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

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/m(2), estimated glomerular filtration rate 30‐59 ml/min/1.73 m(2) 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

End-Stage Heart Failure with Multiple Intracardiac Thrombi: A Rescue Strategy

The use of ventricular assist devices as a bridge to transplantation has become a widely used option for patients with end-stage heart failure. In contrast to total artificial hearts, ventricular assist devices support the failing heart by bypassing one or both ventricles. In certain cases (myocardial tumors, graft failure, transplant rejection, endocarditis, intracardiac thrombus formation), however, it may be advantageous to excise the heart and replace it with an artificial device. Total artificial hearts are intracorporeal devices designed for this purpose. Unfortunately, some patients are too small or are, for other reasons, ineligible for a total artificial heart. We describe the case of a 55-year-old woman who had ischemic cardiomyopathy and thrombus formation in all 4 cardiac chambers. To reduce the risk of thromboembolic events, we elected to replace her heart completely with 2 extracorporeal ventricular assist devices. The heart was excised via a median sternotomy approach, and the outflow cannulae (from device to patient) were connected to both atrial remnants. The 2 inflow cannulae (from patient to device) were anastomosed end-to-end to the aorta and the pulmonary artery, respectively. After attaining a flow of more than 5 L, the 2 extracorporeal assist devices effectively and efficiently performed the work of the native heart. Thus re-established, organ perfusion was improved by this mechanically driven circulation, as signified by an initial decrease in creatinine and blood urea nitrogen levels. The patient, however, did not recover from postoperative neurological dysfunction and died of respiratory insufficiency and multiple-organ failure on the 26th postoperative day

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

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