|Area of validity [year of publication]|
Publisher/Title of guideline
Recommendations and instructions about macrogol (PEG)
(Note: All reference numbers within the quotations are those used in the list of references in the quoted original publication.)
|Europe  ESNM: European Society of Neurogastroenterology and Motility guidelines on functional constipation in adults||Statement 41: Saline laxatives, especially polyethylene glycol (PEG), are effective in treating symptoms of constipation in patients with chronic constipation; Level of evidence: Strong; Recommendation: Strong; Level of agreement: 100%; Current evidence and literature: The evidence supporting the usefulness of saline laxatives, especially polyethylene glycol (PEG), is strong. There are several large, high‐quality trials supporting the fact that PEG is superior to placebo in improving symptoms in patients with chronic constipation, with a NNT of 3 (95% CI 2–4).8,172–180. Moreover, a Cochrane analysis also concluded that PEG is superior to lactulose in patients with chronic constipation, resulting in more frequent stools, looser stools, and less abdominal pain. PEG also increases the number of spontaneous complete bowel movements, improves stool consistency, and reduces severity of straining, without clearly affecting abdominal pain, in patients with IBS‐C, further supporting its usefulness to treat constipation. The most common side effects with PEG are diarrhoea and abdominal pain, but not all trials find these to be more common in patients treated with PEG compared to the placebo group.|||
DGNM/DGVS: S2k-Guideline Chronic Constipation: Definition, pathophysiology, diagnosis and therapy
Statement 5-1; Conventional drug treatment (conventional “laxatives”) (Strong consensus)
Macrogols, sodium picosulfate and bisacodyl should be used as first-line medication. There is no justification for limiting their period of use. They can also be used in pregnancy.
Comment: Macrogol, bisacodyl and sodium picosulfate are effective and safe in acute functional and chronic constipation and are among the agents of first choice. This also applies to pregnancy. In chronic constipation, the dosage and frequency of ingestion are governed by individual requirements. The choice with regard to the form of administration (coated tablets, drops, soluble (oral) powder) and taste, is based on patient preference. The efficacy and safety of macrogol (=PEG=polyethylene glycol 3350 or 4000) in chronic constipation has been demonstrated in numerous studies. A meta-analysis  concluded that in terms of stool frequency and consistency, relief of abdominal pain and need for ingestion of laxatives, PEG is superior to lactulose (better efficacy with fewer side effects). In a comparative study, macrogol was more effective than the partial 5-HT4-agonist tegaserod . Although pregnant women were excluded from the controlled studies, there are no reservations regarding use during pregnancy . PEG undergoes only minimal absorption and is excreted in the urine unchanged . The addition of electrolytes when PEG is used as laxative is unnecessary, only with intestinal lavage or in the treatment of coprostasis. Electrolyte-free preparations taste better .
FNSC: Clinical practice guidelines from the French National Society of Coloproctology in treating chronic constipation
Osmotic and bulk laxatives remain the first-line laxative treatment for treating chronic constipation (CC), including during pregnancy (Expert Recommendation). Osmotic laxatives are recommended as a first-line treatment for constipation on the basis of their efficacy and good tolerance with the dietetic rules or as a complement to them (Level II, Grade B). They are more effective than a placebo with an increase of 2–3 stools per week and a two-fold higher success (≥3 stools/week) (Level I, Grade A). Among osmotic laxatives, polyethylene glycol is more effective than lactulose in improving the stool frequency and consistency as well as for abdominal pain (Level I, Grade A) [15–20]. Bulk laxatives can be soluble (psyllium, ispaghula, etc.) or insoluble fibres (wheat bran). These are organic polysaccharides that retain water in the intestinal lumen. They should be ingested with sufficient quantities of water [13,21,22]. They are also a first-line laxative option (Level II, Grade B). Moreover, they can improve the frequency and consistency of faeces as well as the symptoms of dyschezia. Their main side effects are meteorism and flatulence. Bulk laxatives are contraindicated in cases of intestinal stenosis, faecal impaction or inflammatory colitis.
AIGO/SICCR: Consensus statement AIGO/SICCR diagnosis and treatment of chronic constipation and obstructed defecation (part II: treatment)
Medical treatment in chronic constipation → Polyethylene glycol: level of evidence I; grade of recommendation: A
Placebo-controlled trial of PEG: PEG is an organic polymer that is not degraded by the intestinal flora. The effectiveness of PEG has been documented in numerous trials [40-44]. PEG increased the stool frequency (P < 0.01) while improving the stool consistency [40,41,43] and reducing other symptoms of constipation [41,43]. Iso-osmotic or hypo-osmotic solutions of PEG consistently improved the frequency of bowel movements compared with the frequency before treatment (P < 0.001) . PEG was well tolerated, and side effects (abdominal cramps, flatulence, nausea) were rare.
Trials of PEG vs other laxatives: PEG is more effective than lactulose [31,32] in increasing the stool frequency and improving the stool’s consistency. In patients treated with PEG, there are also lower rates of rescue medication use and flatulence. One trial showed that PEG was more effective than tegaserod . PEG is a pillar in the treatment of chronic idiopathic constipation because of its high efficacy. There is evidence that PEG provides significant benefits compared with placebos and other laxatives. Furthermore, retrospective studies show that PEG remains effective for up two years of treatment [46,47]. The use of PEG is supported by Level I evidence, Grade A recommendation.
HERPC: Guideline on Management of Constipation approved by HERPC
RECOMMENDED TREATMENT OF CONSTIPATION IN ADULTS: 2nd line: OSMOTIC LAXATIVE: Macrogols 1 – 3 sachets daily in divided doses +/– STIMULANT Laxative
Treatment of faecal impaction: 1st line (Oral): Macrogols 8 sachets daily in divided doses
WGO: World Gastroenterology Organization Global Guideline Constipation—A Global Perspective
|The second step in the graded approach is to add osmotic laxatives. The best evidence is for the use of polyethylene glycol, but there is also good evidence for lactulose.|||
AGA: American Gastroenterological Association Medical Position Statement on Constipation
|We suggest a gradual increase in fiber intake, as both foods included in the diet and as supplements and/or an inexpensive osmotic agent, such as milk of magnesia or polyethylene glycol. Depending on stool consistency, the next step may be to supplement the osmotic agent with a stimulant laxative (e.g. bisacodyl or glycerol suppositories), which is preferably administered 30 minutes after a meal to synergize the pharmacologic agent with the gastrocolonic response.|||
South Korea 
Korean Society of Neurogastroenterology and Motility: Guidelines for the Diagnosis and Treatment of Chronic Functional Constipation in Korea
24. Statement: Polyethylene glycol improves bowel frequency and stool consistency in patients with chronic constipation.
- Grade of recommendation: 1.; Level of evidence: A.
- Experts’ opinions: completely agree (73.1%), mostly agree (26.9%), partially agree (0%), mostly disagree (0%), completely disagree (0%), and not sure (0%).
25. Statement: Long-term administration of polyethylene glycol is recommended because serious adverse reactions are rare.
- Grade of recommendation: 1.; Level of evidence: A.
- Experts’ opinions: completely agree (50.0%), mostly agree (50.0%), partially agree (0%), mostly disagree (0%), completely disagree (0%), not sure (0%).
Asociacion Mexicana de Gastroenterología. The Mexican consensus on chronic constipation
24. Polyethylene glycol is the most widely studied laxative in functional constipation (FC) and has been shown to increase defecation frequency and improve stool consistency.
Quality of evidence and strength of recommendation: A1 strong, in favour of the intervention (in complete agreement: 86%; in partial agreement: 14%).
Polyethylene glycol (PEG 3350) is an organic polymer whose osmotic activity is proportionate to the number of monomers that form it. It is metabolically inert, not metabolized or degraded by colonic bacteria, and interacts with water in a solution to increase osmotic pressure. There are multiple studies that demonstrate the effectiveness of PEG over placebo, lactulose, and other laxatives in the treatment of FC.113–118 In a recent meta-analysis,119 19 studies were evaluated (9 with PEG alone, 8 with PEG plus electrolytes, and 2 that compared PEG vs PEG plus electrolytes), demonstrating that the administration of PEG (with and without electrolytes) increased the number of bowel movements per week and softened stool consistency. According to the 2010 Cochrane review,120 PEG is superior to lactulose in increasing defecation frequency, softening stool consistency, and reducing the need for rescue laxatives. The NNT has been estimated at 3 (95% CI: 2–4) and the majority of the studies had less bias and heterogeneity than the studies on other drugs. The side effects reported were infrequent and the most common were abdominal pain and headache. Even though most of the studies had a follow-up under 6 months, PEG effectiveness did not appear to decrease after that period of time. The recommended dose is 17 g of PEG diluted in at least 250 ml of water.
Latin America 
Latin American Consensus on Chronic Constipation
Polyethylene glycol (PEG) has demonstrated effectiveness and safety in well-designed studies in patients with Chronic constipation [CC] (grade A recommendation).
There are no studies evaluating lactulose in the management of CC during the last 10 years and the only recent evidence suggests that it is less effective than PEG. However, given that previous studies were considered acceptable, the Consensus did not disapprove its use when required (grade C recommendation). Agents in this group include nonabsorbable sugars (lactulose), saline agents (magnesium hydroxide), and PEG. Lactulose clinical studies are old and have methodological limitations; however, they suggest that it is more effective than placebo52–56. Recent studies compared lactulose with PEG and, although it can be said that they have an intermediate methodological quality, PEG proved to be more effective than lactulose and it presented less adverse effects55,56 (Table V). Some well-designed studies have shown that PEG is effective in both short-term and long-term interventions (6 months) (Table VI). The dose is 17–32 g / day, with a rapid onset time of action (0.5–1 h) and the most frequent secondary event is fecal incontinence due to its laxative potency57–59. One study even compared PEG with lactulose, and showed that PEG in doses of 13–39 g / day was more effective and better tolerated in CC56. Finally, no clinical studies have been conducted with magnesium hydroxide in CC.