The Effect of Probiotics on GLP-1 Receptor Agonist Therapy in Patients With Obesity: A Randomized, Double-Blind, Controlled Trial
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 102
- 试验地点
- 3
- 主要终点
- Cumulative incidence proportion of gastrointestinal adverse events during semaglutide treatment
研究概览
简要总结
This randomized, double-blind, placebo-controlled trial evaluated the effects of a four-strain probiotic formulation in adults with obesity receiving semaglutide. Participants received either the probiotic formulation or placebo, beginning two The primary objective was to determine whether probiotic supplementation reduced gastrointestinal adverse events associated with semaglutide treatment. The primary outcome comprised two complementary measures during the 12-week semaglutide treatment period: the proportion of participants reporting at least one protocol-defined gastrointestinal adverse event and the proportion of treatment days on which a participant reported at least one protocol-defined gastrointestinal adverse event in the daily diary. Secondary outcomes included gastrointestinal symptom severity and duration, non-gastrointestinal adverse events, health-related quality of life, body weight reduction, treatment discontinuation, and inability to escalate the semaglutide dose as planned.weeks before semaglutide initiation and continuing throughout the 12-week semaglutide-treatment and dose-escalation period.
详细描述
Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), including semaglutide, are effective pharmacological treatments for obesity. Semaglutide acts through multiple mechanisms, including enhancement of satiety, reduction of appetite, slowing of gastric emptying, stimulation of glucose-dependent insulin secretion, and suppression of glucagon secretion. Clinical studies have demonstrated that semaglutide can produce clinically meaningful body weight reduction and improve glycemic and other cardiometabolic outcomes. However, treatment is frequently associated with gastrointestinal adverse events (GI-AEs), particularly during dose escalation. Commonly reported GI-AEs include nausea, vomiting, diarrhea, constipation, abdominal pain, and flatulence.
The gut microbiota may influence gastrointestinal function, intestinal barrier integrity, host metabolism, and inflammatory processes. Selected probiotic strains may therefore have the potential to support gastrointestinal function and improve treatment tolerability. This provided the rationale for evaluating a specifically selected probiotic formulation as a supportive intervention in adults with obesity receiving semaglutide.
This was a randomized, double-blind, placebo-controlled, parallel-group interventional trial conducted in adults with obesity. Participants were randomly assigned to receive either a four-strain probiotic formulation or a matching placebo. The probiotic formulation contained Bifidobacterium animalis subsp. lactis AZHx1, Limosilactobacillus reuteri AZHx2, Lacticaseibacillus casei AZHx3, and Lacticaseibacillus rhamnosus AZHx4.
The assigned probiotic or placebo was initiated two weeks before the first dose of semaglutide and continued throughout the subsequent 12-week semaglutide-treatment period. Semaglutide was administered once weekly according to a stepwise dose-escalation schedule: 0.25 mg during weeks 1-4, 0.5 mg during weeks 5-8, and 1.0 mg during weeks 9-12.
Gastrointestinal tolerability was assessed using two complementary sources of information: investigator assessments performed at scheduled study visits and prospective daily symptom reporting by participants using diaries. Four scheduled study visits covered semaglutide initiation and the subsequent dose-escalation and treatment period, while participant diaries provided daily observations throughout the 12 weeks of semaglutide treatment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Supportive Care
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •BMI ≥ 30 kg/m² without T2DM or with coexisting T2DM;
- •patients starting GLP-1RA treatment;
- •provided written informed consent;
- •patients with ability to adhere to the investigators' instructions regarding study protocol and procedures.
排除标准
- •patients with gastrointestinal conditions unrelated to GLP-1RA therapy,
- •known food allergies and lactose intolerance,
- •severe neurological conditions, malignancy, and hepatic or renal impairment,
- •pregnancy or breastfeeding,
- •anemia and leukocytosis in laboratory tests,
- •the use of intestine microbiota-targeted dietary supplements or drugs (i.e. probiotics, prebiotics, synbiotics, or postbiotics including butyric acid) within the last 3 months,
- •the use of antibiotics within the last 1 month,
- •the use of the following drugs: insulin, glucocorticosteroids, proton pump blockers,
- •a surgical procedure scheduled during the clinical study,
- •being enrolled in another clinical trial within the last 3 months,
- •alcohol or substance abuse.
研究组 & 干预措施
Probiotic
Participants assigned to this arm received the probiotic formulation in addition to semaglutide treatment.
干预措施: Four-strain probiotic formulation (Dietary Supplement)
Placebo
Participants assigned to this arm received a matching placebo containing maltodextrin in addition to semaglutide treatment.
干预措施: Maltodextrin (Placebo) (Dietary Supplement)
结局指标
主要结局
Cumulative incidence proportion of gastrointestinal adverse events during semaglutide treatment
时间窗: During the 12-week semaglutide treatment and dose-escalation period
.The cumulative incidence proportion of gastrointestinal adverse events (GI-AEs) was defined as the percentage of participants who experienced at least one protocol-defined GI-AE during the 12-week semaglutide treatment and dose-escalation period. GI-AEs included nausea, vomiting, diarrhea, constipation, abdominal pain, and flatulence and were assessed by investigators at monthly study visits. Cumulative incidence was calculated for any GI-AE and separately for each individual GI-AE as the number of participants experiencing the respective event at least once during the 12-week period divided by the number of participants assessed, multiplied by 100. A participant experiencing the same GI-AE at more than one visit was counted only once for that GI-AE. The possible range was 0%-100%, with higher values indicating a higher cumulative incidence.
Prevalence of gastrointestinal adverse events during semaglutide treatment
时间窗: During the 12-week semaglutide treatment and dose-escalation period
GI-AE prevalence was defined as the percentage of days during the 12-week semaglutide treatment period on which a participant reported at least one protocol-defined gastrointestinal adverse event (GI-AE) in the daily diary. Protocol-defined GI-AEs included nausea, vomiting, diarrhea, constipation, abdominal pain, and flatulence. A day on which more than one GI-AE was reported was counted only once for the overall GI-AE prevalence. For each participant, prevalence was calculated as the number of days with at least one GI-AE divided by the 84 planned semaglutide-treatment days, multiplied by 100. Group results were summarized as the mean participant-level GI-AE prevalence. The possible range was 0%-100%, with higher values indicating a greater proportion of treatment days affected by GI-AEs.
次要结局
- Change in Health-Related Quality of Life (SF-36v2)(Baseline (before initiation of semaglutide treatment) and Week 12 (end of semaglutide treatment))
- Severity of Selected Gastrointestinal Adverse Events (GI-AEs)(From initiation of semaglutide treatment through Week 12)
- Number of Days With Individual Gastrointestinal Symptoms(From initiation of semaglutide treatment through Week 12)
- Change in Body Weight During Semaglutide Treatment(Baseline (before initiation of semaglutide treatment) and during scheduled study visits through Week 12)
- Number of Participants Who Discontinued Semaglutide Treatment(From initiation of semaglutide treatment through Week 12)
- Number of Participants Unable to Escalate Semaglutide Dose According to the Planned Schedule(From initiation of semaglutide treatment through Week 12)