Article
Gastroenterology & Hepatology
William D. Chey, Gregory S. Sayuk, Wilmin Bartolini, David S. Reasner, Susan M. Fox, Wieslaw Bochenek, Ramesh Boinpally, Elizabeth Shea, Kenneth Tripp, Niels Borgstein
Summary: The study demonstrates that the delayed-release formulation of linaclotide and MD-7246 show better improvement in abdominal pain compared to placebo. MD-7246 shows sustained but modest effects on pain relief, suggesting further investigation as a novel treatment for abdominal pain.
AMERICAN JOURNAL OF GASTROENTEROLOGY
(2021)
Article
Gastroenterology & Hepatology
Lin Chang, Brian E. Lacy, Baha Moshiree, Amy Kassebaum, Jessica L. Abel, Jennifer Hanlon, Wilmin Bartolini, Ramesh Boinpally, Wieslaw Bochenek, Susan M. Fox, Madhuja Mallick, Ken Tripp, Nicholas Omniewski, Elizabeth Shea, Niels Borgstein
Summary: Linaclotide significantly improved abdominal symptoms related to constipation-predominant irritable bowel syndrome (IBS-C) compared to placebo, including bloating, discomfort, and pain. The study found that linaclotide had a higher overall change from baseline in abdominal score (AS) and a higher responder rate for abdominal symptoms improvement, with diarrhea being the most common side effect. The use of a novel multi-item AS derived from the Diary for IBS Symptoms-Constipation may be valuable in future clinical studies for IBS-C to measure meaningful improvements beyond traditional endpoints.
AMERICAN JOURNAL OF GASTROENTEROLOGY
(2021)
Article
Chemistry, Medicinal
Nayara Braga Emidio, Hue N. T. Tran, Asa Andersson, Philip E. Dawson, Fernando Albericio, Irina Vetter, Markus Muttenthaler
Summary: The high susceptibility to proteolytic degradation in the gastrointestinal tract limits the therapeutic application of peptide drugs, such as linaclotide, for gastrointestinal disorders. Improvements in gastrointestinal stability through strategic modifications of linaclotide analogues can significantly enhance their therapeutic efficacy and create potential for the development of the next generation of orally administered peptide drugs for gastrointestinal disorders.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Review
Oncology
Moein Piroozkhah, Ali Aghajani, Pooya Jalali, Arvin Shahmoradi, Mobin Piroozkhah, Younes Tadlili, Zahra Salehi
Summary: This systematic review focuses on the latest research on the guanylate cyclase-C (GC-C) signaling axis in colorectal cancer (CRC). The findings reveal that alterations in GC-C signaling compartments in CRC tissue have potential as diagnostic, prognostic, and therapeutic markers. Moreover, the GC-C signaling axis may be a promising target for treating CRC.
FRONTIERS IN ONCOLOGY
(2023)
Article
Endocrinology & Metabolism
Aaron Otero, Sara Becerril, Marina Martin, Javier A. Cienfuegos, Victor Valenti, Rafael Moncada, Victoria Catalan, Javier Gomez-Ambrosi, Maria A. Burrell, Amaia Rodriguez, Gema Fruhbeck
Summary: Obesity leads to fat deposition in non-adipose organs, including the pancreas, which is associated with inflammation and beta-cell dysfunction. This study aimed to investigate the mechanisms behind the improvement of pancreas fat accumulation after bariatric surgery. It was found that sleeve gastrectomy reduced pancreas steatosis and inflammation, and upregulated GUCA2A and GUCY2C in the pancreas, which might contribute to the beneficial effects of bariatric surgery. Additionally, guanylin and uroguanylin were found to alleviate lipotoxicity in beta-cells and modulate insulin synthesis and release.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Gastroenterology & Hepatology
Li Hua Peng, Jing Yuan Fang, Ning Dai, Xi Zhong Shen, You Lin Yang, Jing Sun, Yun Sheng Yang
Summary: Linaclotide (290 μg/d) was effective and well-tolerated in Chinese IBS-C patients, with a rapid onset of action.
