The purpose of this study is to evaluate how well brenipatide (LY3537031) is tolerated, what side effects may occur, and the safety and efficacy in participants with Irritable Bowel Syndrome-Diarrhea (IBS-D). The study drug will be administered subcutaneously (SC) (under the skin) when compared with placebo.

The study will last approximately 35 weeks.

Inclusion Criteria:

• Meet Rome IV criteria for IBS-D, which includes having greater than 25% of bowel movements with Bristol Stool Form Scale (BSFS) Types 6 or 7 and <25% of bowel movements with BSFS Types 1 or 2

• Based on the daily eDiary collection during the screening period:

  • Have average of worst abdominal pain score of ≥3.0 on a 0-to-10-point scale during the 14 consecutive days prior to randomization
  • Have at least 4 days per week with a maximum BSFS ≥5 AND with at least 2 days of the 4 days per week with a maximum BSFS ≥6 during the 14 consecutive days prior to randomization

• Have had no major changes in diet in the 4 weeks prior to screening

Exclusion Criteria:

• Have a diagnosis of IBS with a subtype of constipation, mixed IBS, or unclassified IBS by the Rome IV criteria
• Have a history of inflammatory or immune-mediated gastrointestinal disorders
• Have a known clinically significant gastric emptying abnormality

Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.

Data are available 6 months after the primary publication or approval of the indication studied in the US and European Union (EU), whichever is later. Data will be indefinitely available for requesting.

A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.