Lubiprostone improves bowel movements in patients with diabetes

Last Updated: 2016-12-21

By Lorraine L. Janeczko

NEW YORK (Reuters Health) - Lubiprostone is a safe and effective treatment for chronic constipation in diabetics, new research reports.

Lubiprostone can increase weekly spontaneous bowel movements (SBMs) and decrease colonic transit time (CTT) in patients with diabetes mellitus and chronic idiopathic constipation, the authors reported in American Journal of Gastroenterology, online December 6.

"Using a pH motility capsule, we were able to objectively demonstrate that lubiprostone significantly reduced CTT in our cohort of diabetic patients suffering with constipation - the most common gastrointestinal (GI) complication in diabetic patients - compared to placebo. We also found that the average number of weekly SBMs increased significantly from baseline in the lubiprostone group compared to the placebo group," lead author Dr. Jennifer Christie told Reuters Health in an email.

"Given that the prevalence of diabetes is increasing dramatically in the U.S. population, proven medications to treat the GI complications of diabetes are greatly needed. These findings may impact patient care in that more health care providers may recognize that constipation is a common GI compliant in diabetic patients and may consider lubiprostone a safe and effective therapy in this group," added Dr. Christie, associate professor of medicine and director of gastrointestinal motility and clinical research in the Division of Digestive Diseases at Emory School of Medicine in Atlanta, Georgia.

Dr. Christie and her colleagues recruited diabetic patients with chronic idiopathic constipation from outpatient clinics at two academic medical centers. The participants were 56.9 years of age on average and both groups had similar demographics and baseline data.

In the double-blind randomized controlled trial, 37 patients received 48 mcg lubiprostone daily and 39 were given placebo for 8 weeks. The researchers used a wireless motility capsule (SmartPill, Buffalo, New York) to evaluate CTT.

The primary end point was the difference in the number of SBMs per week compared with baseline for each group at each week after the therapy was started. Secondary end points included changes in CTT after 4 weeks of therapy, the Patient Assessment of Constipation Quality of Life (PAC-QOL) after 8 weeks of therapy, changes from baseline in associated gastrointestinal symptoms, and the need for rescue medication at 2, 4, and 8 weeks.

Over 8 weeks, patients in the lubiprostone group averaged 1.83 (P=0.02) more weekly SBMs than those in the placebo group, compared with baseline. At Week 4, compared with baseline, CTT in the lubiprostone group had decreased 13 hours on average, while in the placebo group it increased 7 hours on average, leading to a treatment effect of around 20 hours (P=0.006).

PAC-QOL improved in both groups but the difference between the groups was not significant. No difference was found in associated GI symptoms and the need for rescue medication between the two groups after 8 weeks, and no serious adverse events were reported during the study.

Dr. Christie said in an email that strengths of the study include its design, its focus on diabetic patients, and its inclusion of subjective and objective patient-related outcomes. Limitations include its moderate sample size and high pre-randomization dropout rate. However, she noted, only 11% of the randomized patients dropped out of the study and the attrition rates in both groups were similar, indicating that the internal between-group comparisons are valid.

Dr. Daniela Jodorkovsky, director of neurogastroenterology and motility in the Division of Digestive and Liver Diseases at Columbia University Medical Center in New York City, said in an email, "Lubiprostone is currently approved for chronic idiopathic constipation, irritable bowel syndrome with constipation, and opioid-induced constipation. However, it has not exclusively been studied in diabetics, who can have troubling constipation symptoms."

"What is interesting about this study is the authors' attempt to determine the physiologic explanation for this effect using wireless motility capsules to measure colon transit time," said Dr. Jodorkovsky, who was not involved in the study.

"One caveat about this study," she offered, "is that, despite improving bowel movement frequency, overall quality-of-life symptoms did not differ between the lubiprostone and placebo groups, which leaves us to continue to wonder how to best address those important issues."

Dr. Stephanie A. McAbee, assistant professor of medicine in the Division of Gastroenterology at Vanderbilt University Medical Center in Nashville, Tennessee, noted in an email that this is the first study to show that lubiprostone is effective specifically for chronic constipation in diabetics.

"Although the population is relatively small, the study suggests that a well-known standard treatment for idiopathic constipation and irritable bowel syndrome with constipation may effectively treat constipation in diabetics as well," said Dr. McAbee, who also was not involved in the study.

"Interestingly, while colon transit times and the number of weekly bowel movements improved in the treatment arm, associated GI symptom and quality-of-life scores were not significantly greater over placebo, although this may be due to the relatively small sample size," she added.

The authors recommend further study to explore which diabetic patients are most likely to respond to lubiprostone.

This work was funded by Takeda International Pharmaceuticals.

SOURCE: http://bit.ly/2hU9E5K

Am J Gastroenterol 2016.