Metformin Effects According to SLC16A11 Carrier Status

NCT07760883 | Recruiting

• 1 other identifier: 3486
• Study Type: observational
• Target: 154
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Diabetes Type 2

Keywords

diabetes type 2; metformin; SLC16A11; glycated hemoglobin

Outcome Measures

Primary Outcomes (1)

• Change in Glycated Hemoglobin (HbA1c)

  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.

  Baseline, Week 12, and Week 24

Secondary Outcomes (12)

• 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

Study Arms (2)

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.

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Adults aged 18 to 65 years with type 2 diabetes and glycated hemoglobin (HbA1c) ≤8%. Participants may be treatment-naïve, receiving metformin monotherapy, or receiving dual glucose-lowering therapy, and must have an estimated glomerular filtration rate (eGFR) \>60 mL/min.

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran: lead

Study Sites (1)

Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán

Mexico City, Mexico City, 14080, Mexico

RECRUITING

Related Publications (19)

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  PMID: 37130947 BACKGROUND

• Kim H, Bae S, Yoon HY, Yee J, Gwak HS. Association of the SLC47A1 Gene Variant With Responses to Metformin Monotherapy in Drug-naive Patients With Type 2 Diabetes. J Clin Endocrinol Metab. 2022 Aug 18;107(9):2684-2690. doi: 10.1210/clinem/dgac333.

  PMID: 35639991 BACKGROUND

• Rusu V, Hoch E, Mercader JM, Tenen DE, Gymrek M, Hartigan CR, DeRan M, von Grotthuss M, Fontanillas P, Spooner A, Guzman G, Deik AA, Pierce KA, Dennis C, Clish CB, Carr SA, Wagner BK, Schenone M, Ng MCY, Chen BH; MEDIA Consortium; SIGMA T2D Consortium; Centeno-Cruz F, Zerrweck C, Orozco L, Altshuler DM, Schreiber SL, Florez JC, Jacobs SBR, Lander ES. Type 2 Diabetes Variants Disrupt Function of SLC16A11 through Two Distinct Mechanisms. Cell. 2017 Jun 29;170(1):199-212.e20. doi: 10.1016/j.cell.2017.06.011.

  PMID: 28666119 BACKGROUND

• Fontaine E. Metformin-Induced Mitochondrial Complex I Inhibition: Facts, Uncertainties, and Consequences. Front Endocrinol (Lausanne). 2018 Dec 17;9:753. doi: 10.3389/fendo.2018.00753. eCollection 2018.

  PMID: 30619086 BACKGROUND

• SIGMA Type 2 Diabetes Consortium; Williams AL, Jacobs SB, Moreno-Macias H, Huerta-Chagoya A, Churchhouse C, Marquez-Luna C, Garcia-Ortiz H, Gomez-Vazquez MJ, Burtt NP, Aguilar-Salinas CA, Gonzalez-Villalpando C, Florez JC, Orozco L, Haiman CA, Tusie-Luna T, Altshuler D. Sequence variants in SLC16A11 are a common risk factor for type 2 diabetes in Mexico. Nature. 2014 Feb 6;506(7486):97-101. doi: 10.1038/nature12828. Epub 2013 Dec 25.

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• Pearson ER. Diabetes: Is There a Future for Pharmacogenomics Guided Treatment? Clin Pharmacol Ther. 2019 Aug;106(2):329-337. doi: 10.1002/cpt.1484.

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• Mofo Mato EP, Guewo-Fokeng M, Essop MF, Owira PMO. Genetic polymorphisms of organic cation transporter 1 (OCT1) and responses to metformin therapy in individuals with type 2 diabetes: A systematic review. Medicine (Baltimore). 2018 Jul;97(27):e11349. doi: 10.1097/MD.0000000000011349.

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  PMID: 28321905 BACKGROUND

• Taheri R, Kazerouni F, Mirfakhraei R, Kalbasi S, Shahrokhi SZ, Rahimipour A. The influence of SLC22A3 rs543159 and rs1317652 genetic variants on metformin therapeutic efficacy in newly diagnosed patients with type 2 diabetes mellitus: 25 weeks follow-up study. Gene. 2022 May 20;823:146382. doi: 10.1016/j.gene.2022.146382. Epub 2022 Feb 28.

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• Li X, Yang Y, Zhang B, Lin X, Fu X, An Y, Zou Y, Wang JX, Wang Z, Yu T. Lactate metabolism in human health and disease. Signal Transduct Target Ther. 2022 Sep 1;7(1):305. doi: 10.1038/s41392-022-01151-3.

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• Abrahams-October Z, Johnson R, Benjeddou M, Cloete R. The determination of the effect(s) of solute carrier family 22-member 2 (SLC22A2) haplotype variants on drug binding via molecular dynamic simulation systems. Sci Rep. 2022 Oct 8;12(1):16936. doi: 10.1038/s41598-022-21291-4.

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• He L, Wondisford FE. Metformin action: concentrations matter. Cell Metab. 2015 Feb 3;21(2):159-162. doi: 10.1016/j.cmet.2015.01.003.

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• LaMoia TE, Shulman GI. Cellular and Molecular Mechanisms of Metformin Action. Endocr Rev. 2021 Jan 28;42(1):77-96. doi: 10.1210/endrev/bnaa023.

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• Resendiz-Abarca CA, Flores-Alfaro E, Suarez-Sanchez F, Cruz M, Valladares-Salgado A, Del Carmen Alarcon-Romero L, Vazquez-Moreno MA, Wacher-Rodarte NA, Gomez-Zamudio JH. Altered Glycemic Control Associated With Polymorphisms in the SLC22A1 (OCT1) Gene in a Mexican Population With Type 2 Diabetes Mellitus Treated With Metformin: A Cohort Study. J Clin Pharmacol. 2019 Oct;59(10):1384-1390. doi: 10.1002/jcph.1425. Epub 2019 Apr 23.

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• Foretz M, Guigas B, Viollet B. Understanding the glucoregulatory mechanisms of metformin in type 2 diabetes mellitus. Nat Rev Endocrinol. 2019 Oct;15(10):569-589. doi: 10.1038/s41574-019-0242-2. Epub 2019 Aug 22.

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  PMID: 22722338 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Whole blood, serum, plasma, and extracted genomic DNA will be retained. Genomic DNA will be used for SLC16A11 risk variant genotyping.

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Central Study Contacts

Paloma Almeda Valdés, MD, PhD

CONTACT

525554870900; paloma.almedav@incmnsz.mx

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Staff Physician and Investigator at the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán

Study Record Dates

• First Submitted: August 5, 2026
• First Posted: August 12, 2026
• Study Start: September 23, 2020
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: August 12, 2026

Record last verified: 2026-08

Locations

ME (1)