Glucagon and GLP-1 are both peptide hormones involved in blood sugar regulation, which leads to a reasonable but mistaken assumption that they do similar things. In fact, they work in opposite directions, and understanding that contrast is key to understanding why some of the newest obesity drugs deliberately combine both.
Where Each Hormone Comes From
Glucagon is produced by the alpha cells of the pancreas. GLP-1 (glucagon-like peptide-1), despite the overlapping name, is produced primarily by L-cells in the lining of the small intestine, released in response to eating. The shared name reflects a structural relationship, both are proteolytic products of related precursor genes, not a shared function.
What Each One Does
Glucagon is the body's primary hormone for raising blood sugar when it drops too low, signaling the liver to release stored glucose. GLP-1 does essentially the opposite in a glucose-dependent way: it stimulates insulin release from the pancreas when blood sugar is elevated, suppresses glucagon release at the same time, slows stomach emptying, and signals satiety centers in the brain to reduce appetite. In short, glucagon raises blood sugar during a shortage, while GLP-1 lowers blood sugar and appetite after a meal.
How Each Is Used Medically
Glucagon, as detailed in this site's dedicated guide, is an FDA-approved emergency rescue treatment for severe hypoglycemia, typically in people with diabetes who take insulin. GLP-1 receptor agonists, including semaglutide and tirzepatide, are FDA-approved for type 2 diabetes and, at higher doses, chronic weight management, used as ongoing daily or weekly treatments rather than emergency rescue drugs.
The Apparent Paradox: Why New Obesity Drugs Add Glucagon Back In
Several next-generation obesity drug candidates now in development, including survodutide, mazdutide, cotadutide, and retatrutide, are "dual" or "triple" agonists that deliberately activate the glucagon receptor in addition to the GLP-1 receptor (and, for some, the GIP receptor as well). This seems counterintuitive: why add a hormone that raises blood sugar to a drug meant to treat diabetes and obesity?
The answer lies in a different glucagon effect beyond its acute blood-sugar-raising action: at the receptor level, glucagon signaling in the liver and fat tissue is associated with increased energy expenditure and fat oxidation, meaning the body burns more stored fat for energy. In these combination drugs, the GLP-1 (and GIP) component's strong insulin-stimulating, appetite-suppressing effects are intended to offset glucagon's glucose-raising tendency, while glucagon's metabolic, fat-burning contribution adds to the weight-loss effect beyond what GLP-1 agonism alone achieves. Clinical trial data for these combination candidates, discussed in their individual guides and comparison articles elsewhere on this site, generally show larger weight-loss percentages than GLP-1-only drugs, consistent with this added mechanism, though with their own distinct side-effect considerations.
The Bottom Line
Glucagon and GLP-1 are not variations on the same theme; they are counter-regulatory partners that normally balance each other to keep blood sugar in a stable range. Their shared name is a frequent source of confusion, but understanding their opposite core functions is exactly what makes the newest generation of combination obesity drugs make sense, rather than seem contradictory.