In a Phase III randomized trial (EMPA-REG BP™), patients with type 2 diabetes (T2DM) and hypertension (defined as mean seated office systolic blood pressure [SBP] 130-159 mmHg and diastolic BP [DBP] 80-99 mmHg at screening) received empagliflozin (EMPA) 10 mg (n=276), EMPA 25 mg (n=276) or placebo (PBO; n=271) once daily in the morning for 12 weeks (mean [SD] age 60.2 [9.0] yrs, HbA1c 7.90 [0.74] %, 24-h SBP 131.4 [12.3] mmHg, 24-h DBP 75.0 [7.8] mmHg). We assessed changes from baseline in SBP (mean 24-h, awake-time, sleep-time) via ambulatory BP monitoring at week 12 in patients categorized as dippers (sleep-time mean SBP ≤90% of awake-time mean; n=417) or non-dippers (sleep-time mean SBP >90% of awake-time mean; n=350).
Baseline mean (SD) 24-h SBP (mmHg) was 129.9 (11.6) in dippers and 133.1 (12.4) in non-dippers. Adjusted mean (SE) changes from baseline in mean 24-h SBP (mmHg) in dippers were -0.2 (0.7) with PBO vs -3.8 (0.6) and -3.9 (0.7) with EMPA 10 and 25 mg, respectively (both p<0.001), and in non dippers were 1.0 (0.7) with PBO vs -1.6 (0.7) with EMPA 10 mg (p=0.013) and -3.8 (0.7) with EMPA 25 mg (p<0.001). Hourly mean SBP patterns over 24 h for dippers and non-dippers were maintained with EMPA 25 mg (Figure) and 10 mg. Adjusted mean (SE) changes from baseline in awake-time SBP (mmHg) in dippers were -0.5 (0.7) with PBO vs -4.6 (0.7) with EMPA 10 and 25 mg (both p<0.001), and in non dippers were 1.3 (0.8) with PBO vs -2.2 (0.8) with EMPA 10 mg (p=0.002) and -4.2 (0.7) with EMPA 25 mg (p<0.001). Adjusted mean (SE) changes from baseline in sleep-time SBP (mmHg) in dippers were 0.4 (0.8) with PBO vs -2.6 (0.8) with EMPA 10 mg (p=0.007) and -2.2 (0.8) with EMPA 25 mg (p=0.022), and in non-dippers were 0.1 (0.9) with PBO vs -0.5 (0.9) with EMPA 10 mg (p=0.603) and -3.2 (0.8) with EMPA 25 mg (p=0.006). There were no apparent differences in heart rate with EMPA vs PBO in dippers or non-dippers.
In patients with T2DM and hypertension, EMPA 10 mg and 25 mg significantly reduced SBP vs PBO in dippers and non-dippers.
Effects of Morning versus Evening Administration of Perindopril on the Circadian Control of Blood Pressure in Cameroonian Type 2 Diabetes Individuals: A Crossover Randomized Trial
