Effect of Metformin in Individuals With Type 2 Diabetes According to SLC16A11 Risk Variant Carrier Status
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 154
- 试验地点
- 1
- 主要终点
- Change in Glycated Hemoglobin (HbA1c)
研究概览
简要总结
This prospective observational study will evaluate whether the SLC16A11 risk variant influences the response to metformin in adults with type 2 diabetes. Participants will be classified as carriers or noncarriers and followed for 6 months while receiving extended-release metformin titrated to the maximum tolerated dose, between 1,500 and 2,250 mg/day. The primary outcome is the change in glycated hemoglobin, with additional assessment of seven-point capillary glucose profiles, liver enzymes, visceral fat, lipid profile, and lactate concentrations. The study plans to include 154 participants to compare treatment response between both genetic groups and explore the potential value of a more personalized therapeutic approach.
详细描述
Type 2 diabetes (T2D) is a major global health problem and is closely associated with obesity and an increased risk of microvascular and macrovascular complications. A risk haplotype located in the SLC16A11 gene has been associated with a higher susceptibility to T2D and may contribute substantially to the increased prevalence of the disease in the Mexican population. The SLC16A11 gene encodes a bidirectional solute transporter involved in the transport of monocarboxylates such as pyruvate and lactate. However, it is not yet clear whether this genetic variation influences the metabolic response to metformin.
This prospective, analytical, observational study aims to compare the effect of metformin treatment between adults with T2D who are carriers and noncarriers of the SLC16A11 risk variant. A total of 154 participants are planned to be included. Eligible participants will be men and women aged 18 to 65 years with T2D, glycated hemoglobin of 8% or lower, and an estimated glomerular filtration rate greater than 60 mL/min. Participants may be untreated or receiving metformin alone or as part of dual pharmacological therapy.
All participants will receive extended-release metformin with gradual dose titration according to tolerance. Treatment will begin with 750 mg at night during the first week, increase to 750 mg in the morning and 750 mg at night during the second week, and may reach 750 mg three times daily from the third week onward. The target dose will be the maximum tolerated dose, ranging from 1,500 to 2,250 mg/day. Telephone follow-up will be conducted during titration to assess tolerance and guide dose adjustment.
Participants will be followed for 6 months. The primary objective is to compare the change in glycated hemoglobin between carriers and noncarriers of the SLC16A11 risk variant. Additional outcomes will include the seven-point capillary glucose profile, liver enzymes, visceral fat, total cholesterol, triglycerides, HDL cholesterol, LDL cholesterol, and lactate concentrations.
The study is based on the hypothesis that carriers of the SLC16A11 risk variant will have a smaller reduction in glycated hemoglobin, estimated at 0.5 percentage points, after 6 months of metformin treatment compared with noncarriers. Understanding whether this genetic variant modifies the response to metformin may contribute to a more personalized therapeutic approach and improve knowledge of the mechanisms involved in metformin-mediated glucose regulation.
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 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male and female participants
- •Aged 18 to 65 years
- •Diagnosis of type 2 diabetes
- •Estimated glomerular filtration rate (eGFR) >60 mL/min
- •Glycated hemoglobin (HbA1c) ≤8%
- •Participants who are treatment-naïve, receiving metformin monotherapy, or receiving dual glucose-lowering therapy
- •Participants who agree to take part in the study
排除标准
- •Participants receiving treatment with three glucose-lowering medications
- •Participants receiving insulin therapy
- •Pregnancy
- •Breastfeeding
- •Chronic conditions such as HIV infection, cancer, or rheumatologic diseases, including systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA)
- •Body mass index (BMI) ≥45 kg/m²
- •Concurrent participation in another research study
研究组 & 干预措施
SLC16A11 Risk Variant Carriers
Individuals with type 2 diabetes who carry the SLC16A11 risk variant and receive metformin treatment as part of their clinical management.
SLC16A11 Risk Variant Noncarriers
Individuals with type 2 diabetes who do not carry the SLC16A11 risk variant and receive metformin treatment as part of their clinical management.
结局指标
主要结局
Change in Glycated Hemoglobin (HbA1c)
时间窗: Baseline, Week 12, and Week 24
Change in glycated hemoglobin (HbA1c), expressed as percentage points, from baseline to Week 12 and Week 24. Changes will be compared between participants with type 2 diabetes who are carriers and non-carriers of the SLC16A11 risk variant.
次要结局
- Change in Fasting Plasma Glucose(Baseline, Week 12, and Week 24)
- Change in Seven-Point Capillary Glucose Profile(Baseline and Week 24)
- Change in Alanine Aminotransferase (ALT)(Baseline, Week 12, and Week 24)
- Change in Aspartate Aminotransferase (AST)(Baseline, Week 12, and Week 24)
- Change in Gamma-Glutamyl Transferase (GGT)(Baseline, Week 12, and Week 24)
- Change in Total Cholesterol(Baseline, Week 12, and Week 24)
- Change in High-Density Lipoprotein Cholesterol(Baseline, Week 12, and Week 24)
- Change in Triglycerides(Baseline, Week 12, and Week 24)
- Change in Low-Density Lipoprotein Cholesterol(Baseline, Week 12, and Week 24)
- Change in Apolipoprotein B(Baseline and Week 24)
- Change in Blood Lactate Concentration(Baseline, Week 12, and Week 24)
- Change in Visceral Fat Mass(Baseline and Week 24)
研究者
Paloma Almeda-Valdés
Staff Physician and Investigator at the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán
Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran