Liraglutide accelerates colonic transit in people with type 1 diabetes and polyneuropathy: A randomised, double‐blind, placebo‐controlled trial

Wegeberg, Anne-Marie; Hansen, Christian Stevns; Farmer, Adam D.; Karmisholt, Jesper; Drewes, Asbjørn Mohr; Jakobsen, Poul Erik; Brock, Birgitte; Brock, Christina

doi:10.1177/2050640620925968

Cited by 14 publications

(11 citation statements)

References 35 publications

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“…In one study, osmotic diarrhea occurred 8 h after infusion of GLP-1 peptide (47), and GLP-1RAs have been shown to reduce intestinal uptake of glucose and lipids (48,49). Also, in patients with type 1 diabetes, liraglutide reduced colon transit time (50). So, hypothetically, semaglutide could induce diarrhea by altering nutrient absorption or intestinal motility.…”

Section: Gastrointestinal (Gi) Adverse Effectsmentioning

confidence: 99%

Safety of Semaglutide

2021

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The glucagon-like peptide-1 receptor agonist (GLP-1RA) semaglutide is the most recently approved agent of this drug class, and the only GLP-1RA currently available as both subcutaneous and oral formulation. While GLP-1RAs effectively improve glycemic control and cause weight loss, potential safety concerns have arisen over the years. For semaglutide, such concerns have been addressed in the extensive phase 3 registration trials including cardiovascular outcome trials for both subcutaneous (SUSTAIN: Semaglutide Unabated Sustainability in Treatment of Type 2 Diabetes) and oral (PIONEER: Peptide InnOvatioN for the Early diabEtes tReatment) semaglutide and are being studied in further trials and registries, including real world data studies. In the current review we discuss the occurrence of adverse events associated with semaglutide focusing on hypoglycemia, gastrointestinal side effects, pancreatic safety (pancreatitis and pancreatic cancer), thyroid cancer, gallbladder events, cardiovascular aspects, acute kidney injury, diabetic retinopathy (DRP) complications and injection-site and allergic reactions and where available, we highlight potential underlying mechanisms. Furthermore, we discuss whether effects are specific for semaglutide or a class effect. We conclude that semaglutide induces mostly mild-to-moderate and transient gastrointestinal disturbances and increases the risk of biliary disease (cholelithiasis). No unexpected safety issues have arisen to date, and the established safety profile for semaglutide is similar to that of other GLP-1RAs where definitive conclusions for pancreatic and thyroid cancer cannot be drawn at this point due to low incidence of these conditions. Due to its potent glucose-lowering effect, patients at risk for deterioration of existing DRP should be carefully monitored if treated with semaglutide, particularly if also treated with insulin. Given the beneficial metabolic and cardiovascular actions of semaglutide, and the low risk for severe adverse events, semaglutide has an overall favorable risk/benefit profile for patient with type 2 diabetes.

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Section: Gastrointestinal (Gi) Adverse Effectsmentioning

confidence: 99%

Safety of Semaglutide

2021

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“…In contrast, the impact of GLP-1 on colonic motility was opposite compared with other intestinal segments. A recent randomized and placebo-controlled trial confirmed that liraglutide could accelerate large bowel transit and decreases the motility index in type 1 diabetes and polyneuropathy, which may indicate better coordination of propulsive motility ( Wegeberg et al, 2020 ). Endogenous GLP-1 has a modest effect on gastric emptying.…”

Section: Discussionmentioning

confidence: 99%

“…Besides the well-known hypoglycemic effect of GLP-1 RAs, increasing evidence showed that GLP-1 RAs also profoundly affect the gastrointestinal motor system ( Marathe et al, 2011 ). In contrast, the impact of GLP-1 RAs on gut motility may vary with the change in intestinal segments ( Nauck et al, 1997 ; Thazhath et al, 2016 ; Wegeberg et al, 2020 ). Endogenous GLP-1 is rapidly degraded by the dipeptidyl peptidase-4 (DPP-4), resulting in a short half-life.…”

