Table of Contents

ABSTRACT

Background: Diabetes mellitus is associated with hyper-glycemia, oxidative stress and an increased risk of cardio-vascular disease (CVDs). Administration of empagliflozin (EMPA) reduces blood glucose and blood pressure. Evidence is scarce regarding its role in chronotherapy. This observational study examines the effect of EMPA as chronotherapy in patients with type 2 diabetes mellitus (T2DM).

Subjects and Methods: This study included 63 subjects with T2DM, scheduled to receive EMPA. Of these, 57 received EMPA (25mg/day) for 24 weeks, of which 25 received the dose in the evening and 23 in the morning. Clinical data, dietary intake and physical activity were assessed using validated questionnaires. Blood pressures were measured by sphygmomanometer.

Results: Single blind therapy with EMPA was associated with a significant reduction in fasting and 2-hour post-prandial blood glucose levels and HbA1c. These changes were greater when EMPA was administered in the evening compared to morning. The reductions in pro-inflammatory cytokines, C-reactive proteins, TNF-alpha and interleukin-6, also showed greater and reductions when EMPA was administered in the evening, compared to morning and baseline levels. Chronotherapy with EMPA also caused a non-significant reduction in serum uric acid, systolic and diastolic blood pressures and angiotensin converting enzyme (ACE) levels when given in the evening compared to those patients who received EMPA in the morning.

Conclusion: Chronotherapy with EMPA causes a greater reduction in blood glucose, blood pressures, serum uric acid, HbA1c, cytokines and ACE when administered in the evening compared to values obtained when the same dose was administered in the morning. Randomized, controlled intervention trials should be carried out to confirm these observations.

Keywords: Hyperglycemia, cytokines, nutrition, inflammation, time adjusted therapy, circadian