Treatment of bile acid diarrhea with GLP-1 receptor agonists: A Promising Yet Understudied Approach.

Bile acid diarrhea (BAD) is a chronic and socially debilitating disease characterized by abdominal pain, diarrhea, urgency, and fecal incontinence. Recently, in a six-week randomized controlled trial (RCT), we showed that the glucagon-like peptide 1 receptor agonist (GLP-1RA) liraglutide is superior to bile acid sequestration (considered standard-of-care) using colesevelam in reducing BAD symptoms. The emergence of new, more potent, and longer-acting GLP-1RAs has spurred an interest in these treatments in BAD management.

evoke and evoke+: design of two large-scale, double-blind, placebo-controlled, phase 3 studies evaluating efficacy, safety, and tolerability of semaglutide in early-stage symptomatic Alzheimer's disease.

Background: Disease-modifying therapies targeting the diverse pathophysiology of Alzheimer's disease (AD), including neuroinflammation, represent potentially important and novel approaches. The glucagon-like peptide-1 receptor agonist semaglutide is approved for the treatment of type 2 diabetes and obesity and has an established safety profile. Semaglutide may have a disease-modifying, neuroprotective effect in AD through multimodal mechanisms including neuroinflammatory, vascular, and other AD-related processes.

Pharmacokinetic/Pharmacodynamic Modeling of Efficacy and Hypoglycemia Rate When Switching From Once-Daily Basal Insulin to Once-Weekly Insulin Icodec Without or With a One-Time Additional Dose in Insulin-Experienced Individuals With Type 2 Diabetes.

Objective: Insulin icodec (icodec), a once-weekly basal insulin analog, has been investigated in the phase 3a ONWARDS clinical trial program. This pharmacokinetic (PK)/pharmacodynamic (PD) modeling analysis of data from the ONWARDS 2 and 4 trials investigated efficacy outcomes and hypoglycemia rate in insulin-experienced individuals with type 2 diabetes when switching from daily basal insulin to icodec without or with a 50% one-time additional dose for the first injection only.

Methods: Data from 2 randomized, 26-week, phase 3a trials of insulin-experienced individuals with type 2 diabetes on a basal (ONWARDS 2) or basal-bolus (ONWARDS 4) insulin regimen were used for PK/PD model development and validation.

Liraglutide and Colesevelam Change Serum and Fecal Bile Acid Levels in a Randomized Trial With Patients With Bile Acid Diarrhea.

Introduction: Both liraglutide and colesevelam improve bile acid diarrhea symptoms. Colesevelam binds excess amounts of diarrhea-causing bile acids in the colon, whereas the mode of action for liraglutide remains elusive. In this article, we examined the impact of colesevelam and liraglutide treatment on the concentrations of bile acids in serum and feces and the fecal microbiota composition to better understand the 2 drugs' modes of action.