- Once-daily cotadutide, an investigational dual receptor agonist with glucagon-like peptide-1 (GLP-1) and glucagon receptor activity, was associated with a reduction in hepatic glycogen in obese and overweight patients with type 2 diabetes (T2D).
Why this matters
- Pharmacological strategies are needed to help reduce excess glycogen in patients with T2D.
- Patients with T2D and a BMI of ≥27 to ≤40 kg/m2 were randomly assigned:
- Once-daily subcutaneous cotadutide (n=12) uptitrated weekly from 100 to 300 µg;
- Placebo (n=9).
- Hepatic glycogen concentrations were measured at baseline and 4, 9, 14, and 24 hours after a mixed-meal tolerance test (MMTT).
- Change in hepatic glycogen from baseline to 4 hours after the MMTT comprised the primary endpoint.
- Funding: AstraZeneca.
- A greater reduction in hepatic glycogen was observed with cotadutide vs placebo at 4 hours (−100.2 [90% CI, −150.2 to −50.1] mmol/L vs +5.5 [90% CI, −47.2 to 58.3] mmol/L; P=.023).
- Cotadutide was associated with a significantly greater overall change in glycogen area under the curve (AUC) of 24 hours (−27.3% vs +1.78%; P=.003).
- Compared with placebo, a 28-day administration of cotadutide was associated with greater reductions in fasting glucose levels (−2.48 mmol/L), glucose AUC during MMTT (−32.6%), and body weight (−4.2%) (all P<.001>
- Small sample size and short follow-up period.