Pharmacogenetics of SGLT2 Inhibitors

• Status: Active, not recruiting
• Trial end date: 2021-12-31
• Target enrollment: 0
• Participant gender: All

Summary

Sodium-dependent glucose transporter-2 (SGLT2) inhibitors are a new class of anti-diabetic drugs, which increase urinary glucose excretion thereby promoting weight loss and decreasing plasma glucose levels. We hypothesize that the pharmacodynamic response to SGLT2 inhibitors (specifically canagliflozin) varies among individuals, and that a proportion of this inter-individual variation can be explained by genetic variation. This is a pilot study in healthy, non-diabetic subjects in whom glucose and other related metabolites in the urine and plasma will be measured before and after administration of a single dose of canagliflozin. This will allow us to characterize the inter-individual variation in the pharmacodynamic response to canagliflozin as well as determine if changes in glucose and other related metabolite levels are associated with variants in various candidate genes.

• Phase: Phase 4
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: University of Maryland; University of Maryland, Baltimore
• Collaborator: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Treatments: Canagliflozin

Criteria

Inclusion Criteria:

• Of Amish descent

• Age 21 or older

• BMI 18-40 kg/m2

Exclusion Criteria:

• Known allergy to canagliflozin

• History of diabetes, random glucose greater than 200 mg/dL, or HbA1c greater than or equal to 6.5%

• Currently taking diuretics, antihypertensive medication, uric acid lowering medications, or other medication that the investigator judges will make interpretation of the results difficult

• Significant debilitating chronic cardiac, hepatic, pulmonary, or renal disease or other diseases that the investigator judges will make interpretation of the results difficult or increase the risk of participation

• Seizure disorder

• Positive urine human chorionic gonadotropin (hCG) test or known pregnancy within 3 months of the start of the study

• Estimated glomerular filtration rate less than 60 mL/min

• Currently breast feeding or breast feeding within 3 month of the start of the study

• Liver function tests greater than 2 times the upper limit of normal

• Hematocrit less than 35%

• Currently symptomatic for urinary tract or yeast infection or history of two or more urinary tract or yeast infections in the past 12 months.

• Abnormal thyroid stimulating hormone (TSH)