New Medication in Diabetes Treatment (S1/#2)


People living with diabetes, in particular people with Type 1 Diabetes (T1D), there are still Glycaemia unmet needs: insufficient glycaemic control; risk of severe hypoglycaemia; weight gain; glucose variability. The impact of all of these on the quality of life and the chronic complications of diabetes luring around the corner, thus putting the burden of the day to day glycaemia management on the individual.

Solutions that may help to deal better with the aforementioned needs:

Going back to the definitions of Hypoglycaemia of the International Society for Pediatric & Adolescents Diabetes (ISPAD), there are three layers of hypoglycaemia: 

 Clinical Hypoglycaemia alert: ≤70 mg/dL (3.9 mmol/L) 
Requires attention to prevent hypoglycaemia 
 Clinically important or serious hypoglycaemia: <54 mg/dL (3.0 mmol/L) 
Neurogenic symptoms & cognitive dysfunction occurs below this level with subsequent increased risk of severe hypoglycaemia. 
 Severe Hypoglycaemia: no glucose threshold specified 
An event associated with severe cognitive impairment (including coma and convulsions) requiring external assistance by another person to actively administer carbohydrates, glucagon, or take other corrective actions. 

Additionally, Severe Hypoglycaemia Is Life Threatening and Has Negative Acute: ACUTE SYMPTOMS (Neuroglycopenic, Autonomic); COGNITIVE IMPAIRMENT; IMPAIRMENT WORK PERFORMANCE & SOCIAL ACTIVITIES; ACUTE MORBIDITY (Accidents & injuries, Comas & seizures, Cardiovascular events, Cerebrovascular events); & MORTALITY and Long-term consequences: Fear of Hypoglycaemia & many people back off in insulin titrations, thus resulting in insufficient glycaemic control; affecting the Quality of Life; Driving & Employment Restrictions; Cognitive Decline; & Mortality. 

1. Injectable Glucagon

Administering Injectable Glucagon involves several steps: 
 Preparation- remove cap from vial; pull needle cover off syringe. 
 Reconstitution- inject entire contents of syringe into vial; shake gently until all powder is dissolved.  Dosing- inspect to ensure solution is clear & colourless; draw glucagon into syringe (and ensure there are no bubbles). 
 Injecting- clean site with alcohol swab (if available), inject at 90° into the tissue under cleansed area. 

Administering Injectable glucagon is multistep process that requires attention and training on the part of the caregiver. Glucagon should be kept in the fridge and reconstitution before administration.

2. Nasal Glucagon for severe Hypoglycaemia

 Nasally administered by powder (glucagon 3 mg) 
 Compact, portable, single-use drug/device combination 
 Ready to use; no reconstitution required 
 Passively absorbed in the nose, no need to inhale 
 Can be used in the presence of nasal congestion 
 Designed to be stored at room temperature (up to 86°F [30°C] 

Nasal Glucagon is available for the treatment of severe hypoglycaemia in adults, children and adolescents with Diabetes. 

3. Adjunct therapies: GLP1 Receptor Agonists

What is rational about using these drugs in people with Type 1 Diabetes (these are drugs used in people with Type 2 Diabetes and that have a lot of effect on the Beta cell). People with Type 1 Diabetes typically have lost their Beta cells and there are a lot of effects that can be of interest, for instance: 
 Reduction in hepatic glucose output (reduced glucagon levels); 
 Delaying gastric emptying; 
 Reduced postprandial hyperglycaemia;
 Reduced insulin dose; 
 Mainly reducing appetite & inducing weight loss or achieving weight maintenance & preventing weight gain; 
 Reduced risk of hypoglycaemia.

GLP1 Receptor Agonist as adjunct therapies provide benefits, but more research needed to convince fully that there are useful.

4. Adjunct therapies: SGLT2 inhibitors

 Hypoglycaemia, weight gain and glucose variability weigh on quality of life of people with Type 1 Diabetes (T1D); 
 SGLT inhibitors are promising adjunct therapies in T1D; 
 The right balance between metabolic improvements & potential side effects such as increased risk of DKA or increased burden to the patient needs to be found.

SGLT2 inhibitors can be prescribed to someone with T1D who is an Adult; following instructions; with lower HbA1c (9-10%); having higher enough doses of insulin- >20units/day; and following European Medicines Agency (EMA) having BMI >27kg/m² and most importantly EDUCATION! EDUCATION! EDUCATION!

Educational components of a risk mitigation strategy when introducing SGL2 inhibitors for Type 1 Diabetes (TID):

Patient Education: on how to avoid Diabetic Ketoacidosis and what to do in case of ketones 

Clinical Education: all prescribing clinicians should acquire full understanding of the safe use & risks associated with SGLT-inhibitor therapy (on how to detect ketones in individuals with T1D on SGLT-inhibitors and what to do in case of a threat of Diabetic ketoacidosis).

Bottom line

Prevention of Diabetic Ketoacidosis in individuals with T1D using SGLT2 inhibitors should be to:
1. Avoid dehydration (caution with strenuous sports, long periods of fasting); 
2. Avoid low carb diets 
3. Stop the SGLT2 inhibitor in case of illness (COVID-19!), surgery 
4. Measure ketones when unwell or in doubt.

Avoiding progression from ketosis to DKA: when ketones are elevated

 Hydrate 
 Supplement of insulin and to avoid hypoglycaemia: take in carbohydrates 
 Stop the SGLT2 inhibitors 
 Contact diabetes team (mention SGLT2-inhibitor) 

SGL2-inhibitors as an adjunct therapy provides benefits, but DKA remains an issue.

Curtsey of CHANTAL  MATHIEU, MD, PhD, Endocrinology



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