Study to Understand the Genetics of the Acute Response to Metformin and Glipizide in Humans

• Status: Unknown status
• Trial end date: 2017-10-01
• Target enrollment: 0
• Participant gender: All

Summary

The SUGAR-MGH investigators are studying the influence of inherited gene variants on the response to two commonly prescribed type 2 diabetes medications, metformin and glipizide. They hypothesize that variants in genes that are associated with type 2 diabetes or related traits may impact the effect of anti-diabetic medications. In addition, physiological responses to an insulin secretagogue or an insulin sensitizer may shed light on the mechanism of action of reported genetic associations.

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Massachusetts General Hospital
• Collaborators: Brigham and Women's Hospital; Broad Institute; Joslin Diabetes Center
• Treatments: Glipizide; Metformin

Criteria

Inclusion Criteria:

• Male or non-pregnant female > 18 years of age

• Investigators will target preferentially people at risk of diabetes or requiring diabetes meds

• The first tier of risk will be illustrated by one of the following variables (e.g. established type 2 diabetes on diet therapy alone, elevated random glucose in electronic medical record, PCOS, metabolic syndrome, obesity, history of gestational diabetes, etc.)

• The second tier of risk will be illustrated by other features that correlate with diabetes risk, such as a history of hypertension or dyslipidemia

• Otherwise healthy subjects may also be candidates for the study.

• Able and willing to give consent relevant to genetic investigation

Exclusion Criteria:

• Pregnant, nursing or at risk of becoming pregnant

• Currently taking any medications for the treatment of diabetes

• Currently on metformin for any other indication (e.g. PCOS)

• Onset of diabetes in a family member before age 25, with autosomal transmission of diabetes across three generations

• History of liver or kidney disease

• Known severe allergic reactions to sulfonamides

• History of porphyria

• Documented estimated glomerular filtration rate (GFR) < 60 ml/min/1.73 m2, based on the most recent serum creatinine measurement available in the electronic medical record, and calculated by the Modification of Diet in Renal Disease equation (49) available at http://www.nephron.com/cgi-bin/MDRD_GFR.cgi

• Currently taking medications known to affect glycemic parameters, such as glucocorticoids, growth hormone or fluoroquinolones

• Planned radiologic or angiographic study requiring contrast within one week of completion of this study

• Established coronary artery disease (CAD), defined as:

• History of myocardial infarction.

• History of revascularization (coronary artery bypass grafting, percutaneous coronary intervention (e.g. stenting or balloon angioplasty).

• Evidence of ischemia on cardiac stress test.

• Enrolled in any other interventional study at time of screening through completion of study protocol

• History of bariatric surgery

• History of seizures

• History of stroke/CVA