glucagon-like-peptide-1 and Pain

Glucagon-like peptide-1 receptor agonist ROSE-010 has been studied for management of irritable bowel syndrome (IBS). ROSE-010 showed promising effects by reducing pain during attacks of IBS. In this exploratory substudy, we cross-analyzed earlier data to identify the most suitable subpopulation for treatment with ROSE-010.. Data comprising 166 participants (116 females, 50 males) treated by subcutaneous injection with ROSE-010 at 100 µg and 300 µg versus placebo were broken down into subpopulations with recall of historical pain intensity, pain intensity immediately before treatment, gender, age, BMI, IBS subtype as well as pain intensity and pain relief of ROSE-010 with relationship to plasma glucose using visual analogue scores. Statistical cross-analysis was performed to detect optimal responders for adequate pain relief response.. ROSE-010 gave dose- and time-dependent effects with maximum pain relief at 300 µg relative 100 µg and placebo at 120 min post injection. Females had greater pain relief than males; age and BMI did not affect treatment response. IBS pain relief was greatest in constipation-dominant IBS (IBS-C) and mixed IBS (IBS-M) relative diarrhea-dominant and unspecified IBS.. Clinical trial data indicate that female participants are more likely than males to respond to ROSE-010 100 µg and 300 µg to achieve meaningful IBS pain relief. Maximum pain relief was achieved at 120 min with the higher dose, although this was accompanied with higher rates of nausea. Improvement of IBS pain attacks was most pronounced in IBS-C and IBS-M, suggesting these subgroups to be optimal ROSE-010 responders.

Topics: Constipation; Diarrhea; Female; Glucagon-Like Peptide 1; Glucagon-Like Peptide-1 Receptor; Humans; Irritable Bowel Syndrome; Male; Pain; Pain Measurement; Peptide Fragments; Treatment Outcome

There is currently no treatment available to manage acute pain attacks in IBS patients regardless of subtype.. To evaluate efficacy and safety of the GLP-1 analogue ROSE-010 in patients with irritable bowel syndrome (IBS) through a randomized, double-blind, placebo-controlled study.. Eligible patients (n = 166) meeting Rome II criteria were randomly assigned to receive single subcutaneous injections of ROSE-010 100 microg, 300 microg and placebo in a cross-over design. Safety was assessed from spontaneously reported adverse events and measurement of vital signs. Patient-rated pain relief and intensity were measured on a 100-mm visual analogue scale. The primary efficacy variable was proportion of patients with >50% maximum total pain relief response from 10 to 60 min after treatment. Secondary endpoints included the maximum summed pain intensity difference, time to meaningful pain relief and patient ratings of satisfaction with treatment.. Twice as many patients were responders in the primary efficacy endpoint after both ROSE-010 injections compared to placebo (24%P = 0.011, 23%P = 0.005, and 12% after 300 microg, 100 microg and placebo injections, respectively). Similar results were obtained for the proportion of patients with total pain intensity response. Times to meaningful and total pain relief were shorter for both doses of ROSE-010 compared with placebo. Compared with placebo, more patients (P < 0.05) were satisfied with ROSE-010 and considered ROSE-010 better than previous IBS medications used.. ROSE-010 was well tolerated and provided fast and effective relief of acute pain attacks on demand in IBS patients.

Topics: Adult; Double-Blind Method; Female; Glucagon-Like Peptide 1; Humans; Infusions, Subcutaneous; Irritable Bowel Syndrome; Male; Middle Aged; Pain; Pain Measurement; Treatment Outcome

To prospectively characterize changes in body weight, satiety, and postprandial gut hormone profiles following esophagectomy.. With improved oncologic outcomes in esophageal cancer, there is an increasing focus on functional status and health-related quality of life in survivorship. Early satiety and weight loss are common after esophagectomy, but the pathophysiology of these phenomena remains poorly understood.. In this prospective study, consecutive patients undergoing esophagectomy with gastric conduit reconstruction were studied preoperatively and at 10 days, 6 weeks, and 3 months postoperatively. Glucagon-like peptide 1 (GLP-1) immunoreactivity of plasma collected immediately before and at 15, 30, 60, 90, 120, 150, and 180 minutes after a standardized 400-kcal mixed meal was determined. Gastrointestinal symptom scores were computed using European Organization for Research and Treatment of Cancer questionnaires.. Body weight loss at 6 weeks and 3 months postoperatively among 13 patients undergoing esophagectomy was 11.1 ± 2.3% (P < 0.001) and 16.3 ± 2.2% (P < 0.0001), respectively. Early satiety (P = 0.043), gastrointestinal pain and discomfort (P = 0.01), altered taste (P= 0.006), and diarrhea (P= 0.038) scores increased at 3 months postoperatively. Area under the curve for the satiety gut hormone GLP-1 was significantly increased from 10 days postoperatively (2.4 ± 0.2-fold increase, P < 0.01), and GLP-1 peak increased 3.8 ± 0.6-, 4.7 ± 0.8-, and 4.4 ± 0.5-fold at 10 days, 6 weeks, and 3 months postoperatively (all P < 0.0001). Three months postoperatively, GLP-1 area under the curve was associated with early satiety (P = 0.0002, R = 0.74), eating symptoms (P = 0.007, R = 0.54), and trouble enjoying meals (P = 0.0004, R = 0.73).. After esophagectomy, patients demonstrate an exaggerated postprandial satiety gut hormone response, which may mediate postoperative changes in satiety, body weight, and gastrointestinal quality of life.

Topics: Aged; Blood Glucose; Esophageal Neoplasms; Esophagectomy; Female; Gastrointestinal Diseases; Glucagon-Like Peptide 1; Humans; Insulin; Male; Middle Aged; Pain; Postoperative Complications; Postprandial Period; Prospective Studies; Quality of Life; Satiety Response; Taste Disorders; Treatment Outcome; Weight Loss