Section: Introductionmentioning

confidence: 99%

Impact of glucagon-like peptide 1 receptor agonist liraglutide and dipeptidyl peptidase-4 inhibitor sitagliptin on bowel cleaning and gastrointestinal symptoms in type 2 diabetes

et al. 2023

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Objective: Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) and dipeptidyl peptidase-4 inhibitors (DPP-4i) profoundly affect the gastrointestinal motor system, which may increase the incidence of inadequate bowel cleaning and gastrointestinal symptoms. Hence, this observational study mainly aimed to assess the influence of GLP-1 RAs liraglutide and DPP-4i sitagliptin on bowel preparation in type 2 diabetes (T2DM).Method: This observational study consecutively enrolled T2DM scheduled for a colonoscopy. Participants were prospectively separated into the liraglutide group (n = 120), sitagliptin group (n = 120), and control group (n = 120) based on the current hypoglycemic regimen. 3L split-dose polyethylene glycol regimens were used for bowel preparation. Experienced gastrointestinal endoscopists conducted colonoscopies. Lawrance Bowel-Preparation Tolerability Questionnaire and Boston Bowel Preparation Scale (BBPS) were conducted to assess bowel cleaning quality, tolerability, and safety.Results: The incidence of inadequate bowel cleaning was 17.5% in the liraglutide group, 20.5% in the sitagliptin group, and 21.7% in the control group. The difference among the three groups was not statistically significant (p = 0.927). Meanwhile, there were no significant differences in the mean BBPS, cecal intubation time, and polyp-detecting rates among the three groups (all p > 0.0.05). Nausea, vomiting, and bloating scores were increased in the liraglutide group compared with the other two groups (p < 0.05), whereas most were mild or very mild. Subgroup analyses showed that the incidence of inadequate bowel cleaning in T2DM with diabetic peripheral neuropathy (DPN) was increased in the liraglutide group compared with the sitagliptin group (61.3% vs. 32.1%, p = 0.022) and control group (61.3% vs. 32.8%, p = 0.025).Conclusion: GLP-1RA liraglutide or DPP-4i sitagliptin did not significantly increase the incidence of inadequate bowel cleaning and gastrointestinal symptoms during bowel preparation. Liraglutide may increase the incidence of inadequate bowel preparation in patients with DPN. This study reveal that more attention and aggressive bowel preparation regimens should be given to the T2DM with DPN.Clinical Trial Registration: (https://www.chictr.org.cn/index.aspx), identifier (ChiCTR2200056148).

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“…This is the case of liraglutide, a glucagon-like peptide-1 receptor agonist, which is employed to reduce hyperglycemia and to control food intake [ 113 ]. Liraglutide has been indeed recently reported, other than to ameliorate the function of the ENS, leading to the normalization of colonic function in people with type 1 diabetes [ 114 ], to improve NOS activity and increase NO production [ 115 ].…”

Section: No and Possible Therapeutic Strategiesmentioning

confidence: 99%

Nitric Oxide: From Gastric Motility to Gastric Dysmotility

Idrizaj

Traini

Vannucchi

et al. 2021

IJMS

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It is known that nitric oxide (NO) plays a key physiological role in the control of gastrointestinal (GI) motor phenomena. In this respect, NO is considered as the main non-adrenergic, non-cholinergic (NANC) inhibitory neurotransmitter responsible for smooth muscle relaxation. Moreover, many substances (including hormones) have been reported to modulate NO production leading to changes in motor responses, further underlying the importance of this molecule in the control of GI motility. An impaired NO production/release has indeed been reported to be implicated in some GI dysmotility. In this article we wanted to focus on the influence of NO on gastric motility by summarizing knowledge regarding its role in both physiological and pathological conditions. The main role of NO on regulating gastric smooth muscle motor responses, with particular reference to NO synthases expression and signaling pathways, is discussed. A deeper knowledge of nitrergic mechanisms is important for a better understanding of their involvement in gastric pathophysiological conditions of hypo- or hyper-motility states and for future therapeutic approaches. A possible role of substances which, by interfering with NO production, could prove useful in managing such motor disorders has been advanced.

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Liraglutide accelerates colonic transit in people with type 1 diabetes and polyneuropathy: A randomised, double‐blind, placebo‐controlled trial

Cited by 14 publications

References 35 publications

Safety of Semaglutide

Safety of Semaglutide

Impact of glucagon-like peptide 1 receptor agonist liraglutide and dipeptidyl peptidase-4 inhibitor sitagliptin on bowel cleaning and gastrointestinal symptoms in type 2 diabetes

Nitric Oxide: From Gastric Motility to Gastric Dysmotility

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