Insulin and Glucagon Co-administration – Optimizing Glycemic Control without Risks of Hypoglycemia

Opposing actions of insulin and glucagon may be the key to glucose control. 

The risk of hypoglycemia is of enormous concern among people with diabetes on insulin-containing regimens. These risks are even higher in those taking beta-blockers, as symptoms of low blood sugar can be masked by the drug. People of older age showing cognitive decline are also at higher risk and may not notice life-threatening drops in glucose levels when they occur. Considerable effort is required by both the patient and provider to manage and coordinate diet, activity, insulin administration, and blood glucose monitoring. Despite advancements in medicine and technology, the risk of hypoglycemia remains a significant obstacle in diabetes management.  

A new study published in the American Diabetes Association (ADA) journal, Diabetes, and presented at the ADA’s Virtual 80th Scientific Sessions, reveals how two medications’ opposing actions can be combined to optimize glycemic control.  

The study focused on patients with type 1 diabetes mellitus (T1DM). Eleven patients, aged 32 to 40 years, were treated overnight with low dose IV insulin on two occasions before morning meals. The goal was to reach near-normal fasting blood glucose and control the early rise in glucose while eliciting hypoglycemia in a later phase. The patients were then given a meal challenge consisting of 100g of carbohydrates. A phased 6-hour infusion of regular insulin was administered on each occasion, either with or without glucagon. Glucose levels were evaluated throughout the infusion period.  

When glucagon and insulin were administered concomitantly, both drugs were given at fixed molar ratios. Initially, there was no difference in meal-induced glucose elevations when taking with or without glucagon. During the later phase (final 3 hours of infusion), when patients did not take glucagon, 7 of the 11 patients experienced glucose levels below 80mg/dL requiring intravenous glucose rescue. Five of these patients experienced severe hypoglycemia of roughly 50mg/dL. 

Hypoglycemia remains an essential concern in patients with diabetes who are dependent on insulin. This study showed the favorable effects of insulin and glucagon when co-administered intravenously in T1DM patients. Results suggest that glucagon may protect against insulin-induced hypoglycemia without impeding hyperglycemic control. Although a small study, these results suggest a possible benefit to the concomitant use of these opposing medications. Insulin and glucose co-administration may be a novel approach to controlling diabetes.  However, there are very few studies currently available on the concomitant use of these two drugs. Therefore, more information is needed to determine the safety and efficacy of this treatment option in patients with T1DM. 

Practice Pearls: 

• Concomitant insulin and glucagon administration may protect against insulin-induced hypoglycemia without impeding hyperglycemic control. 
• In this study, patients who did not use glucagon began experiencing drops in blood glucose of about 50 to 80mg/dL. 
• Further research is needed to determine the safety and efficacy of these findings.  

Bode, BW., Boyd, J., Shah, A., Parkes, D., Ghosh S., Cherrington, A. 7-LB: Insulin and Glucagon Coadministration in Type 1 Diabetes Prevents Hypoglycemia without Worsening Hyperglycemia. Diabetes. Jun 2020, 69 (Supplement 1) 7-LB; DOI: 10.2337/db20-7-LB 

Melinda Rodriguez, PharmD Candidate 2021, Lake Erie College of Osteopathic Medicine – L|E|C|O|M School of Pharmacy 

See more about insulin in our therapy center, or see our exclusive 2017 interview with Dr. Bode.