Table 1 Summary of the included studies
Study ID | Title | Study design, country, and timing | Criteria | Sample size | MEDI0382 treatment regimen | Control group | study duration |
|---|---|---|---|---|---|---|---|
P. Ambery et al. (2018) [6] | MEDI0382, a GLP-1 and glucagon receptor dual agonist, in obese or overweight patients with type 2 diabetes: a randomized, controlled, double-blind, ascending dose and phase 2a study | RCT Germany, Dec 9, 2015, and Feb 24, 2017 | • Men or women aged 18–65 years with controlled T2DM • HbA1c levels of 6·5–8·5% at screening • BMI between 27 kg/m2 and 40 kg/m2 • Individuals who received metformin monotherapy of 500 mg or more within three months before screening or received an adjunct to metformin were eligible after a 4-week washout period | 113 patients (68 for MEDI0382, and 45 for placebo) | MEDI0382 100 mcg N = 6 MEDI0382 150 mcg N = 6 MEDI0382 200 mcg N = 7 MEDI0382 200 mcg N = 25 MEDI0382 300 mcg N = 12 MEDI0382 300 mcg N = 12 | N = 45 Participants received placebo matched to MEDI0382 dose | 3 years |
P. D. Ambery (2018) [15] | MEDI0382, a GLP-1/glucagon receptor dual agonist, meets safety and tolerability endpoints in a single-dose, healthy-subject, randomized, Phase 1 study | RCT Germany, 26 February 2015 and 12 August 2015, | • Healthy volunteers, male or female aged 18–45 years, are chosen approximately to a population of T2DM patients minimizing the chance for concomitant medical conditions • BMI between ≥ 22 kg.m–2 and ≤ 30 kg.m–2, • Bodyweight ≥ 70 kg • Individuals were required to have venous access suitable for multiple cannulations | 48 patients (36 for MEDI0382, and 12 for placebo) | MEDI0382 5 μg N = 6 MEDI0382 10 μg N = 6 MEDI0382 30 μg N = 6 MEDI0382 100 μg N = 6 MEDI0382 300 μg N = 6 MEDI0382 150 μg N = 6 | N = 12 Participants received placebo matched to MEDI0382 dose | 3 years |
Rajaa Nahra (2021) [16] | A Study to Evaluate the Efficacy and Safety of MEDI0382 in the Treatment of Overweight and Obese Subjects with Type 2 Diabetes | RCT, Bulgaria, Canada, Czechia, Germany, Mexico, Russian Federation, Slovakia, United States, 2 August 2017 and 14 June 2019 | • Male and female subjects aged ≥ 18 years with T2DM • BMI ≥ 25 kg/m2 • HbA1c range of 7.0% to 10.5% • Individuals Treated with metformin ≥ 1500 mg/day or more for at least two months before screening or using adjuvant medication for up to 2 weeks in the two months before screening is acceptable | 834 patients (612 for MEDI0382,110 for Liraglutide and 112 for placebo) | MEDI0382 100 mcg N = 100 MEDI0382 200 mcg N = 256 MEDI0382 300 mcg N = 256 | N = 112 Participants received placebo / Metformin tablets, total daily dose of ≥ 1500 mg (unless only tolerated at a lower dose) | 2 Years |
NCT03745937 | A Study to Evaluate the Safety and Tolerability of MEDI0382 in Overweight and Obese Subjects With Type 2 Diabetes Mellitus | RCT, Germany | • Participants aged 18 to 74 years with T2DM • BMI between 27 and 35 kg/m^2 • HbA1c range of 6.5% to 8.5% • Individuals Treated with metformin monotherapy where no significant dose change (increase or decrease >  = 500 mg/day) has occurred in the three months before screening | 20 patients (18 for MEDI0382 and 2 for placebo) | Participants received SC dose of MEDI0382 up-titrated weekly once daily up to 8 weeks during the up-titration period and thereafter once daily in 3-week TEP | N = 2 Participants received placebo matched to MEDI0382 dose | 4.5 months |
