Summary: In eight adults with type 2 diabetes, a single acute co-infusion of exenatide plus glucagon raised myocardial glucose uptake (median 9.2 to 20 x10 micromol/g/min in 7 of 8 participants, P<0.05) and modestly improved one diastolic marker, the left ventricular peak diastolic circumferential strain rate (0.619 to 0.686 1/s, P<0.05), versus saline. Global longitudinal strain did not change significantly (P=0.123). This is an early mechanistic signal, not evidence of clinical benefit.
PICO Summary
| Element | Detail |
|---|---|
| Population | Eight adults with type 2 diabetes (mean age 52 plus or minus 12 years, mean BMI 31 plus or minus 4 kg/m2); single-centre experimental medicine study, United Kingdom. |
| Intervention | Acute intravenous exenatide:glucagon co-infusion (exenatide 50 ng/min loading for 30 min then 25 ng/min; glucagon 12.5 ng/kg/min) during one of three randomised visits; n=8, within-subject crossover, assessed by 18F-FDG PET-MRI. |
| Comparison | 0.9% saline infusion visit (and a glucagon-alone visit) in the same eight participants; within-subject comparator, n=8. |
| Outcome | Myocardial glucose uptake rose in 7/8 (88%), median 9.2 to 20 x10 micromol/g/min (z=2.24, r=0.79, P<0.05). LV peak diastolic circumferential strain rate rose 0.619 to 0.686 1/s (z=2.37, r=0.84, P<0.05). LV global longitudinal strain changed only numerically, -16.0% to -16.6% (z=-1.54, r=-0.54, P=0.123, non-significant). No 95% confidence intervals, absolute risk reduction, or NNT reported; outcomes are physiological, not clinical events. |
Expert Commentary
This is a small acute mechanistic study, and its findings should be read as a proof-of-concept signal rather than as proven cardiac benefit. Eight participants underwent within-subject infusions, and the imaging endpoints were surrogate measures: myocardial glucose uptake on PET and a single diastolic strain-rate marker on MRI. A statistically significant rise in glucose uptake and in diastolic circumferential strain rate was observed, yet the global longitudinal strain change did not reach significance, and no patient-relevant outcomes such as heart failure events, symptoms, or exercise capacity were assessed. The dominant limitation is the sample of eight with no chronic dosing, so durability, safety over time, and whether these acute shifts translate into structural or prognostic change all remain unknown. The study was supported by manufacturer-affiliated investigators from a pharmaceutical company and an imaging contract organisation, which warrants cautious interpretation of an unblinded physiological readout. Can I use this with my patients? Not yet. There is no patient in routine type 2 diabetes care for whom an intravenous exenatide-glucagon co-infusion is an option, and these data do not change current heart failure or glucose-lowering practice. The result is best viewed as justification for larger, longer, blinded trials with hard endpoints. One would want to see whether a chronically dosed dual GLP-1/glucagon agonist improves diastolic function and outcomes before any clinical claim is made.
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
