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

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).

[1]  Wei Yang,et al.  GLP−1 receptor agonists for the treatment of obesity: Role as a promising approach , 2023, Frontiers in Endocrinology.

[2]  C. Rayner,et al.  Normal and disordered gastric emptying in diabetes: recent insights into (patho)physiology, management and impact on glycaemic control , 2022, Diabetologia.

[3]  C. Rayner,et al.  Prevalence of Gastrointestinal Symptoms in Chinese Community-Dwelling Adults with and without Diabetes. , 2022, Nutrients.

[4]  K. Ogurtsova,et al.  IDF Diabetes Atlas: Global estimates of undiagnosed diabetes in adults for 2021 , 2021, Diabetes Research and Clinical Practice.

[5]  Linh H. Lieu,et al.  Time and metabolic state-dependent effects of GLP-1R agonists on NPY/AgRP and POMC neuronal activity in vivo , 2021, Molecular metabolism.

[6]  C. Deacon Dipeptidyl peptidase 4 inhibitors in the treatment of type 2 diabetes mellitus , 2020, Nature Reviews Endocrinology.

[7]  A. Farmer,et al.  Liraglutide accelerates colonic transit in people with type 1 diabetes and polyneuropathy: A randomised, double-blind, placebo-controlled trial , 2020, United European gastroenterology journal.

[8]  S. Selbuz,et al.  Gastrointestinal symptoms in pediatric patients with type 1 diabetes mellitus , 2019, Journal of pediatric endocrinology & metabolism : JPEM.

[9]  Yasushi Tanaka,et al.  Effects of anagliptin on plasma glucagon levels and gastric emptying in patients with type 2 diabetes: an exploratory randomized controlled trial versus metformin. , 2019, Diabetes research and clinical practice.

[10]  D. Drucker Mechanisms of Action and Therapeutic Application of Glucagon-like Peptide-1. , 2018, Cell metabolism.

[11]  Y. Aso,et al.  Effect of GLP-1 receptor agonist on gastrointestinal tract motility and residue rates as evaluated by capsule endoscopy. , 2017, Diabetes & metabolism.

[12]  C. Daskalakis,et al.  Patient Characteristics Associated With Quality of Colonoscopy Preparation: A Systematic Review and Meta‐analysis , 2017, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[13]  Carmen V. Villabona,et al.  Evaluation of the effect of GLP‐1 agonists on quality of bowel preparation for colonoscopy in patients with diabetes , 2017 .

[14]  M. Kahle,et al.  Occurrence of nausea, vomiting and diarrhoea reported as adverse events in clinical trials studying glucagon‐like peptide‐1 receptor agonists: A systematic analysis of published clinical trials , 2017, Diabetes, obesity & metabolism.

[15]  A. Farmer,et al.  Type 1 diabetic patients with peripheral neuropathy have pan-enteric prolongation of gastrointestinal transit times and an altered caecal pH profile , 2017, Diabetologia.

[16]  S. Choi,et al.  Inadequate Bowel Cleansing Efficacy of Split-dose Polyethylene Glycol for Colonoscopy in Type 2 Diabetic Patients: A Prospective and Blinded Study , 2016, Journal of clinical gastroenterology.

[17]  D. Cahen,et al.  Gastrointestinal actions of glucagon‐like peptide‐1‐based therapies: glycaemic control beyond the pancreas , 2016, Diabetes, obesity & metabolism.

[18]  Karen L Jones,et al.  The Glucagon-Like Peptide 1 Receptor Agonist Exenatide Inhibits Small Intestinal Motility, Flow, Transit, and Absorption of Glucose in Healthy Subjects and Patients With Type 2 Diabetes: A Randomized Controlled Trial , 2015, Diabetes.

[19]  P. Kempler,et al.  Diabetes-Related Dysfunction of the Small Intestine and the Colon: Focus on Motility , 2015, Current Diabetes Reports.

[20]  Minhu Chen,et al.  3-L Split-dose is Superior to 2-L Polyethylene Glycol in Bowel Cleansing in Chinese Population , 2015, Medicine.

[21]  J. Holst,et al.  The impact of dipeptidyl peptidase 4 inhibition on incretin effect, glucose tolerance, and gastrointestinal-mediated glucose disposal in healthy subjects. , 2014, European journal of endocrinology.

[22]  I. Lawrance,et al.  A Validated Bowel-Preparation Tolerability Questionnaire and Assessment of Three Commonly Used Bowel-Cleansing Agents , 2013, Digestive Diseases and Sciences.

[23]  B. Enestvedt,et al.  4-Liter split-dose polyethylene glycol is superior to other bowel preparations, based on systematic review and meta-analysis. , 2012, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[24]  C. Kapitza,et al.  Effect of the once-daily human GLP-1 analogue liraglutide on appetite, energy intake, energy expenditure and gastric emptying in type 2 diabetes. , 2012, Diabetes research and clinical practice.

[25]  J. Jelsing,et al.  Liraglutide: short‐lived effect on gastric emptying—long lasting effects on body weight , 2012, Diabetes, obesity & metabolism.

[26]  M. Horowitz,et al.  Effects of GLP-1 and Incretin-Based Therapies on Gastrointestinal Motor Function , 2011, Experimental diabetes research.

[27]  F. Clavel-Chapelon,et al.  Metabolic Syndrome and Risks of Colon and Rectal Cancer: The European Prospective Investigation into Cancer and Nutrition Study , 2011, Cancer Prevention Research.

[28]  K. H. Park,et al.  Patient Factors Predictive of Inadequate Bowel Preparation Using Polyethylene Glycol: A Prospective Study in Korea , 2009, Journal of clinical gastroenterology.

[29]  B. Jacobson,et al.  Comprehensive validation of the Boston Bowel Preparation Scale. , 2009, Gastrointestinal endoscopy.

[30]  R. DeFronzo,et al.  Effects of exenatide versus sitagliptin on postprandial glucose, insulin and glucagon secretion, gastric emptying, and caloric intake: a randomized, cross-over study , 2008, Current medical research and opinion.

[31]  Michael Camilleri,et al.  Effects of Dipeptidyl Peptidase-4 Inhibition on Gastrointestinal Function, Meal Appearance, and Glucose Metabolism in Type 2 Diabetes , 2007, Diabetes.

[32]  A. Sanabria,et al.  Randomized controlled trial. , 2005, World journal of surgery.

[33]  J. Holst,et al.  Glucagon-like peptide 1 inhibition of gastric emptying outweighs its insulinotropic effects in healthy humans. , 1997, American journal of physiology. Endocrinology and metabolism.

[34]  [Chinese guideline for bowel preparation for colonoscopy (2019, Shanghai)]. , 2019 .