Cambios en la composición Corporal Tras el Inicio de Agonistas Del Receptor de GLP-1 (GLP-1RA) en Adultos Con Obesidad o Diabetes Tipo 2: Cohorte Prospectiva multicéntrica en Vida Real
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 200
- 试验地点
- 2
- 主要终点
- Change in Appendicular Lean Mass
研究概览
简要总结
Researchers want to understand what happens to muscle and fat in the body after adults with obesity and/or type 2 diabetes start taking a GLP-1 receptor agonist medication (GLP-1RA), a type of drug already approved and commonly prescribed for weight loss and blood sugar control. This is not a drug trial. No experimental medication will be given. Instead, the study will follow people who are already starting this treatment or having their dose adjusted, as part of their regular medical care, and it will not change or interfere with any decision made by the participant's own doctor.
These medications help people lose weight, but not all weight loss is the same. Some of it can come from muscle instead of fat, and losing muscle can affect strength and daily function over time. This study will use a scan called DXA (dual energy X ray absorptiometry) to measure how much muscle and fat change over about one year, along with tests of grip strength, walking speed, and everyday physical performance.
About 168 adults will take part at two centers in Mexico: the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán in Mexico City and the Instituto de Diabetes, Obesidad y Nutrición in Cuernavaca. After an initial visit, participants will have a phone check-in at 12 weeks and follow-up visits at 24 and 52 weeks, including blood tests, body measurements, and short questionnaires about diet, physical activity, and muscle health. Some participants may also choose to give an extra blood sample for optional genetic testing; this is voluntary and does not affect participation in the main study.
There is no placebo, randomization, cost, or payment involved. All treatment decisions remain with the participant's own physician. By observing these changes under real world conditions, the study aims to help doctors better protect muscle while patients lose fat during treatment with these medications.
详细描述
Type 2 diabetes affects more than 500 million people worldwide, and in Mexico it affects about 17% of adults, often together with obesity, which affects around 37.1% of adults. This combination substantially increases the risk of cardiometabolic complications. GLP-1 receptor agonists (GLP-1RAs), also known as GLP-1 analogs or incretin mimetics, have changed the treatment of type 2 diabetes and obesity by producing clinically meaningful weight loss and improving metabolic outcomes. These medications mimic the body's incretin hormones, activating specific receptors that increase glucose-dependent insulin release and reduce glucagon release, helping control blood sugar. Their safety profile is well characterized. The most common side effects are gastrointestinal, mainly nausea, vomiting, and diarrhea, which tend to be dose dependent, occur mostly during dose titration, and are usually mild to moderate and temporary, though they are the main reason some people stop treatment.
Although these medications are effective for weight loss, most research so far has focused on total body weight rather than how different parts of the body change, particularly the balance between fat and muscle. This matters because the quality of weight loss, meaning how much comes from fat versus from muscle, can affect strength and physical function over time. The research question this study addresses is what the size and pattern of changes in body composition, specifically appendicular lean mass and fat mass measured by DXA, after adults with obesity and/or type 2 diabetes start a GLP-1 receptor agonist under real world clinical conditions. The working hypothesis is that after starting GLP-1RA therapy, participants will show longitudinal changes in body composition characterized by a reduction in fat mass along with a simultaneous decrease in appendicular lean mass, with different patterns of change across individuals, under real world conditions.
The main objective of the study is to evaluate the size and trajectory of changes in appendicular lean mass and fat mass, measured by DXA, over 12 months after starting or adjusting a GLP-1RA in adults with obesity and/or type 2 diabetes treated under real world conditions.
The study also has several secondary objectives. These include identifying patterns that link the loss of appendicular lean mass with the regain of body fat during follow-up; assessing changes in grip strength and how they relate to changes in appendicular muscle mass; and evaluating whether treatment adherence, dose reduction, or stopping treatment is associated with a higher likelihood of losing muscle mass or regaining fat. The study will also assess changes in physical performance and functional mobility, using usual walking speed and the Timed Up and Go test in adults, and the Short Physical Performance Battery in older adults specifically, and it will assess changes in metabolic and biochemical parameters during follow-up, including HbA1c, fasting glucose, lipid profile, and C-reactive protein. Other secondary aims are to develop a predictive model for appendicular lean mass loss and fat regain based on clinical and body composition variables, and to explore the association between changes in appendicular muscle mass and glycemic control. At one of the two study sites only, the study will evaluate changes in resting energy expenditure measured by indirect calorimetry and their relationship with changes in body composition. The study will also evaluate sarcopenia risk using the SARC-F questionnaire, comparing scores of 0 to 10 and a threshold of 4 or higher, and how this evolves at 24 and 52 weeks, exploring its association with appendicular lean mass and the appendicular skeletal muscle index. Finally, as an exploratory analysis, and only among participants who choose to provide an optional blood sample described below, the study will look at whether a specific genetic variant, rs10305420 in the GLP1R gene, is associated with the size and pattern of longitudinal changes in body weight, body mass index, and appendicular lean mass.