JOURNAL OF DIGESTIVE DISEASES
(2022)
Article
Gastroenterology & Hepatology
Gregory S. Sayuk, Scott A. Waldman, Darren M. Brenner
Summary: This article summarizes the mechanisms of action of commonly used therapies for chronic idiopathic constipation and irritable bowel syndrome with constipation, explaining how these mechanisms contribute to the effectiveness and safety of each treatment option.
AMERICAN JOURNAL OF GASTROENTEROLOGY
(2022)
Article
Pharmacology & Pharmacy
Emily V. Wechsler, Eric D. Shah
Summary: A review summarized important determinants of choosing IBS treatment, including clinical profiles and cost-effectiveness of prescription drugs; the shared decision-making model helps guide informed discussions for patients to select the appropriate treatment.
Article
Medicine, Research & Experimental
Dunming Xiao, Yue Zhang, Wanxin Chen, Jianwei Xuan, Yingyao Chen
Summary: This study evaluated the cost-effectiveness of linaclotide for patients with IBS-C. The results showed that linaclotide treatment for 1 year can improve patients' QALYs at a lower cost compared to other medications. Therefore, linaclotide is highly cost-effective.
ADVANCES IN THERAPY
(2022)
Article
Medicine, General & Internal
Darren M. Brenner, Spencer Dorn, Ronald P. Fogel, Jennifer Christie, Adam P. Laitman, Jonathan Rosenberg
Summary: This integrated analysis demonstrates that plecanatide is safe and effective in treating symptoms of irritable bowel syndrome with constipation (IBS-C) in adult patients. Plecanatide significantly improved symptoms and had a greater overall and sustained response compared to placebo. The most common adverse event was diarrhea, but the incidence was low without study discontinuation.
INTERNATIONAL JOURNAL OF GENERAL MEDICINE
(2023)
Article
Medicine, General & Internal
Juan J. Sebastian Domingo
Summary: Irritable bowel syndrome is a common functional bowel disorder with significant impact on patients' daily lives and society's economy. It is characterized by abdominal pain, bloating, and altered bowel movements, and its etiology and pathophysiological mechanism are still unknown.
Article
Gastroenterology & Hepatology
Brooks D. Cash, Amol Sharma, Anna Walker, Adam P. Laitman, Lin Chang
Summary: This study aimed to evaluate the effectiveness of plecanatide in patients with chronic idiopathic constipation (CIC) or irritable bowel syndrome with constipation (IBS-C) with severe constipation. The results showed that plecanatide significantly improved the symptoms of severe constipation in both CIC and IBS-C patients.
NEUROGASTROENTEROLOGY AND MOTILITY
(2023)
Review
Pediatrics
Desiree F. Baaleman, Shivani Gupta, Marc A. Benninga, Neetu Bali, Karla H. Vaz, Desale Yacob, Carlo Di Lorenzo, Peter L. Lu
Summary: Linaclotide is well-tolerated and effective in treating functional constipation and IBS-C in adults, but its efficacy and safety in children remain unclear. A retrospective study of children at Nationwide Children's Hospital in Columbus, Ohio found that nearly half of children with FC or IBS-C benefited from linaclotide, but adverse events were relatively common. Further prospective, controlled studies are needed to confirm these findings and identify which patients are most likely to benefit from linaclotide.
Article
Gastroenterology & Hepatology
Alejandro Velez Lopez, Amanda Waddell, Simona Antonacci, Daniel Castillo, Neha Santucci, Nicholas J. Ollberding, Emily M. Eshleman, Lee A. Denson, Theresa Alenghat
Summary: This study demonstrated that microbiota-derived butyrate can dampen human colonic responses to linaclotide in patient-derived colonoids, providing support for the incorporation of microbiota and metabolomic assessment to improve precision medicine for DGBI patients.
NEUROGASTROENTEROLOGY AND MOTILITY
(2023)
Review
Gastroenterology & Hepatology
Alfred D. Nelson, Christopher J. Black, Lesley A. Houghton, Nahyr Sofia Lugo-Fagundo, Brian E. Lacy, Alexander C. Ford
Summary: In a study of IBS-C patients, it was found that all licensed drugs were more effective than a placebo for abdominal bloating, with linaclotide showing the highest efficacy in relieving this symptom. Further research is needed to understand the long-term efficacy and mechanisms of action of these treatments.
ALIMENTARY PHARMACOLOGY & THERAPEUTICS
(2021)