Frontiers in Pharmacology (Sep 2025)
The macrogol revolution in the treatment of chronic constipation. A short history of laxatives
Abstract
The difficulty of treating constipation has accompanied humanity through the centuries. Until 1990, numerous remedies were proposed to alleviate the condition; however, due to their aggressive nature or side effects, they were mainly used occasionally or for short periods. When used chronically, there was a high risk of adverse events, sometimes even severe ones. Macrogol, a polyethylene glycol polymer of 3,500–4,000 Daltons, due to its unique physicochemical water binding properties, has revolutionized the treatment of constipation. Macrogol bound to water molecules passes through the entire gastrointestinal tract without being absorbed and metabolized, and without causing significant absorption of water or electrolytes. It is not toxic and does not affect the colonic mucosa. Ultimately, the macrogol-water structure remains unchanged during its transit through the gastrointestinal tract, and, carrying its bound water, increases the luminal volume in the colon with a scarce osmotic effect in the gut lumen. Notably, it has mild adverse effects and no severe adverse effects even when administered long-term or in large amounts. Macrogol changed the paradigm of constipation treatment in the ‘90s. In the macrogol era, it is now possible to initiate treatment in functional, organic, and secondary constipation. In the macrogol era, the chronic constipation algorithm has shifted to become therapeutic first, then diagnostic, without risks for the patient, who can immediately benefit from the treatment. Macrogol offers the possibility to perform long-term treatment, to be safely used in children, in elderly subjects, during pregnancy, and in the presence of irreversible secondary and organic constipation.
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