.6-mg group, over a period of 12 weeks. 

The carbohydrate intake for the 1.2- and 1.8-mg groups also dropped significantly. 

Dr. Kuhadiya said that the findings also show that all changes are independent of each other. 

All groups showed a fall in C-reactive protein, which is a marker for cardiovascular risk, although only the 1.8-mg groups showed a statistical significance. "And this is important because most patients with type 1 diabetes have metabolic syndrome, and to be able to demonstrate all these changes and an additional fall in CRP means further protection from cardiovascular risk," Dr. Kuhadiya said.

The study was funded by Novo Nordisk. Dr. Kuhadiya had no relevant disclosures.

nmiller@frontlinemedcom.com

On Twitter @naseemmiller