QTERN™ is a fixed dose combination of saxagliptin and dapagliflozin and is indicated in adults aged 18 years and older with type 2 diabetes mellitus1
Glycaemic control of QTERN™ compared with its DPP-4 inhibitor and SGLT2 inhibitor monocomponents.5,10
- Sustained improvements in glycaemic control were seen at 52 weeks9
This was a multicenter, randomized, double-blind, placebo-controlled, parallel-group, phase 3 study. The study design consisted of a screening period and an open-label treatment period before randomization and a short-term (24 weeks), double-blind treatment period. Patients could then enter a longterm, 28 weeks extension, for a total of 52 weeks of triple-therapy treatment.
Patients with type 2 diabetes with glycated hemoglobin (HbA1c) 8.0-11.5% (64-102 mmol/mol) at screening and taking stable metformin immediate release (IR) or extended release (XR) (≥ 1,500 mg/day) for ≥ 8 weeks before screening were included. At the end of the screening period, patients were switched to 16 weeks of open-label treatment with the nearest multiple of metformin IR 500 mg and dapagliflozin (10 mg/day). For inclusion into the randomized, 24-week, double-blind treatment period, patients had to have an HbA1c 7.0-10.5% (53-91 mmol/mol) at week 2 of the open-label treatment period. Following the open-label period, eligible patients were randomized 1:1 using a centralized blocked randomization schedule and received placebo or saxagliptin 5 mg/day in addition to open-label dapagliflozin 10 mg/day and metformin IR for 24 weeks. Patients completing the double-blind period could enter the 28-week long-term extension.
The primary end point was the mean change from baseline in HbA1c after 24 weeks of double-blind treatment with a saxagliptin versus a placebo add-on to dapagliflozin plus metformin. Secondary end points were mean change from baseline at 24 weeks in 2-hour postprandial glucose (PPG) following a liquid meal tolerance test (MTT), mean change from baseline at 24 weeks in FPG, and the proportion of patients achieving a therapeutic glycemic response, defined as HbA1c <7.0% (53 mmol/mol), at 24 weeks. Other end points included the proportion of patients rescued or discontinued from the study for lack of efficacy, change from baseline in PPG area under the concentration-time curve from time 0 to 180 min change in serum lipids from baseline, and change in body weight from baseline.
- Maintains the secondary benefit of weight loss10*
*QTERNTM is not indicated for the management of weight loss or high blood pressure. Weight change was a secondary endpoint in clinical trials.1
This was a multicenter, randomized, double-blind, placebo-controlled, parallel-group, phase 3 study. The study design consisted of a screening and open-label treatment period followed by a randomized, 24-week, short-term, double-blind treatment period; this was followed with a long-term extension of an additional 28 weeks for a total of 52 weeks of triple therapy.
Two groups of patients (>18 years of age) with type 2 diabetes and inadequate glycemic control were included in the open-label treatment period based on DPP-4 inhibitor use. Patients in stratum A had a glycated haemoglobin (HbA1c) level of 8.0-11.5% (64-102 mmol/mol at screening and were receiving stable metformin therapy (immediate release [IR] or extended release [XR] >1,500 mg/day) for at least 8 weeks before screening. These patients were switched to the nearest lower or higher multiple of metformin IR 500-mg tablets and saxagliptin 5 mg/day for 16 weeks of open-label treatment. Patients in stratum B had an HbA1c level of 7.5-10.5% (58-91 mmol/mol) and were receiving stable metformin (IR or XR >1,500 mg/day) and a DPP-4 inhibitor at the maximum approved cose for at least 8 weeks before the screening visit. These patients were switched to the nearest lower or higher multiple of metformin IR 500-mg tablets, and any DPP-4 inhibitor was replaced by saxagliptin 5 mg/day. They received 8 weeks of open-label treatment with this regimen.
The primary endpoint was the mean change from baseline in HbA1c level after 24 weeks of double-blind treatment with dapagliflozin versus placebo add-on to saxagliptin plus metformin. Secondary endpoints were the mean change from baseline at 24 weeks in FPG level, 2-h postprandial glucose (PPG) level following a liquid meal tolerance test (MTT), body weight and the mean proportion of patients achieving a therapeutic glycemic response, defined as an HbA1c level of <7.0% (53 mmol/mol), after 24 weeks. The composition of the liquid MTT was dependent on the investigational site and consisted of 360-375 kcal, 14.0-28.2 g of protein, 10.5-14.0 g of fat, and 42-45 g of carbohydrates; 16.8-22.0 g of sugars as a component of carbohydrates. Other endpoints included the proportion of patients rescued or discontinued from the study for lack of efficacy, the change from baseline in the PPG area under the concentration-time curve from 0 to 180 min (AUCO-180 min) during a liquid MTT, and the change from baseline in serum lipid levels.