Partial restoration of counterregulatory circulating glucagon by dapagliflozin and low-dose glibenclamide in men with type 1 diabetes: in vitro studies and randomised clinical crossover trial

What Was Tested

This randomized controlled trial paper looks at Glucagon.

Excessive secretion of somatostatin from neighbouring delta-cells (which are sensitive to the SGLT2 inhibitor dapagliflozin) also causes inappropriate paracrine inhibition of glucagon secretion at low glucose levels.

Supported by The Leona M. and Harry B.

Who Took Part

The study group was 12 participants.

The age groups tagged for this paper are adults and middle-aged adults, men only.

This was assessed using a hyperinsulinaemic-hypoglycaemic clamp in 12 male participants with T1D, with responses from 6 healthy controls (4 males and 2 females) serving as a reference.

The primary endpoint was the change in plasma glucagon levels during hypoglycaemia from baseline (no medication) to post-treatment (glibenclamide or dapagliflozin).

How the Study Was Run

The researchers set it up as a randomized and crossover study.

Because people in this Glucagon study were split into groups at random, differences between the groups are less likely to reflect who happened to join each one.

Each person switched between Glucagon and the comparison at some point, usually with a gap in between.

All participants were included in the analyses.

The study is registered with ISRCTN (58098350).

What Was Measured

Excessive secretion of somatostatin from neighbouring delta-cells (which are sensitive to the SGLT2 inhibitor dapagliflozin) also causes inappropriate paracrine inhibition of glucagon secretion at low glucose levels.

The subject headings attached to it are Benzhydryl Compounds, Glucagon, Diabetes Mellitus, Type 1, Glyburide, Glucosides, Hypoglycemic Agents and Islets of Langerhans.

The authors tagged it with the keywords Dapagliflozin, Glibenclamide, Glucose infusion rate, Hypoglycaemia and Type-1 diabetes.

What This Means in Plain Language

The paper is a randomized and crossover study of Glucagon in 12 participants.

With fewer than 40 people, it is a small study, so it is better read as an early signal for further research than as a settled answer.

Results are reported in around 12 sentences of the abstract; we leave them to the paper itself rather than summarise them.

The publication is from 2026 (EBioMedicine), a journal based in Netherlands.

More context: the Glucagon compound page, all human trials.