Baqsimi™ (glucagon) nasal powder


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Hypoglycemia Risk Factors

Iatrogenic hypoglycemia in diabetes is related to conventional risk factors or risk factors due to compromised hypoglycemia defenses.

Detailed Information


The physiological response to decreasing PG concentrations in a healthy individual include

  • a decrease in insulin secretion from the β-cell, and

  • an increase in glucagon secretion from the α-cell.1

In the case of β-cell failure in T1DM and advanced T2DM, a decrease in PG does not result in a decrease in insulin secretion from the β-cell. The absence of this signal results in no increase in glucagon secretion from the pancreatic α-cell during hypoglycemia.1,2

Hypoglycemia is common in individuals treated with exogenous insulin and insulin secretagogues that increase insulin concentrations regardless of the PG concentration.1-3

Figure 1. Severe Hypoglycemia is a Risk in All Individuals on Insulin, Regardless of the Type of Diabetes1,2

Abbreviations: T1D = type 1 diabetes; T2D = type 2 diabetes.

Hypoglycemia Risk Factors

Iatrogenic hypoglycemia in diabetes is related to 

  • conventional risk factors of therapeutic hyperinsulinemia, or

  • risk factors due to compromised hypoglycemia defenses against falling plasma glucose concentrations.1,3

Conventional risk factors for hypoglycemia include

  • wrong dose, type, or dose timing of insulin, SUs, or glinides

  • decrease in exogenous glucose delivery due to a missed meal or fasting

  • decrease in endogenous glucose production, such as after alcohol intake

  • increase in glucose utilization, for example after exercise

  • increase in insulin sensitivity experienced late after exercise or with weight loss, and 

  • decrease in insulin clearance as a result of renal failure, hepatic failure, hypothyroidism, high level of insulin-binding antibodies.3

Risk factors due to compromised hypoglycemia defenses include

  • absolute endogenous insulin deficiency yielding loss of the glucagon response

  • history of severe hypoglycemia, impaired awareness, or both, known as hypoglycemia-associated autonomic failure, and 

  • intensive glycemic therapy and lower glycemic goal.3


1. Cryer PE. Minireview: glucagon in the pathogenesis of hypoglycemia and hyperglycemia in diabetes. Endocrinology. 2012;153(3):1039-1048.

2. McCrimmon RJ, Sherwin RS. Hypoglycemia in type 1 diabetes. Diabetes. 2010;59:2333-2339.

3. International Hypoglycaemia Study Group. Minimizing hypoglycemia in diabetes. Diabetes Care. 2015;38(8):1583-1591.


PG = plasma glucose

T1DM = type 1 diabetes mellitus

T2DM = type 2 diabetes mellitus

Date of Last Review: August 09, 2018

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