Table 2.
Possible Side Effects of Glucagon
| Site | Impact | Mechanism | Comments |
|---|---|---|---|
| Gastrointestinal | Nausea and vomiting. | Inhibition of gastric motility. | Common side effects to the 1 mg hypoglycemia rescue dose of glucagon, but much less common at the micro-dosing level used in dual-hormone systems. |
| Metabolism | Potential decrease in plasma triglyceride and cholesterol levels. Administration of high dose increases resting metabolic rate. | Promotes triglyceride lipolysis to produce free fatty acids and hepatic fatty acid oxidation for fuel substrates.70 | In short-term human studies: administration of exogenous glucagon appears to have little effect on plasma lipid levels in healthy subjects or in subjects with T1D.71,72 |
| In a rat model: administration of glucagon over 21 days decreased plasma triglyceride and cholesterol levels with no change in liver fat.73 | |||
| In healthy subjects, glucagon infusion, along with a somatostatin infusion to inhibit insulin secretion, increased the resting metabolic rate by 15%.74 | |||
| Cardiovascular | Administration of high dose glucagon can induce small increases in mean arterial pressure and heart rate without major effects of systemic vascular resistance.75 | At doses of >1mg of glucagon, glucagon acts directly on cardiac tissues with chronotropic and inotropic effects via stimulation of catecholamines. | Older animal studies showed a detrimental effect of high dose glucagon on ischemic myocardium.76,77 |
| Human studies showed benefit or no effect of high dose glucagon in myocardial ischemia.78,79 | |||
| Central nervous | Administration of high dose glucagon elicits feeling of satiety. | Glucagon crosses the blood brain barrier effecting the vagal system. | In one study, pre-prandial 1mg IM doses of glucagon over two weeks in healthy adults resulted in a reduction in intake of 440 calories per day and an average weight loss of 0.45 lbs compared to weight gain of 3.4 lbs in the placebo arm.80 |
| Urinary | Increased natriuresis. | Possibly mediated by renal arterial vasodilation with an increase in renal blood flow.70 | |
| Respiratory | Pulmonary bronchodilation. | Smooth muscle relaxation. |