Summary: In a small randomised crossover infusion study of 8 adults with type 2 diabetes, acute exenatide-glucagon co-infusion increased myocardial glucose uptake in 7 of 8 participants (median 9.2 to 20 x10-3 micromol/g/min, P<0.05) and raised left ventricular peak diastolic circumferential strain rate (0.619 to 0.686 1/s, P<0.05). The change in global longitudinal strain was not significant (P=0.123). These are acute mechanistic signals, not evidence of clinical benefit.
PICO Summary
| Element | Detail |
|---|---|
| Population | 8 adults with type 2 diabetes (mean age 52 +/- 12 years, BMI 31 +/- 4 kg/m2); randomised crossover acute infusion study, United Kingdom. |
| Intervention | Single-visit exenatide-glucagon co-infusion (exenatide loading dose 50 ng/min for 30 min then 25 ng/min; glucagon 12.5 ng/kg/min); imaging by 18F-FDG PET-MRI. n=8. |
| Comparison | Within-participant control visits using 0.9% saline (and a glucagon-alone visit); each participant served as their own control. n=8. |
| Outcome | Myocardial glucose uptake increased in 7/8 (88%): median 9.2 to 20 x10-3 micromol/g/min, z=2.24, r=0.79, P<0.05. Peak diastolic circumferential strain rate rose 0.619 to 0.686 1/s, z=2.37, r=0.84, P<0.05. Global longitudinal strain changed by 0.6% (-16.0% to -16.6%), z=-1.54, r=-0.54, P=0.123 (non-significant). No 95% confidence intervals, absolute risk reduction or number needed to treat were reported for this mechanistic study. |
Expert Commentary
This is an early mechanistic experiment, not a treatment trial, and it should be read as hypothesis-generating rather than practice-informing. Eight participants received an acute single-session infusion, with each person acting as their own control across saline, glucagon and exenatide-glucagon visits. Within that frame, the co-infusion was associated with higher myocardial glucose uptake and a higher peak diastolic circumferential strain rate, both reaching nominal statistical significance, while global longitudinal strain was unchanged. The most important caveat is scale and exposure: with only eight people studied during a brief infusion, these findings cannot speak to whether sustained dual GLP-1/glucagon receptor agonism improves diastolic function, prevents heart failure or alters any patient-relevant outcome. Imaging-derived strain shifts are surrogate measures whose clinical meaning here is uncertain, and the absence of confidence intervals limits precision. Industry involvement is also relevant: authors were affiliated with the manufacturer developing these agents and with the imaging contract organisation, which warrants cautious interpretation of an open mechanistic signal. Can I use this with my patients? Not yet. There is no patient for whom acute exenatide-glucagon infusion is a usable intervention outside research. The honest read is that this supports further study of dual agonists for cardiometabolic risk, and adequately powered, outcome-driven trials are needed before any clinical claim can follow.
References
Goodman J, Schain M, Di Stefano G, et al. Exenatide and glucagon co-infusion increases myocardial glucose uptake and improves markers of diastolic dysfunction in adults with type 2 diabetes. Sci Rep. 2025;15(1):21404. doi:10.1038/s41598-025-04559-3
