Dr Louise Johnson explains why it’s good news that a nasal glucagon, sold under the name Baqsimi, was approved in July by the US FDA. The bad news is that it will be some time before it is available in South Africa.
Baqsimi, manufactured by Eli Lilly, is the first nasal glucagon approved for the emergency treatment of severe hypoglycaemia that can be administered without an injection.
The risk of hypoglycaemia
Millions of people living with diabetes are on insulin to control their blood glucose levels and to prevent long-term complications of diabetes.
Insulin can cause hypoglycaemia (low blood glucose), potentially severe and even life-threatening complications that burdens insulin users each day1.
The risk is relevant to all Type 1 diabetes patients and 30% of Type 2 diabetes patients receiving insulin treatment.
Severe hypoglycaemia is defined as an episode of low blood glucose, wherein a person with diabetes requires assistance from a third party to treat the episode.
In the T1D Exchange Patient Registry, it was indicated that this occurs more frequently than previously thought2.
The fear of another hypoglycaemic episode often leads to reduced glucose control to allow glucose to remain higher than desired. This increases the risk of both microvascular and macrovascular complications3.
It’s acknowledged that, if it was not for the fear of hypoglycaemia, people with diabetes could have normal to near normal glucose levels and avoid the complications of hyperglycaemia (high blood glucose).
Challenges with management of severe hypoglycaemia
Glucagon hypo kit
Glucagon is the treatment of choice in severe hypoglycaemia. It is very unstable in the liquid form and is therefore available in a hypo kit.
This kit consists of a pre-filled liquid syringe and a vial of dry powder. It must be mixed by the third party who then administers the treatment during an episode of severe hypoglycaemia.
It can be very daunting for the third party, usually a non-medical person, to observe the person with diabetes having hypoglycaemic seizure or being in a hypoglycaemic coma.
In a study, in which parents of children with Type 1 diabetes used a glucagon hypo kit in a simulated emergency hypoglycaemia, it showed that the parent took between two minutes and 12 minutes to get the solution ready and inject it into a piece of meat (to simulate a thigh muscle).
The study consisted of 136 parents who were all trained before the study. The data shows that despite the training, 69% of the parents had trouble with the hypo kit.
These were all handling difficulties, such as opening the pack, removing of the needle sheath, mixing the ingredients and bending needles4.
The great concern in this study was that 6% aborted the injection entirely and 4% injected only air or water from the prefilled syringe.
This data clearly indicates the need for a better, safer and easier way of giving glucagon in an emergency.
A unique and critical aspect of glucagon use is the intended user. Unlike insulin, a third party gives glucagon. This is the co-worker, teacher, friend, child, sport coach, etc. This is almost never a trained medical professional.
The previous study clearly shows that this leads to suboptimal use of otherwise effective medication, delays in treatment and costly use of emergency services and hospitalisation.
In 1983, it was shown that glucagon administered with a carrier drug, such as sodium glycocholate, could raise blood glucose levels when administered as intranasal drops.
Despite promising data, research into nasal glucagon was minimal. Reasons are debatable. Some of the reasons given are the fact that the market is very small for this drug and new promising drugs, such as the SGLT2 inhibitors, came onto the market and many more.
In recent years though, there was renewed interest to address the unmet need for a glucagon delivery system that is easy for healthcare providers to teach and easy for caregivers and third parties to administer.
Baqsimi is a dry powder glucagon formulation in a compact, highly portable, single-use nasal powder dosing device that allows for a single-step nasal administration.
The caregiver simple inserts the device into the nasal opening and fully depresses the plunger. This gently expels the powder into the nasal cavity.
The product has been designed that no breathing is necessary as it is absorbed from the nasal mucosa. The dosage is a fixed 3mg dosage for all people with diabetes from four years of age.
What are the side effects of Baqsimi?
- Nasal irritation (runny nose, congestion, sneezing, cough, nasal bleed) – 12,4% people experienced these side effects. The nasal irritation in injectable glucagon was only 1,3%.
- Nausea (26%), headache (18%), vomiting (15%). These last three side effects were also experienced in intramuscular injected glucagon preparations in 33,8%, 9,3%, and 13,9%.
Warnings and precautions
Intranasal glucagon should not be used in persons with hypoglycaemia of chronic nature due to starvation; low adrenal gland functioning (Addison’s disease); insulinoma (tumour of pancreas) or pheochromocytoma (tumour of adrenal gland tissue (which produces catecholamine and where glucagon can cause a dangerously high blood pressure)).
Previously allergic reaction to glucagon with injectable form should be avoided.
It also carries a warning that it should not be used in those that have been fasting for long periods. The reason for this is that it causes low levels of reusable glucose in the liver.
Patients taking beta-blockers may have a transient increase in blood pressure and pulse rate when given nasal glucagon.
Patients taking indomethacin may have no response to nasal glucagon, or even lower glucose. In such situations, per mouth or IV or IM glucose should be given5.
In conclusion, we can at long last be excited about an easy-to-administer drug for people with diabetes on insulin that should need this in a hypoglycaemic emergency. It will, however, still take some time to arrive in South Africa.
- Pontiroli A.E. “Intranasal glucagon: A promising approach for treatment of severe hypoglycaemia.”Journal of Diabetes Science and Technology,2015 :vol9(1) p38-43
- Beck R. et. al. ‘The T1D Exchange Clinic. Registry.’ J Clin endocrinol Metab ,2012;97 p4383-4389
- Cryer P. ‘Hypoglycemia in diabetes: Pathophysiology, Prevalence and Prevention. 2nd Alexandria V.A.: American Diabetes Association,2012
- Harris G et.al. ‘Glucagon administration –underevaluated and undertaught.’ Practical Diabetes Int 2001:18;22-25
- (GN HCP ISI 24Jul 2019 (Eli Lilly Baqsimi package insert)
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Dr Louise Johnson is a specialist physician passionate about diabetes and endocrinology. She enjoys helping people with diabetes live a full life with optimal quality. She is based in Pretoria in private practice.