Mini-Doses of Glucagon: A New Method for Treating Hypoglycemia

Hypoglycemia, or blood sugar that is lower than 4.0 mmol/L, is the most common complication in the treatment of type 1 diabetes (T1D). This condition affects the quality of life of people with T1D who experience it repeatedly. 

Hypoglycemia can manifest through unpleasant symptoms such as fatigue, sweating, tremors and palpitations. It must be treated promptly to prevent severe hypoglycemia and protect the brain from the impact of a lack of sugar (e.g., lack of concentration). 

The current recommendation for treating hypoglycemia is to take 15 g of fast sugars (e.g. Dex 4, juice, Rockets candy) and repeat every 15 minutes as needed.

However, several studies have shown that the amount of sugar taken often exceeds this recommendation, leading to the opposite effect: hyperglycemia. What’s more, preventing or treating hypoglycemia by consuming carbohydrates can lead to long-term weight gain.

But it may be possible to use a different method of treatment. Indeed, a study published in April 2023 suggests that it may be possible to take mini-doses of glucagon.

Mini-doses of glucagon

The study was conducted by Danish researchers with 24 adults with T1D who use an insulin pump. The goal was to study the use of a new form of injectable, ready-to-use glucagon called Dasiglucagon Unlike other injectable types of glucagon, Daiglucagon doesn’t need to be reconstituted, making it easier to use.

The researchers looked at how the consumption of fast sugars compared with the injection of mini-doses of this new glucagon to treat or prevent non-severe hypoglycemia (between 3.0 and 3.9 mmol/L). 

For the purposes of the clinical trials, participants were instructed to inject a small, predefined dose of 80 μg (micrograms) of Dasiglucagon using a reusable pen. This dose is equivalent to one tenth of a regular adult dose.

The U.S. Food and Drug Administration (FDA) has authorized Dasiglucagon for the treatment of severe hypoglycemia with an auto-injector pen (similar to an Epipen) available on the market under the name Zegalogue. Clinical trials are still underway in Canada.

A faster, more efficient, lower-calorie method

Study participants who injected mini-doses of glucagon to treat hypoglycemia recovered 44% faster and consumed 11% fewer carbohydrates (i.e. 20 g less) daily than those who followed the traditional treatment with quick-acting carbohydrates only. They were also more successful in preventing hypoglycemia. The researchers noted no difference in rebound hyperglycemic episodes. It’s worth noting that the participants who were instructed to use glucagon were also allowed to consume fast sugars when injecting glucagon wasn’t practical or possible for them.

A proportion of 96% of participants said they were in favour of using glucagon to manage hypoglycemia in the future, confirming that this treatment is well tolerated. Mild nausea was the most frequent adverse effect.

The treatment of hypoglycemia has been widely researched in recent years. Although the cost of ready-to-use glucagon is likely to be higher than that of fast sugars, the use of mini-doses seems like a promising avenue that could improve the quality of life of people with T1D. By reducing the consumption of carbohydrates to correct hypoglycemia, it may be easier to prevent weight gain and possibly limit blood sugar variations. It’s also a great alternative for those who aren’t necessarily hungry when their blood sugar is low, those who have difficulty ingesting carbohydrates, or those who suffer from gastroparesis (impaired digestion caused by T1D).

References :

• Laugesen, C.et al. (2023) Pen-administered low-dose dasiglucagon vs usual care for prevention and treatment of non-severe hypoglycaemia in people with type 1 diabetes during free-living conditions: a Phase II, randomised, open-label, two-period crossover trial. Diabetologia (2023). https://link.springer.com/article/10.1007/s00125-023-05909-4
• Brutsaert. E.F. (2022) Hypoglycémie. Le maule Merck – Version pour le grand public. https://www.merckmanuals.com/fr-ca/accueil/troubles-hormonaux-et-m%C3%A9taboliques/diab%C3%A8te-sucr%C3%A9-ds-et-troubles-du-m%C3%A9tabolisme-de-la-glyc%C3%A9mie/hypoglyc%C3%A9mie
• Radermecker, R. P. et al. (2008). Le cerveau, un organe gluco-dépendant : effets délétères de l’hypoglycémie et de l’hyperglycémie. Rev. Med. Liège 63(5-6):280-286. https://orbi.uliege.be/bitstream/2268/4211/1/20080506_09.pdf
• Diabète Québec (2018). L’hypoglycémie chez la personne diabétique. Page consultée le 30 mai 2023. https://www.diabete.qc.ca/fr/vivre-avec-le-diabete/soins-et-traitements/hypoglycemie-et-hyperglycemie/lhypoglycemie-chez-la-personne-diabetique/