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To evaluate whether the addition of sotagliflozin to optimized insulin significantly increases the proportion of adults with type 1 diabetes who achieve HbA1c goals without weight gain.In a patient-level pooled analysis (n = 1575) of data from two phase 3, 52-week clinical trials (inTandem1 and inTandem2), the change from baseline in HbA1c and weight as well as the proportion of participants achieving an HbA1c of less than 7% without weight gain were compared between groups treated with placebo, sotagliflozin 200 mg and sotagliflozin 400 mg.From a mean baseline HbA1c of 7.7%, mean HbA1c changes at week 24 were -0.36% (95% CI -0.44% to -0.29%) and -0.38% (-0.45% to -0.31%) with sotagliflozin 200 and 400 mg versus placebo (P = .001 for both), respectively, with sustained effects through week 52. Weight significantly decreased at weeks 24 and 52 in both sotagliflozin groups compared with placebo. At week 52, the proportion of patients who achieved an HbA1c of less than 7% without weight gain was 21.8% with sotagliflozin 200 mg, 26.1% with sotagliflozin 400 mg and 9.1% with placebo (P .001). Other HbA1c, weight and safety composite variables showed similar significant trends.When added to optimized insulin therapy, sotagliflozin improved glycaemic control and body weight and enabled more adults with type 1 diabetes to achieve HbA1c goals without weight gain over 52 weeks, although there was more diabetic ketoacidosis relative to placebo.

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.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 (1·8 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 0·3%), and the superiority of IDegLira to liraglutide (with a lower 95% CI margin of 0%). This study is registered with ClinicalTrials.gov, number NCT01336023.1663 adults (mean age 55 years [SD 10], HbA1c 8·3% [0·9], and BMI 31·2 kg/m(2) [4·8]) were randomly assigned, 834 to IDegLira, 414 to insulin degludec, and 415 to liraglutide. After 26 weeks, mean HbA1c had decreased by 1·9% (SD 1·1) to 6·4% (1·0) with IDegLira, by 1·4% (1·0) to 6·9% (1·1) with insulin degludec, and by 1·3% (1·1) to 7·0% (1·2) with liraglutide. IDegLira was non-inferior to insulin degludec (estimated treatment difference -0·47%, 95% CI -0·58 to -0·36, p0·0001) and superior to liraglutide (-0·64%, -0·75 to -0·53, p0·0001). IDegLira was generally well tolerated; fewer participants in the IDegLira group than in the liraglutide group reported gastrointestinal adverse events (nausea 8·8 vs 19·7%), although the insulin degludec group had the fewest participants with gastrointestinal adverse events (nausea 3·6%). 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 1·8 for IDegLira, 0·2 for liraglutide, and 2·6 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.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.Novo Nordisk.