How Does SGLT2 Inhibition Affect Exercise Training Outcomes?

Use of SGLT2 inhibitor dapagliflozin did not attenuate or augment any beneficial physiologic adaptations from endurance exercise training in overweight or obese adults.

Sodium glucose cotransporter-2 (SGLT2) inhibition is not an effective supplement to endurance exercise, according to study results published in The Journal of Clinical Endocrinology & Metabolism.

To determine the effects of an alternative diabetes treatment, such as SGLT2 inhibition, on physiologic adaptations to exercise, researchers randomly assigned 30 sedentary adults age 18 to 50 years who were overweight or obese but otherwise healthy to receive 12 weeks of endurance exercise training and a daily dose of placebo or dapagliflozin (≤10 mg).

There were no significant baseline differences between groups. The groups demonstrated similar exercise training compliance (P >.10) and exercising heart rate data across the 12 weeks, and medication compliance was 100% for both groups. Exercise training in both groups yielded overall reductions in mass, body mass index, fat mass, body fat percentage, and waist circumference (P ≤.01). There were also significant improvements in peak oxygen uptake, responses to standardized submaximal exercise, and skeletal muscle citrate synthase activity (all P <.05).

SGLT2 inhibition was deemed not to have significantly influenced any of the above changes (all P >.05). Compared with placebo, however, the treatment group did experience elevated fasting blood glucose after exercise, and dapagliflozin negated improvements in insulin sensitivity related to exercise (P <.006).

Limitations to this study included the potential for insulin resistance in an overweight/obese but diabetes-free population.

Summarizing their findings, the researchers said, “SGLT2 inhibition did not attenuate nor augment any of these beneficial physiological adaptations, with the notable exceptions of increasing fasting glucose relative to placebo, and abrogating the desirable change in insulin sensitivity [post-exercise]… baseline health status and final goals for concomitant prescription of exercise and SGLT2 inhibition may need to be considered carefully prior to initiation.”

AstraZeneca Pharmaceuticals LP provided financial support for this investigator-initiated study.

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Newman AA, Grimm NC, Wilburn JR, et al. Influence of sodium glucose co-transporter 2 inhibition on the physiological adaptation to endurance exercise training [published online December 28, 2018]. J Clin Endocrinol Metab. doi:10.1210/jc.2018-01741