Objectives To assess and compare the effects of candesartan or lisinopril, or both, on blood pressure and urinary albumin excretion in patients with microalbuminuria, hypertension, and type 2 diabetes. Design Prospective, randomised, parallel group, double blind study with four week placebo run in period and 12 weeks' monotherapy with candesartan or lisinopril followed by 12 weeks' monotherapy or combination treatment. Setting Tertiary hospitals and primary care centres in four countries (37 centres). Participants 199 patients aged 30-75 years. Interventions Candesartan 16 mg once daily, lisinopril 20 mg once daily. Main outcome measures Blood pressure and urinary albumin:creatinine ratio. Results At 12 weeks mean (95% confidence interval) reductions in diastolic blood pressure were 9.5 mm Hg (7.7 mm Hg to 11.2 mm Hg, P < 0.001) and 9.7 mm Hg (7.9 mm Hg to 11.5 mm Hg, P < 0.001), respectively, and in urinary albumin:creatinine ratio were 30% (15% to 42%, P < 0.001) and 46% (35% to 56%, P < 0.001) for candesartan and lisinopril, respectively. At 24 weeks the mean reduction in diastolic blood pressure with combination treatment (16.3 mm Hg, 13.6 mm Hg to 18.9 mm Hg, P < 0.001) was significantly greater than that with candesartan (10.4 mm Hg, 7.7 mm Hg to 13.1 mm Hg, P < 0.001) or lisinopril (mean 10.7 mm Hg, 8.0 mm Hg to 13.5 mm Hg, P < 0.001). Furthermore, the reduction in urinary albumin:creatinine ratio with combination treatment (50%, 36% to 61%, P < 0.001) was greater than with candesartan (24%, 0% to 43%, P = 0.05) and lisinopril (39%, 20% to 54%, P < 0.001). All treatments were generally well tolerated. Conclusion Candesartan 16 mg once daily is as effective as lisinopril 20 mg once daily in reducing blood pressure and microalbuminuria in hypertensive patients with type 2 diabetes. Combination treatment is well tolerated and more effective in reducing blood pressure.

OBJECTIVETo investigate the efficacy, safety, and tolerability of empagliflozin in patients with type 2 diabetes and hypertension. RESEARCH DESIGN AND METHODSPatients (N = 825) with type 2 diabetes and hypertension (mean seated systolic blood pressure [SBP] 130-159 mmHg and diastolic blood pressure [DBP] 80-99 mmHg) were randomized (double blind) to 10 mg or 25 mg empagliflozin or placebo once daily for 12 weeks. RESULTSAt week 12, adjusted mean difference versus placebo in change from baseline in mean 24-h SBP (ambulatory blood pressure monitoring [ABPM]) was 23.44 mmHg (95% CI 24.78, 22.09) with 10 mg empagliflozin and 24.16 mmHg (25.50, 22.83) with 25 mg empagliflozin (both P < 0.001). At week 12, adjusted mean difference versus placebo in change from baseline in mean 24-h DBP (ABPM) was 21.36 mmHg (95% CI 22.15, 20.56) with 10 mg empagliflozin and 21.72 mmHg (95% CI 22.51, 20.93) with 25 mg empagliflozin (both P < 0.001). Changes in office BP were consistent with ABPM. Adjusted mean difference versus placebo in change from baseline in HbA 1c at week 12 was 20.62% (95% CI 20.72, 20.52) (26.8 mmol/mol [95% CI 27.9, 25.7]) with 10 mg empagliflozin and 20.65% (95% CI 20.75, 20.55) (27.1 mmol/mol [95% CI 28.2, 26.0]) with 25 mg empagliflozin (both P < 0.001). Empagliflozin was well tolerated. One patient on placebo and one patient on 10 mg empagliflozin reported events consistent with volume depletion. CONCLUSIONSEmpagliflozin was associated with significant and clinically meaningful reductions in BP and HbA 1c versus placebo and was well tolerated in patients with type 2 diabetes and hypertension.The lifetime risk of cardiovascular disease in patients with diabetes is 67-78% (1). Management of patients with type 2 diabetes should not only aim to control glycemia but also include the modification of cardiovascular risk factors (2,3). Hypertension affects approximately two-thirds of patients with diabetes (4,5) and is a significant contributing factor to cardiovascular complications (3,6). Lowering blood pressure (BP) has been shown to reduce cardiovascular events in patients with diabetes and to exert a renoprotective effect (3,7,8). The Joint National Committee (JNC) 2003 guidelines recommended targets of systolic BP (SBP) ,130 mmHg and diastolic BP (DBP) ,80 mmHg in patients with hypertension and diabetes (9). The guidelines

We investigated the role of cardiomyocyte apoptosis in the remodeling of the left ventricle from 24 h to 12 wk after myocardial infarction in the rat. Infarct size planimetry, quantification of cardiomyocyte apoptosis, terminal deoxynucleotide transferase-mediated dUTP nick-end labeling (TUNEL) methodology, and echocardiography (left ventricular diastolic diameter and ejection fraction) were performed. Sham-operated animals showed low rates of cardiomyocyte apoptosis (0.03%) and no change in diastolic diameter or ejection fraction during the study. Twenty-four hours after infarction, TUNEL positivity was high in the infarct areas (1.4%) and border zones (4.9%). It declined to 0.34% (P < 0.01 vs. sham) at 4 wk and 0.10% at 12 wk in the border zones. In the remote myocardium, cardiomyocyte apoptosis increased to 0.07% (P = 0.03 vs. sham) on day 1 and remained on the same level up to 4 wk. The increase in diastolic diameter 1-4 wk after infarction correlated (r = 0.60, P < 0.01) with cardiomyocyte apoptosis in the noninfarcted myocardium, which quantitatively contributed most (>50%) to the apoptotic cell loss by 4 wk.

Sodium glucose cotransporter 2 (SGLT2) inhibitors reduce HbA1c, blood pressure, and weight in patients with type 2 diabetes. To investigate the effect of renal function on reductions in these parameters with the SGLT2 inhibitor empagliflozin, we assessed subgroups by baseline estimated glomerular filtration rate (eGFR; Modification of Diet in Renal Disease) in pooled data from five 24-week trials of 2286 patients with type 2 diabetes randomized to empagliflozin or placebo. Reductions in HbA1c with empagliflozin versus placebo significantly diminished with decreasing baseline eGFR. Reductions in systolic blood pressure (SBP) with empagliflozin were maintained in patients with lower eGFR. The mean placebo-corrected changes from baseline in systolic blood pressure at week 24 with empagliflozin were -3.2 (95% confidence interval -4.9,-1.5) mmHg, -4.0 (-5.4, -2.6) mmHg, -5.5 (-7.6, -3.4) mmHg, and -6.6 (-11.4, -1.8) mmHg in patients with an eGFR of 90 or more, 60 to 89, 30 to 59, and under 30 ml/min/1.73m, respectively. Similar trends were observed for diastolic blood pressure. Weight loss with empagliflozin versus placebo tended to be attenuated in patients with a lower eGFR. Results were consistent in a 12-week ambulatory blood pressure monitoring trial in 823 patients with type 2 diabetes and hypertension. Thus, unlike HbA1c reductions, systolic blood pressure and weight reductions with empagliflozin are generally preserved in patients with chronic kidney disease.