Efficacy and safety of cotadutide, a dual glucagon-like peptide-1 and glucagon receptor agonist, in a randomized phase 2a study of patients with type 2 diabetes and chronic kidney disease

TY - JOUR

T1 - Efficacy and safety of cotadutide, a dual glucagon-like peptide-1 and glucagon receptor agonist, in a randomized phase 2a study of patients with type 2 diabetes and chronic kidney disease

AU - Parker, Victoria E. R.

AU - Hoang, Thuong

AU - Schlichthaar, Heike

AU - Gibb, Fraser W.

AU - Wenzel, Barbara

AU - Posch, Maximillian G.

AU - Rose, Ludger

AU - Chang, Yi Ting

AU - Petrone, Marcella

AU - Hansen, Lars

AU - Ambery, Philip

AU - Jermutus, Lutz

AU - Heerspink, Hiddo J. L.

AU - McCrimmon, Rory J.

N1 - Funding Information: This study (NCT03550378) was sponsored by AstraZeneca. Publisher Copyright: © 2022 AstraZeneca. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

PY - 2022/7

Y1 - 2022/7

N2 - Aim: To assess the efficacy, safety and tolerability of cotadutide in patients with type 2 diabetes mellitus and chronic kidney disease.Materials and Methods: In this phase 2a study (NCT03550378), patients with body mass index 25-45 kg/m2, estimated glomerular filtration rate 30-59 ml/min/1.73 m2 and type 2 diabetes [glycated haemoglobin 6.5-10.5% (48-91 mmol/mol)] controlled with insulin and/or oral therapy combination, were randomized 1:1 to once-daily subcutaneous cotadutide (50-300 μg) or placebo for 32 days. The primary endpoint was plasma glucose concentration assessed using a mixed-meal tolerance test.Results: Participants receiving cotadutide (n = 21) had significant reductions in the mixed-meal tolerance test area under the glucose concentration-time curve (–26.71% vs. +3.68%, p <.001), more time in target glucose range on continuous glucose monitoring (+14.79% vs. –21.23%, p =.001) and significant reductions in absolute bodyweight (–3.41 kg vs. –0.13 kg, p <.001) versus placebo (n = 20). In patients with baseline micro- or macroalbuminuria (n = 18), urinary albumin-to-creatinine ratios decreased by 51% at day 32 with cotadutide versus placebo (p =.0504). No statistically significant difference was observed in mean change in estimated glomerular filtration rate between treatments. Mild/moderate adverse events occurred in 71.4% of participants receiving cotadutide and 35.0% receiving placebo.Conclusions: We established the efficacy of cotadutide in this patient population, with significantly improved postprandial glucose control and reduced bodyweight versus placebo. Reductions in urinary albumin-to-creatinine ratios suggest potential benefits of cotadutide on kidney function, supporting further evaluation in larger, longer-term clinical trials.

AB - Aim: To assess the efficacy, safety and tolerability of cotadutide in patients with type 2 diabetes mellitus and chronic kidney disease.Materials and Methods: In this phase 2a study (NCT03550378), patients with body mass index 25-45 kg/m2, estimated glomerular filtration rate 30-59 ml/min/1.73 m2 and type 2 diabetes [glycated haemoglobin 6.5-10.5% (48-91 mmol/mol)] controlled with insulin and/or oral therapy combination, were randomized 1:1 to once-daily subcutaneous cotadutide (50-300 μg) or placebo for 32 days. The primary endpoint was plasma glucose concentration assessed using a mixed-meal tolerance test.Results: Participants receiving cotadutide (n = 21) had significant reductions in the mixed-meal tolerance test area under the glucose concentration-time curve (–26.71% vs. +3.68%, p <.001), more time in target glucose range on continuous glucose monitoring (+14.79% vs. –21.23%, p =.001) and significant reductions in absolute bodyweight (–3.41 kg vs. –0.13 kg, p <.001) versus placebo (n = 20). In patients with baseline micro- or macroalbuminuria (n = 18), urinary albumin-to-creatinine ratios decreased by 51% at day 32 with cotadutide versus placebo (p =.0504). No statistically significant difference was observed in mean change in estimated glomerular filtration rate between treatments. Mild/moderate adverse events occurred in 71.4% of participants receiving cotadutide and 35.0% receiving placebo.Conclusions: We established the efficacy of cotadutide in this patient population, with significantly improved postprandial glucose control and reduced bodyweight versus placebo. Reductions in urinary albumin-to-creatinine ratios suggest potential benefits of cotadutide on kidney function, supporting further evaluation in larger, longer-term clinical trials.

UR - https://www.scopus.com/pages/publications/85128760827

U2 - 10.1111/dom.14712

DO - 10.1111/dom.14712

M3 - Article

C2 - 35403793

AN - SCOPUS:85128760827

SN - 1462-8902

VL - 24

SP - 1360

EP - 1369

JO - Diabetes, Obesity and Metabolism

JF - Diabetes, Obesity and Metabolism

IS - 7

ER -