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)

Abstract

AimTo evaluate the pharmacodynamics of lixisenatide once daily vs sitagliptin once daily in Japanese patients with type 2 diabetes receiving insulin glargine U100.Materials and methodsThis 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.ResultsLixisenatide 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.ConclusionLixisenatide reduced PPG significantly more than sitagliptin, when these agents were added to basal insulin glargine U100, and was well tolerated.

Real World Effectiveness of Lixisenatide and Other Intensification Therapy in the Management of Type 2 Diabetic Patients Uncontrolled With Basal Insulin

“…Those responders have achieved the targeted HbA1c <7% with no symptomatic hypoglycemic episode after three months of intensification therapy and no weight gain. On the other hand,the numbers of hypoglycemic events reported with Lixisenatide were less than with the other intensification therapies in line with other clinical studies [25]. In addition, patients' body weight has significantly decreased after three months of Lixisenatide intensification therapy.…”

Comprehensive Evaluation of Combination Therapy with Basal Insulin and Either Lixisenatide or Vildagliptin in Japanese Patients with Type 2 Diabetes: A Randomized, Open-Label, Parallel-Group, Multicenter Study

“…Incretin-based drugs have been found to differ in efficacy with regard to limiting the postprandial increase in glucose concentration. Lixisenatide was thus shown to reduce postprandial glucose to a significantly greater extent compared with sitagliptin [ 18 , 19 ]. Vildagliptin also reduced both the mean amplitude of glycemic excursions and postprandial glucose to a significantly greater extent than sitagliptin [ 20 ].…”

Evolving Pharmacotherapeutic Strategies for Type 1 Diabetes Mellitus

“…48 Delayed gastric emptying is not seen in the dipeptidyl peptidase IV inhibitors, which would suggest less appetite suppression compared with GLP-1 agents. 49,50 Adult studies of sitagliptin in T1DM have shown some promise in reducing total daily insulin dose. 51,52 Both studies were limited in sample size and duration.…”