Influence of Sodium Glucose Cotransporter 2 Inhibition on Physiological Adaptation to Endurance Exercise Training
Open accessAbstract
CONTEXT: The combination of two beneficial antidiabetes interventions, regular exercise and pharmaceuticals, is intuitively appealing. However, metformin, the most commonly prescribed diabetes medication, attenuates the favorable physiological adaptations to exercise; in turn, exercise may impede the action of metformin. OBJECTIVE: We sought to determine the influence of an alternative diabetes treatment, sodium glucose cotransporter 2 (SGLT2) inhibition, on the response to endurance exercise training. DESIGN, PARTICIPANTS, AND INTERVENTION: In a randomized, double-blind, repeated measures parallel design, 30 sedentary overweight and obese men and women were assigned to 12 weeks of supervised endurance exercise training, with daily ingestion of either a placebo or SGLT2 inhibitor (dapagliflozin: ≤10 mg/day). OUTCOME MEASUREMENTS AND RESULTS: Endurance exercise training favorably modified body mass, body composition (dual-energy x-ray absorptiometry), peak oxygen uptake (graded exercise with indirect calorimetry), responses to standardized submaximal exercise (indirect calorimetry, heart rate, and blood lactate), and skeletal muscle (vastus lateralis) citrate synthase activity (main effects of exercise training, all P < 0.05); SGLT2 inhibition did not influence any of these physiological adaptations (exercise training × treatment interaction, all P > 0.05). However, after endurance exercise training, fasting blood glucose was greater with SGLT2 inhibition, and increased insulin sensitivity (oral glucose tolerance test/Matsuda index) was abrogated with SGLT2 inhibition (exercise training × treatment interaction, P < 0.01). CONCLUSION: The efficacy of combining two beneficial antidiabetes interventions, regular endurance exercise and SGLT2 inhibition, was not supported. SGLT2 inhibition blunted endurance exercise training-induced improvements in insulin sensitivity, independent of effects on aerobic fitness or body composition.
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Metformin can diminish the improvement in aerobic capacity.
“Other common examples are: metformin can diminish the improvement in aerobic capacity, corticosteroids may lead to osteoporosis and muscle wasting, and chemotherapy agents can affect gait and balance through peripheral neuropathy [[553], [554], [555], [556], [557], [558]].”
From Global consensus on optimal exercise recommendations for enhancing healthy longevity in older adults (ICFSR) (2025) · cites this paper as [555]
Chemotherapy agents can affect gait and balance through peripheral neuropathy.
“Other common examples are: metformin can diminish the improvement in aerobic capacity, corticosteroids may lead to osteoporosis and muscle wasting, and chemotherapy agents can affect gait and balance through peripheral neuropathy [[553], [554], [555], [556], [557], [558]].”
From Global consensus on optimal exercise recommendations for enhancing healthy longevity in older adults (ICFSR) (2025) · cites this paper as [555]
Corticosteroids may lead to osteoporosis and muscle wasting.
“Other common examples are: metformin can diminish the improvement in aerobic capacity, corticosteroids may lead to osteoporosis and muscle wasting, and chemotherapy agents can affect gait and balance through peripheral neuropathy [[553], [554], [555], [556], [557], [558]].”
From Global consensus on optimal exercise recommendations for enhancing healthy longevity in older adults (ICFSR) (2025) · cites this paper as [555]
Metformin can diminish improvement in aerobic capacity; corticosteroids may lead to osteoporosis and muscle wasting; chemotherapy agents can affect gait and balance through peripheral neuropathy.
“Other common examples are: metformin can diminish the improvement in aerobic capacity, corticosteroids may lead to osteoporosis and muscle wasting, and chemotherapy agents can affect gait and balance through peripheral neuropathy [[553], [554], [555], [556], [557], [558]].”
From Global consensus on optimal exercise recommendations for enhancing healthy longevity in older adults (ICFSR) (2025) · cites this paper as [555]
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References 71 · Cited by 50
Research works printed but not linked: 1
- Bekki M, Tahara N, Tahara A, Igata S, Honda A, Sugiyama Y, Nakamura T, Sun J, Kumashiro Y, Matsui T, Fukumoto Y, Yamagishi S-I. Switching dipeptidyl peptidase-4 inhibitors to tofogliflozin, a selective inhibitor of sodium-glucose cotransporter 2 improves arterial stiffness evaluated by cardio-ankle vascular index in patients with type 2 diabetes: a pilot study [published online ahead of print 15 May 2018]. Curr Vasc Pharmacol. doi: 10.2174/1570161116666180515154555. · DOI
- Authors
- Newman, A. A., Grimm, N. C., Wilburn, J. R., Schoenberg, H. M., Trikha, S. R. J., Luckasen, G. J., Biela, L. M., Melby, C. L., & Bell, C.
- Affiliations
- Colorado State University (US)
- University of Colorado Health (US)
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2018-12-28
- Volume
- 104
- Issue
- 6
- Pages
- 1953-1966
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W2908170356
- Cited by
- 50
- References
- 71
- Citations by year
- 2026: 5 · 2025: 8 · 2024: 7 · 2023: 7 · 2022: 8 · 2021: 5 · 2020: 5 · 2019: 4
- FWCI
- 4.81
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Funders
- AstraZeneca Pharmaceuticals LP
- Topics
- Health Sciences › Medicine › Complementary and alternative medicine › Cardiovascular and exercise physiology
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- SGLT2 inhibition, dapagliflozin, endurance training, insulin sensitivity, type 2 diabetes, obesity, peak oxygen uptake, body composition, fasting blood glucose, citrate synthase, skeletal muscle
- MeSH terms
- Endurance Training, Sodium-Glucose Transporter 2 Inhibitors, Adaptation, Physiological, Adolescent, Adult, Benzhydryl Compounds, Blood Glucose, Combined Modality Therapy, Diabetes Mellitus, Type 2, Double-Blind Method, Exercise Therapy, Female, Glucosides, Humans, Insulin, Insulin Resistance, Male, Middle Aged, Physical Endurance, Treatment Outcome, Sodium-Glucose Transporter 2, Young Adult, Sedentary Behavior
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