Exercise is frequently prescribed as a favorable lifestyle intervention to prevent/reverse type 2 diabetes. It is also prescribed in addition to concurrent pharmacological treatment, such as metformin. Recent data (animal and human) suggest that metformin may attenuate the favorable benefits of exercise training. In light of the physiological mechanism of Dapagliflozin (sodium-glucose co-transporter 2 (SGLT2) inhibition), one might speculate that rather than inhibit, it will augment the favorable adaptations to exercise training.
This is a randomized, placebo-controlled, double blind, repeated measures study. 30 sedentary adults will be recruited for participation and randomly assigned to one of two 12-week treatments: 1) supervised endurance exercise training 4 days per week plus daily oral administration of Dapagliflozin; 2) supervised endurance exercise training 4 days per week plus daily oral administration of placebo. Prior to and following completion of the treatment the following dependent variables will be quantified: a) maximal aerobic capacity; b) substrate utilization during standardized low-moderate intensity exercise; c) skeletal muscle aerobic enzyme activity; d) body composition; and, e) oral glucose tolerance, fasting glucose and insulin resistance. The dose of Dapagliflozin will begin as 5 mg/day for the first 14-days. In the absence of complications, side effects, or unfavorable reactions, the dose will then increase to 10 mg/day for the remainder of the study.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
TRIPLE
Enrollment
37
Dapagliflozin tablets, 5 mg, one per day for the first 14 days, increase to two per day for 70 days.
Matching placebo for Dapagliflozin 5 mg, one per day for the first 14 days, increase to two per day for 70 days.
Colorado State University, Dept. of Health and Exercise Science
Fort Collins, Colorado, United States
Change From Baseline of Maximal Oxygen Uptake at Week 12
Indirect calorimetry
Time frame: Baseline,12 weeks
Change From Baseline of Respiratory Exchange Ratio at Week 12
The respiratory exchange ratio (RER) is the ratio between the amount of carbon dioxide (CO2) produced in metabolism and oxygen (O2) used during standardized exercise.
Time frame: Baseline, 12 weeks
Change From Baseline of Maximal Aerobic Enzyme Activities in Skeletal Muscle at Week 12
Maximal citrate synthase activity in skeletal muscle sample
Time frame: Baseline, 12 weeks
Change From Baseline of Insulin Sensitivity at Week 12
Insulin Sensitivity was estimated by measuring circulating glucose and insulin concentrations after a 12-hour fast and after ingestion of 75 g of glucose. Glucose was measured 5, 10, 15, 20, 30, 45, 60, 75, 90, 105 and 120 minutes after glucose ingestion. Insulin was measured 15, 30, 45, 60, 90 and 120 minutes after glucose ingestion. Insulin sensitivity was estimated using the Matsuda Index, represented by the formula: Matsuda index = 10,000/SQRT \[fasting glucose\*fasting insulin\* (mean glucose from time 5, 10, 15, 20, 30, 45, 60, 75, 90, 105 and 120 minutes) \* (mean insulin from time 15, 30, 45, 60, 90 and 120 minutes)\], with higher numbers indicating better insulin sensitivity.
Time frame: Baseline, 12 weeks
Change From Baseline of Fat Free Mass at Week 12
Via dual energy X-ray absorptiometry
Time frame: Baseline, 12 weeks
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