Reduction of postprandial glucose by lixisenatide vs sitagliptin treatment in Japanese patients with type 2 diabetes on background insulin glargine: A randomized phase IV study (NEXTAGE Study).

AIM: To evaluate the pharmacodynamics of lixisenatide once daily vs sitagliptin once daily in Japanese patients with type 2 diabetes receiving insulin glargine U100.

MATERIALS AND METHODS: This multicentre, open-label, phase IV study (NEXTAGE Study; ClinicalTrials.gov number, NCT02200991) randomly assigned 136 patients to either lixisenatide once daily via subcutaneous injection (10 µg initially increased weekly by 5 up to 20 µg) or once-daily oral sitagliptin 50 mg. The primary endpoint was the change in postprandial glucose (PPG) exposure 4 hours after a standardized breakfast (PPG area under the plasma glucose concentration-time curve [AUC0:00-4:00h ]) from baseline to day 29.

RESULTS: Lixisenatide reduced PPG exposure to a statistically significantly greater extent than sitagliptin: least squares (LS) mean change from baseline in PPG AUC0:00-4:00h was -347.3 h·mg/dL (-19.3 h·mmol/L) in the lixisenatide group and -113.3 h·mg/dL (-6.3 h·mmol/L) in the sitagliptin group (LS mean between-group difference -234.0 h·mg/dL [-13.0 h·mmol/L], 95% confidence interval -285.02 to -183.00 h·mg/dL [-15.8 to -10.2 h·mmol/L]; P < .0001). Lixisenatide led to significantly greater LS mean reductions in maximum PPG excursion than sitagliptin (-122.4 vs -46.6 mg/dL [-6.8 vs -2.6 h·mmol/L]; P < .0001). Change-from-baseline reductions in exposure to C-peptide, fasting glycoalbumin levels, and the gastric emptying rate were greater in the lixisenatide than in the sitagliptin group. The incidence of treatment-emergent adverse events was higher with lixisenatide (60.9%) than with sitagliptin (16.4%), with no serious events or severe hypoglycaemia reported.

CONCLUSION: Lixisenatide reduced PPG significantly more than sitagliptin, when these agents were added to basal insulin glargine U100, and was well tolerated.