BOSTON – Switching from sitagliptin to liraglutide, in combination with metformin, improved control of hypoglycemia and resulted in greater weight loss in patients with type 2 diabetes, reported Dr. Maximo Maislos at the annual meeting of the Endocrine Society.
Results of a randomized, double-blind, double-dummy, active-controlled 26-week trial have indicated that liraglutide can be used as an add-on to metformin for patients with type 2 diabetes who have remained hyperglycemic.
Dr. Maximo Maislos
“Switching from sitagliptin to liraglutide resulted in superior [glycated hemoglobin] and body weight reductions, compared with continued sitagliptin treatment,” said Dr. Maximo Maislos of Ben-Gurion University, Beer-Sheva, Israel.
The LIRA-SWITCH trial (Efficacy and Safety of Switching From Sitagliptin to Liraglutide in Subjects With Type 2 Diabetes Not Achieving Adequate Glycaemic Control on Sitagliptin and Metformin) involved 407 patients. The majority (60%) were male; mean age was 56 years and mean body mass index was 32 kg/m2. The subjects had all been treated with sitagliptin (100 mg/day) and metformin (greater than or equal to 1,500 mg/day or a maximum tolerated dose greater than or equal to 1,000 mg/day) for at least 90 days. Hyperglycemia had not been well controlled, with a mean hemoglobin A1C (HbAIC) level of 8.3% (67 mmol/mol). The mean duration of type 2 diabetes was 8 years.
Subjects were randomized to continued sitagliptin along with metformin (n = 204) or liraglutide (1.8 mg daily) along with metformin (n = 203).
After 26 weeks of treatment, reduction in HbAIC was significantly greater in the liraglutide arm than in the sitagliptin arm (1.14% vs. 0.54%; estimated treatment difference [ETD], –0.61%; 95% confidence interval, –0.82 to –0.40; P less than .0001). Those receiving liraglutide had statistically significantly greater weight loss, compared with those who continued on sitagliptin.
The less than 7% and less than or equal to 6.5% target levels of HbAIC were achieved by 50.6% and 29.5%, respectively, of patients in the liraglutide arm. These percentages were significantly higher than the respective 26.9% and 9.9% of patients in the sitagliptin arm (P less than .0001 for both). Fasting plasma glucose levels were significantly reduced with liraglutide treatment while decreases in systolic and diastolic blood pressure were similar in the two study arms.
Adverse events (AEs) occurred more often in the liraglutide group than in the sitagliptin group (68.8% vs. 56.9%). Thirteen patients receiving liraglutide discontinued treatment, compared with five in the sitagliptin arm. The most common AEs in the liraglutide group were gastrointestinal disorders, principally nausea (21.8% with liraglutide vs. 7.8% with sitagliptin) and diarrhea (16.3% with liraglutide vs. 9.3% with sitagliptin), followed by decreased appetite (8.9% vs. 3.4%, respectively). These AEs tended to subside within the first few weeks of treatment.
Serious AEs occurred in eight patients in both arms. Rescue medication was needed for 30 patients receiving sitagliptin and 11 patients receiving liraglutide. No cases of pancreatitis were reported. In the sitagliptin group, one subject each developed bladder cancer and squamous cell carcinoma. Nocturnal hypoglycemia did not develop in either trial arm.
Funding was provided by liraglutide maker Novo Nordisk. Dr. Maislos had no disclosures.