5 research outputs found
Environmental impact evaluation of decentralized sewage treatment technologies: A life cycle assessment approach
Forecasting mortality rates using hybrid Lee鈥揅arter model, artificial neural network and random forest
Efficacy and safety of a fixed-ratio combination of insulin degludec and liraglutide (IDegLira) compared with its components given alone: Results of a phase 3, open-label, randomised, 26-week, treat-to-target trial in insulin-naive patients with type 2 diabetes
BACKGROUND:
A fixed-ratio combination of the basal insulin analogue insulin degludec and the glucagon-like peptide-1 (GLP-1) analogue liraglutide has been developed as a once-daily injection for the treatment of type 2 diabetes. We aimed to compare combined insulin degludec-liraglutide (IDegLira) with its components given alone in insulin-naive patients.
METHODS:
In this phase 3, 26-week, open-label, randomised trial, adults with type 2 diabetes, HbA1c of 7-10% (inclusive), a BMI of 40 kg/m(2) or less, and treated with metformin with or without pioglitazone were randomly assigned (2:1:1) to daily injections of IDegLira, insulin degludec, or liraglutide (1\ub78 mg per day). IDegLira and insulin degludec were titrated to achieve a self-measured prebreakfast plasma glucose concentration of 4-5 mmol/L. The primary endpoint was change in HbA1c after 26 weeks of treatment, and the main objective was to assess the non-inferiority of IDegLira to insulin degludec (with an upper 95% CI margin of 0\ub73%), and the superiority of IDegLira to liraglutide (with a lower 95% CI margin of 0%). This study is registered with ClinicalTrials.gov, number NCT01336023.
FINDINGS:
1663 adults (mean age 55 years [SD 10], HbA1c 8\ub73% [0\ub79], and BMI 31\ub72 kg/m(2) [4\ub78]) were randomly assigned, 834 to IDegLira, 414 to insulin degludec, and 415 to liraglutide. After 26 weeks, mean HbA1c had decreased by 1\ub79% (SD 1\ub71) to 6\ub74% (1\ub70) with IDegLira, by 1\ub74% (1\ub70) to 6\ub79% (1\ub71) with insulin degludec, and by 1\ub73% (1\ub71) to 7\ub70% (1\ub72) with liraglutide. IDegLira was non-inferior to insulin degludec (estimated treatment difference -0\ub747%, 95% CI -0\ub758 to -0\ub736, p<0\ub70001) and superior to liraglutide (-0\ub764%, -0\ub775 to -0\ub753, p<0\ub70001). IDegLira was generally well tolerated; fewer participants in the IDegLira group than in the liraglutide group reported gastrointestinal adverse events (nausea 8\ub78 vs 19\ub77%), although the insulin degludec group had the fewest participants with gastrointestinal adverse events (nausea 3\ub76%). We noted no clinically relevant differences between treatments with respect to standard safety assessments, and the safety profile of IDegLira reflected those of its component parts. The number of confirmed hypoglycaemic events per patient year was 1\ub78 for IDegLira, 0\ub72 for liraglutide, and 2\ub76 for insulin degludec. Serious adverse events occurred in 19 (2%) of 825 patients in the IDegLira group, eight (2%) of 412 in the insulin degludec group, and 14 (3%) of 412 in the liraglutide group.
INTERPRETATION:
IDegLira combines the clinical advantages of basal insulin and GLP-1 receptor agonist treatment, resulting in improved glycaemic control compared with its components given alone
Efficacy and safety of a fixed-ratio combination of insulin degludec and liraglutide (IDegLira) compared with its components given alone: results of a phase 3, open-label, randomised, 26-week, treat-to-target trial in insulin-naive patients with type 2 diabetes.
BACKGROUND:
A fixed-ratio combination of the basal insulin analogue insulin degludec and the glucagon-like peptide-1 (GLP-1) analogue liraglutide has been developed as a once-daily injection for the treatment of type 2 diabetes. We aimed to compare combined insulin degludec-liraglutide (IDegLira) with its components given alone in insulin-naive patients.
METHODS:
In this phase 3, 26-week, open-label, randomised trial, adults with type 2 diabetes, HbA1c of 7-10% (inclusive), a BMI of 40 kg/m(2) or less, and treated with metformin with or without pioglitazone were randomly assigned (2:1:1) to daily injections of IDegLira, insulin degludec, or liraglutide (1路8 mg per day). IDegLira and insulin degludec were titrated to achieve a self-measured prebreakfast plasma glucose concentration of 4-5 mmol/L. The primary endpoint was change in HbA1c after 26 weeks of treatment, and the main objective was to assess the non-inferiority of IDegLira to insulin degludec (with an upper 95% CI margin of 0路3%), and the superiority of IDegLira to liraglutide (with a lower 95% CI margin of 0%). This study is registered with ClinicalTrials.gov, number NCT01336023.
FINDINGS:
1663 adults (mean age 55 years [SD 10], HbA1c 8路3% [0路9], and BMI 31路2 kg/m(2) [4路8]) were randomly assigned, 834 to IDegLira, 414 to insulin degludec, and 415 to liraglutide. After 26 weeks, mean HbA1c had decreased by 1路9% (SD 1路1) to 6路4% (1路0) with IDegLira, by 1路4% (1路0) to 6路9% (1路1) with insulin degludec, and by 1路3% (1路1) to 7路0% (1路2) with liraglutide. IDegLira was non-inferior to insulin degludec (estimated treatment difference -0路47%, 95% CI -0路58 to -0路36, p<0路0001) and superior to liraglutide (-0路64%, -0路75 to -0路53, p<0路0001). IDegLira was generally well tolerated; fewer participants in the IDegLira group than in the liraglutide group reported gastrointestinal adverse events (nausea 8路8 vs 19路7%), although the insulin degludec group had the fewest participants with gastrointestinal adverse events (nausea 3路6%). We noted no clinically relevant differences between treatments with respect to standard safety assessments, and the safety profile of IDegLira reflected those of its component parts. The number of confirmed hypoglycaemic events per patient year was 1路8 for IDegLira, 0路2 for liraglutide, and 2路6 for insulin degludec. Serious adverse events occurred in 19 (2%) of 825 patients in the IDegLira group, eight (2%) of 412 in the insulin degludec group, and 14 (3%) of 412 in the liraglutide group.
INTERPRETATION:
IDegLira combines the clinical advantages of basal insulin and GLP-1 receptor agonist treatment, resulting in improved glycaemic control compared with its components given alone