EASD: Gliptin Tx Works Long-Term for Glycemic Control
By Ed Susman, Contributing Writer, September 19, 2011
Action Points
Note that these studies were published as abstracts and were presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.
Explain that long-term treatment of type 2 diabetes with dipeptidyl peptidase-4 (DPP-4) inhibitors for two years appeared to maintain improvement in glycosylated hemoglobin A1c levels.
Note that the reduction in HbA1c was observed for add-on therapy with metformin and for metformin plus sulfonylurea.
Review
LISBON -- Long-term treatment of type 2 diabetes with dipeptidyl peptidase-4 (DPP-4) inhibitors for two years appeared to maintain improvement in glycosylated hemoglobin A1c levels, researchers reported here.
In one study, treatment with linagliptin (Tradjenta) at the end of a 24-week randomized clinical trial resulted in a mean 0.8% decline in HbA1c after 102 weeks of treatment. In addition, patients still had a 0.8% decline in HbA1c, reported David Owens MD, at the European Association for the Study of Diabetes. Owens is from the Center for Endocrinology and Diabetes Science at Cardiff University in the U.K.
In a second study, Douglas Fleming, MD, an investigator for Bristol-Myers Squibb in Princeton, N.J., said treatment with its DPP-4 inhibitor saxagliptin (Onglyza) showed a similar pattern after 52 weeks of therapy: Patients taking saxagliptin (5 mg) in addition to insulin were able to achieve a 0.37% net decline in HbA1c, regardless of whether the patients were also taking metformin.
"The results seen in these extension studies is what we would have expected to see in treating type 2 diabetes patients over the long term," commented Carolyn Deacon, PhD, senior lecturer at the Panum Institute, University of Copenhagen. Deacon moderated the session during which Owens and Fleming presented their findings.
Linagliptin: Long-Term Glycemic Control
Owens said that in his study, patients were randomized to receive linagliptin or placebo for 24 weeks in four controlled clinical trials aimed at determining the efficacy of linagliptin.
In the open-label extension study, patients initially treated with linagliptin were continued on the drug for an additional 78 weeks. Patients initially started on placebo were switched to linagliptin (5 mg) for 78 weeks. The total follow-up time was two years.
For the pooled results, 1,532 patients were included in the 102-week linagliptin study and 589 patients in the 78-week group. The patients were about 57 years of age and about 52% were men. About 57% of the total group was white; about 42% was Asian.
By the end of 102 weeks, the HbA1c had not changed, which Owens noted met the coefficient of durability of 0.14%, meaning there was no relevant increase in HbA1c from week 24 to week 102 (P<0.0001).
He demonstrated that the maintenance of HbA1c levels was similar for the following:
Patients on linagliptin monotherapy achieved a mean 0.5% decrease from a baseline value of 7.98%.
Patients who had linagliptin added onto metformin achieved a mean 0.74% reduction in HbA1c from a baseline value of 8.06%.
Patients with linagliptin added on to treatment with metformin and a sulfonylurea achieved a mean 0.7% reduction in HbA1c from a baseline value of 8.13%.
Patients with an initial combination with pioglitazone (Actos) achieved a 1.5% reduction in HbA1c from baseline levels of 8.55%.
"Linagliptin provides sustained long-term glycemic control when used as monotherapy or add-on to other glucose-lowering agents over two years," Owens said.
In addition, he said that linagliptin was well tolerated by patients during the study and that there was no clinically relevant increase in hypoglycemia or weight gain.
Sustained Results With Saxagliptin Add-On
The story was similar for patients in the saxagliptin study, Fleming illustrated in his oral presentation.
The researchers tested oral saxagliptin for 24 weeks to assess the short-term efficacy and safety of the molecule and then tested its long-term efficacy for 28 weeks. The 24-week trial results were presented at the American Diabetes Association meeting in June.
The enrollees were about 57-years-old; about 57% were women. More than three-fourths were white. The mean duration of type 2 diabetes was 12 years. The baseline HbA1c at the start of the trial was about 8.7%.
In the 52-week analysis, patients achieved a 0.75% decrease from baseline in HbA1c if they were taking saxagliptin (5 mg) added to insulin. That compared with a 0.38% reduction among the patients taking placebo (P<0.0001).
Initially, 304 patients started the study on saxagliptin and 151 patients were enrolled on placebo. About 18% of patients dropped out of the trial, so that 246 patients finished the trial on saxagliptin and 125 finished the trial on placebo.
Fleming also noted a greater increase from baseline mean daily insulin dose in patients who received placebo compared with patients who received saxagliptin.
The proportion of patients in each treatment group who experienced at least one adverse event over the 52-week treatment period was similar. The most common events included hypoglycemia, urinary tract infection, nasopharyngitis, upper respiratory tract infection, headache, and bronchitis.
During the initial 24-week period, patients were advised to maintain stable insulin doses, which could be decreased to reduce the risk of hypoglycemia. Patients with hyperglycemia or with substantially increased insulin had a rescue visit and remained in the study on a flexible insulin regimen.
During the extension period, all patients were able to adopt a flexible insulin regimen. Sixty-nine percent of patients were treated with metformin, and the dose could not be changed during the study.
Fleming reported that 21.3% of patients on saxagliptin achieved a therapeutic glycemic response of HbA1c less than 7%, while 8.7% of patients on placebo achieved that goal.
Mean body weight increase 0.8 kg on saxagliptin and 0.5 kg on placebo. The difference was not statistically significant, Fleming reported.
"Saxagliptin was well tolerated when added to insulin with or without concomitant metformin," Fleming said. "Consistent efficacy results were observed regardless of metformin use."