This is a prospective, observational, multicenter cohort study conducted under routine clinical practice conditions, sometimes called a real world study. It is not a drug trial. The research team will not assign, adjust, or withhold any medication. Each participant's treating physician makes all treatment decisions, including which GLP-1 receptor agonist to prescribe, dosing, and any changes over time, based on clinical indication, current treatment guidelines, medication availability, coexisting conditions, and the patient's preferences. There is a single study group and no comparator or control group, and treatment assignment is not randomized.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Agrees to participate in the study by signing informed consent
- •Age 18 years or older
- •Diagnosis of obesity and/or type 2 diabetes mellitus, documented in the clinical record
- •Receiving, on indication of the treating physician and as part of routine clinical care, a therapy with activity on the GLP-1 receptor, including a) GLP-1 receptor monoagonists, b) dual GIP/GLP-1 coagonists, or c) other multiple coagonists with activity on the GLP-1 receptor holding current health authorization for clinical use in Mexico
- •Meeting one of the following conditions at the time of recruitment: a) starting an eligible therapy during the recruitment period, or b) being in an active dose titration phase, with an upward dose escalation documented by the treating physician, even if treatment started four or more weeks earlier, provided the participant has not yet reached a stable maintenance dose
- •Willingness and ability to attend follow up evaluations at 24 weeks (plus or minus 3 weeks) and 52 weeks (plus or minus 6 weeks)
排除标准
- •Diagnosis of type 1 diabetes or other specific forms of diabetes
- •Pregnancy or breastfeeding at the time of recruitment
- •Conditions that limit adequate measurement of body composition by DXA, including body weight above the equipment's technical limit of 159 kg, the presence of metallic devices or materials that interfere with the measurement, or having undergone a radiologic contrast study within the 7 days before the evaluation
- •Acute illness at the time of recruitment that could interfere with the study evaluations or with longitudinal follow up, including hospitalization within the 4 weeks before the baseline visit, active pneumonia, acute COVID-19 infection, diabetic ketoacidosis, or major surgery within the 6 weeks before recruitment
- •Chronic diseases or conditions associated with severe alterations in body composition, such as active cancer, active systemic inflammatory disease, advanced heart failure, or kidney disease on replacement therapy
- •Current or recent use, within 3 months, of systemic corticosteroids at chronic pharmacologic doses or medications with a direct modulating effect on muscle mass
- •Current or recent use, within 3 months before the index date, of weight loss medications other than GLP-1RA, such as phentermine, topiramate, or naltrexone/bupropion
- •Simultaneous participation in a double blind randomized clinical trial
研究组 & 干预措施
Adults Initiating GLP-1-Based Therapy
Adults with obesity and/or type 2 diabetes who are starting GLP-1 receptor agonist therapy, or who are in the early phase of dose titration at the time of enrollment, based on the eligibility criteria defined in the protocol. Participants are followed prospectively for 52 weeks. The choice of treatment, dose adjustments, and overall clinical management are made by the treating physician as part of routine clinical care, and are not assigned by the study.
结局指标
主要结局
Change in Appendicular Lean Mass
时间窗: Baseline, 24 weeks, and 52 weeks
Change in appendicular lean mass, measured in kilograms by dual energy X-ray absorptiometry (DXA).
Change in Appendicular Skeletal Muscle Index (ASMI)
时间窗: Baseline, 24 weeks, and 52 weeks
Change in the appendicular skeletal muscle index, calculated as appendicular lean mass divided by height squared (kg/m²), measured by DXA.
次要结局
- Change in Total Fat Mass(Baseline, 24 weeks, and 52 weeks)
- Change in Body Fat Percentage(Baseline, 24 weeks, and 52 weeks)
- Change in Visceral Adipose Tissue (VAT)(Baseline, 24 weeks, and 52 weeks)
- Change in Body Weight(Baseline, 24 weeks, and 52 weeks)
- Change in Body Mass Index (BMI)(Baseline, 24 weeks, and 52 weeks)
- Change in Muscle Strength(Baseline, 24 weeks, and 52 weeks)
- Change in Physical Performance and Functional Mobility(Baseline, 24 weeks, and 52 weeks)
- Change in Sarcopenia Risk(Baseline, 24 weeks, and 52 weeks)
- Change in Lumbar Spine Bone Mineral Density(Baseline, 24 weeks, and 52 weeks)
- Change in Hip Bone Mineral Density(Baseline, 24 weeks, and 52 weeks)
- Change in Metabolic and Biochemical Parameters(Baseline, 24 weeks, and 52 weeks)
- Change in Anthropometric Measurements(Baseline, 24 weeks, and 52 weeks)
- Change in Resting Energy Expenditure (REE)(Baseline, 24 weeks, and 52 weeks)
- Association Between Treatment Adherence and Body Composition Changes(Up to 52 weeks)
- Association Between Appendicular Muscle Mass and Glycemic Control(Baseline, 24 weeks, and 52 weeks)
- Association of GLP1R Variant rs10305420 with Body Composition Trajectory(Baseline through 52 weeks)