Genetic Variation in OCT1 and Response to Metformin
- Full Text View
- Tabular View
- No Study Results Posted
- Disclaimer
- How to Read a Study Record
Type 2 diabetes its microvascular and macrovascular complications have become a major global health problem. Metformin is often used as first-line therapy for this disorder given that it is cheap, may cause weight loss and does not have significant side-effects in healthy patients. On the other hand, as many as one third of all patients with type 2 diabetes initially treated with metformin never achieve a meaningful response to this intervention. Recently, genetic variation in the organic cation transporter 1 (Oct1) gene which encodes a protein, OCT1, mediating metformin uptake by the liver, its primary site of action, has been shown alter metformin action. In Oct1-deficient mice the glucose-lowering effects of metformin are completely abolished. Moreover a polymorphism with a 20% minor allele frequency in Caucasians also alters the effect of metformin on glucose tolerance (the net result of glucose uptake and glucose release) after ingestion of 75g of glucose. However, it is unknown if this polymorphism affects suppression of endogenous glucose production or stimulation of peripheral glucose uptake by metformin, or both, and to what degree. We propose to utilize established methodology to measure glucose turnover in response to a mixed meal to determine how common genetic variation in OCT1 alters response to metformin in healthy volunteers. This will clarify the effect of these variants on response to metformin in humans. The knowledge gained from this study will help to design future studies examining the role of OCT1 genotype in determining initial therapy for type 2 diabetes.
Condition | Intervention | Phase |
---|---|---|
Type 2 Diabetes |
Drug: Metformin |
Phase 4 |
Study Type: | Interventional |
Study Design: | Allocation: Non-Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Basic Science |
Official Title: | Genetic Variation in OCT1 and Response to Metformin |
- Change in glucose area under the curve after a mixed meal in response to metformin [ Time Frame: before and after 1 week of metformin ] [ Designated as safety issue: No ]
- Change in glucose disappearance and suppression of endogenous glucose production in response to metformin [ Time Frame: before and after 1 week of metformin therapy ] [ Designated as safety issue: No ]
Enrollment: | 0 |
Study Start Date: | June 2010 |
Estimated Study Completion Date: | June 2011 |
Primary Completion Date: | June 2010 (Final data collection date for primary outcome measure) |
Arms | Assigned Interventions |
---|---|
Sham Comparator: 1
Individuals with no nsSNPs or mutations known to alter oct1 function
|
Drug: Metformin
1000mg bid for 1 week
|
Active Comparator: 2
Individuals with nsSNPs or mutations known to alter oct1 function
|
Drug: Metformin
1000mg bid for 1 week
|
Ages Eligible for Study: | 18 Years to 70 Years |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | Yes |
Inclusion criteria: -
- Heterozygous or homozygous for the nsSNPs R61C, G401S, 420Del, G465R, G174S (see supplementary info (3)) or without any nsSNPs that could potentially alter gene function.
- Age 18 - 40.
- Willingness to participate in this study.
Exclusion criteria: -
- Fasting glucose > 100mg/dL on one occasion.
- Use of medication other than stable thyroid hormone replacement or oral contraception.
- Subjects must not be pregnant or < 6 months postpartum at the time of study.
- Prior abdominal surgery other than hysterectomy, appendectomy or tubal ligation.
Additional Information:
No publications provided
Responsible Party: | Adrian Vella MD, Mayo Clinic |
ClinicalTrials.gov Identifier: | NCT00588172 History of Changes |
Other Study ID Numbers: | 07-004310, OCT1 and metformin |
Study First Received: | December 22, 2007 |
Last Updated: | August 16, 2010 |
Health Authority: | United States: Food and Drug Administration |
Keywords provided by Mayo Clinic:
Metformin Type 2 diabetes Oct1 |
Additional relevant MeSH terms:
Diabetes Mellitus Diabetes Mellitus, Type 2 Glucose Metabolism Disorders Metabolic Diseases Endocrine System Diseases |
Metformin Hypoglycemic Agents Physiological Effects of Drugs Pharmacologic Actions |
ClinicalTrials.gov processed this record on October 17, 2012