NCT03645421 | Safety and Tolerability Study of MEDI0382 in Japanese Pre-obese or Obese Subjects With Type 2 Diabetes | RCT, Japan | • Individuals diagnosed with T2DM • HbA1c range of 7.0% to 10.5% • Individuals with drug naïve at Visit 1 • BMI within the range of 24—40 kg/m2 | 61 patients (45 for MEDI0382 and 16 for placebo) | MEDI0382 100 mcg N = 15 MEDI0382 200 mcg N = 15 MEDI0382 300 mcg N = 15 | N = 16 Participants received placebo matched to MEDI0382 dose | 5 months |
NCT03596177 | A Study to Evaluate the Effect of MEDI0382 on Energy Balance in Overweight and Obese Subjects With Type 2 Diabetes Mellitus | RCT, United Kingdom | • Participants aged >  = 30 and <  = 75 years with T2DM • Body Mass Index > 28 and <  = 40 kg/m^2 • HbA1c <  = 8.0% • Individuals treated with metformin, with or without another adjuvant drug (increase or decrease > 50%) occurred three months before screening • For the participant on dual therapy, a 4-week washout of the non-metformin therapy will be performed before Visit | 28 patients (19for MEDI0382 and 9 for placebo) | MEDI0382 titrated up to 300 μg N = 19 | N = 9 Participants received placebo matched to MEDI0382 dose | 1 year and 1 month |
NCT03444584 | Study of MEDI0382 in Combination With Dapagliflozin and Metformin in Overweight/Obese Subject With Type 2 Diabetes | RCT, Germany, and Hungary | • Male and female participants aged >  = 18 years with T2DM • BMI between 25 kg/m^2 and 40 kg/m^2 • HA1c ranges between 7.0% and 10.0% • Individuals treated with metformin monotherapy (MTD > 1 g) at least eight weeks or treated with stable, oral doses of dapagliflozin 10 mg and metformin (MTD > 1 g) for at least three months before screening • For the participant on dual therapy in addition to metformin, 28 days washout period will be performed before the initial screening | 49 patients (25 for MEDI0382 and 24 for placebo) | MEDI0382 titrated up to 300 μg N = 25 | N = 24 Participants received placebo matched to MEDI0382 dose | 7 months |
Parker (2020) [17] | Efficacy, safety, and mechanistic insights of cotadutide a dual receptor glucagon-like peptide-1 and glucagon agonist | RCT, Germany | • Patients aged ≥ 18 years had T2DM taking metformin monotherapy, • HbA1c ranged from 6.5–8.5% • BMI of 27–40 kg/m2 • Individuals receiving metformin monotherapy were eligible if no significant dose changes (increase or decrease ≥ 500 mg/day) occurred in the three months before screening • Patients receiving adjuncts to metformin were allowed after a 4-week washout period | 65 patients (46 for MEDI0382 and 19 for placebo) | MEDI0382 titrated up to 300 μg N = 46 | N = 19 Participants received placebo matched to MEDI0382 dose | 6 months |
NCT03550378 | A Study to Look at the Effect MEDI0382 Has on Blood Sugar in People with Type 2 Diabetes and Kidney Problems and Also to Check That MEDI0382 is Well Tolerated | RCT, Germany, United Kingdom | • Patients aged ≥ 18 and < 85 years at the screening with T2DM managed with any insulin or oral therapy combination where no significant dose changes of oral therapy of more than 50% have occurred in the three months before screening • Body mass index (BMI) between 25 and 45 kg/m^2 • Haemoglobin A1c (HbA1c) range of 6.5% to 10.5% • eGFR ≥ 30 and < 60 mL/min/1.73 m^2 • Approximately 16 participants (40%) are required to have a screening eGFR ≥ 30 and < 45 mL/min/1.73 m^2, and at least 16 participants (40%) are required to have screening eGFR ≥ 45 and < 60 mL/min/1.73 m^2 | 41 patients (21 for MEDI0382 and 20 for placebo) | MEDI0382 titrated up to 300 μg N = 21 | N = 20 Participants received placebo matched to MEDI0382 dose | 7 months |