Chromatographic study of sitagliptin and ertugliflozin under quality-by-design paradigm

Abstract The present study entails the systematic development and validation of a stability-indicating RP-HPLC method for the analysis of sitagliptin and ertugliflozin in a fixed-dose combination. Analytical quality by design (AQbD) concepts were used to define critical method variables, employing Pareto risk assessment and a Placket-Burman screening design, preceded by a Box-Behnken design with response surface analysis to optimise critical method parameters such as % acetonitrile (X1), buffer pH (X2) and column oven temperature (X3). Multiple response optimisation (Derringer's desirability) of variables was accomplished by studying critical analytical attributes, such as resolution, retention time and theoretical plates. The title analytes were separated effectively on a PRONTOSIL C18 column at 37 °C using a mobile phase of acetonitrile:acetate buffer, pH 4.4 (36:64 percent v/v), pumped at a flow rate of 1 mL/min, and UV detection at 225 nm. Linearity was observed over a concentration range of 25-150 µg/mL and 3.75-22.5 µg/mL at retention times of 2.82 and 3.92 min for sitagliptin and ertugliflozin, respectively. The method obeyed all validation parameters of the ICH Q2(R1) guidelines. The proposed robust method allows the study of the selected drugs in pharmaceutical dosage forms as well as in drug stability studies under various stress conditions.

A network meta-analysis of efficacy and safety of multiple-dose of ertugliflozin in patients with type 2 diabetes / 西安交通大学学报(医学版)

Objective: To evaluate the efficacy and safety of mutiple-dose of ertugliflozin in the treatment of type 2 diabetes mellitus (T2DM) with network meta-analysis. Methods: The databases of Cochrane Library, Embase, PubMed, OVID, Web of Science, CNKI, VIP and Wanfang were retrieved with the computer. The reviewers assessed the quality of the literature according to the Cochrane Handbook, and made the analysis using Review Manager 5.3, R software and Stata 14.0 software. Results: Four randomized controlled trials (RCTs) involving 1 433 patients were included. The results of network meta-analysis showed that ertugliflozin of 5 mg, 10 mg, 15 mg and 25 mg significantly reduced HbA1c when compared with placebo; ertugliflozin of 15 mg ranked the first in the rank probability diagram. In the respect of FPG, ertugliflozin of 5 mg, 10 mg, 15 mg and 25 mg significantly reduced FPG when compared with placebo, and ertugliflozin of 10 mg ranked the first in the rank probability diagram. Ertugliflozin of 5 mg, 10 mg, 15 mg and 25 mg significantly reduced body weight when compared with placebo, and ertugliflozin of 10 mg ranked the first in the rank probability diagram. Ertugliflozin of 10 mg and 15 mg groups had the lowest incidence of total adverse reactions and incidence of hypoglycemia, while the incidence in ertugliflozin of 5mg and 10 mg groups was the lowest in patients due to the withdrawal rate of adverse reactions. Conclusion: The different dosage groups of ertugliflozin had average efficacy and safety in treating with T2DM. However, due to the small sample size of the studies included, it is necessary to develop larger samples and high-quality literature for more comprehensive verification.

Safety of ertugliflozin as a monotherapy for the treatment of type diabetes: a meta-analysis / 中国药学杂志

OBJECTIVE: To systematically evaluate the safety of ertugliflozin as a monotherapy for the treatment of type Ⅱ diabetes. METHODS: The randomized controlled trials(RCTs) of ertugliflozin for type Ⅱ diabetes were searched in the clinical trial registries and the related databases, such as CNKI, WANFANG, The Cochrane Library, Embase and Clinical Trials. The literatures were screened according to inclusion and exclusion criterias.After the data extraction and assessing the quality of included studies with Cochrane Handbook 5.3.3, Meta-analysis was conducted with RevMan5.3 software and the sensitivity of outcomes were analyzed by the Stata14.0. RESULTS: The six individual randomized controlled trials were eligible. The 4 078 patients were enrolled. There are some results of Meta-analysis. At 26 weeks, compared to the control subjects, the risk of genital mycotic infection(GMI) in ertugliflozin group was higher(RR=6.25, 95%CI: 2.98-6.61, P30% in eGFR were no significant difference. There were no significant difference between 5 and 15 mg group on the safety indicators at 52 weeks. CONCLUSION: Ertugliflozin could cause GMI regularly. And the risk of female patients with GMI was higher than male. Meanwhile, it was easy to reduce eGFR, but most of them were reversible.Ertugliflozin was safe in urinary tract infection, symptomatic hypoglycaemia and hypovolaemia. However, there is no obvious difference in the safety of different dosage groups.

Ertugliflozin: a novel anti-diabetic drug

Diabetes Mellitus is a disorder of global proportion. Despite various treatment modalities presently being available, yet the desired glycaemic control and patient outcomes have not been achieved completely. Sodium glucose co-transporter type 2 inhibitors (SGLT2 inhibitors) are one such promising group of emerging drugs in diabetes treatment. Ertugliflozin prevents the reabsorption of glucose by inhibiting sodium-glucose cotransporter-2 (SGLT2) at proximal convoluted tubules. Ertugliflozin is available as 5mg and 15mg tablets. Ertugliflozin has been related to genital mycotic infections and urinary tract infections. Benefits of Ertugliflozin include better control on blood glucose, body weight and blood pressure.