Stable Liquid Glucagon: Beyond Emergency Hypoglycemia Rescue

Abstract

Glycemic control is the mainstay of preventing diabetes complications at the expense of increased risk of hypoglycemia. Severe hypoglycemia negatively impacts the quality of life of patients with type 1 diabetes and can lead to morbidity and mortality. Currently available glucagon emergency kits are effective at treating hypoglycemia when correctly used, however use is complicated especially by untrained persons. Better formulations and devices for glucagon treatment of hypoglycemia are needed, specifically stable liquid glucagon. Out of the scope of this review, other potential uses of stable liquid glucagon include congenital hyperinsulinism, post-bariatric surgery hypoglycemia, and insulinoma induced hypoglycemia. In the 35 years since Food and Drug Administration (FDA) approval of the first liquid stable human recombinant insulin, we continue to wait for the glucagon counterpart. For mild hypoglycemia, a commercially available liquid stable glucagon would enable more widespread implementation of mini-dose glucagon use as well as glucagon in dual hormone closed-loop systems. This review focuses on the current and upcoming pharmaceutical uses of glucagon in the treatment of type 1 diabetes with an outlook on stable liquid glucagon preparations that will hopefully be available for use in patients in the near future.

Is the new “energetic feedback” for insulin delivery monitoring available in any acute severe glucose metabolism disorders?

“…Correlation between ∆T and glycaemia was not calculated considering the probable discordance in time of the two parameters. [7][8][9]16 Data have been collected mainly in the ICU service of the Moscow Emergency Institute named by VN. Sklifossovski, from 2001 till 2016 years with the agreement of the Russian Federation Ministry of Health.…”

“…Up to now glycaemia measure remains the only criterion used for the treatment management of hyperglycaemia in diabetic or critically ill (ARDS, shock) patients and in spite of interesting innovations including glucagon administration, artificial pancreas, close loop use and others, hypoglycaemia episodes and yo-yo events are still a problem during insulin therapy. [1][2][3][4][5][6] According to some authors [7][8][9] and our previous observations, glycaemia reaction is too slow to reflect the real metabolism situation. Hence the correction is started a little late, excessive doses administration and answers to them cannot be avoided, even if mathematic anticipation is provided, and that cause the aforementioned events.…”

“…Hence the correction is started a little late, excessive doses administration and answers to them cannot be avoided, even if mathematic anticipation is provided, and that cause the aforementioned events. [7][8][9] Besides, glycaemia is known to be the result of the difference between glucose production and utilization which depend on many changing factors, such as external glucose intake, internal hormonal influences, neo gluconeogenesis, physical and intellectual activities. Taking into account that 70% of the energy used by the organism comes from glucose turn over 10 it was likely that the basal metabolism evolution could better reflect the organism needs in insulin and glucose than glycaemia measure, allowing anticipation of its fluctuations.…”

How Important Is a Closed‐Loop Artificial Pancreas?

“…CLAP systems using only insulin is called a uni‐hormone system, or insulin and glucagon and in such a case it is called dual‐hormone system and may be more efficient in reducing the risk of hypoglycemia . Studies toward development of stable glucagon formulations are in progress, but at the moment there is lack of commercially available stable liquid glucagon which limits the use of dual‐hormone systems.…”

Is Mini-Dose Glucagon the Answer to Preventing Exercise-Related Dysglycemia?

“…To address this issue, multiple companies have developed stable forms of glucagon. These companies include Xeris Pharmaceuticals (G-Pen), Zealand Pharma (dasiglucagon), and Adocia (BioChaperone glucagon) (5). The development of these stable forms of glucagon has opened up the possibility of uses beyond rescue, including mini-dose glucagon (6-8) and automated glucagon delivery (9).…”