***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
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    Input: Background Azilsartan medoxomil ( AZL-M ) , has been demonstrated to be more effective than the other sartans currently in use ; however , there is insufficient information available comparing it with ACE-inhibitors . Therefore , we aim ed to compare the efficacy , safety , and tolerability of AZL-M with that of ACE-inhibitors in a real life clinical setting . Methods The EARLY registry is a prospect i ve , observational , national , multicentre registry with a follow-up period of 12 months . There were two principal objectives : 1 ) documentation of the achievement of target BP values set according to recent national and international guidelines , and 2 ) description of the safety profile of AZL-M. Results A total of 3 849 patients with essential arterial hypertension were recruited from primary care offices in Germany . Patients who initiated monotherapy at baseline comprising either AZL-M or an ACE-inhibitor were included at a ratio of seven to three . Results demonstrated that a blood pressure target of < 140/90 mmHg was achieved by a significantly greater proportion of patients in the AZL-M group ( 61.1 % ) compared with the ACE-inhibitor group ( 56.4 % ; p < 0.05 ; OR , 1.21 ; 95 % CI , 1.03–1.42 ) , with this finding maintained after adjusting for differences in baseline characteristics . AZL-M appeared to have an equivalent safety profile to the ACE-inhibitors , with a similar incidence of adverse events in the two patient groups ( p = 0.73 ) . Conclusions These data add to the results of previous r and omized controlled clinical trials suggesting that , compared with other agents that target the renin – angiotensin system , AZL-M provides statistically significant albeit small improvements in blood pressure control We design ed this study to explore to what extent the excess risk of cardiovascular events in diabetic individuals is attributable to hypertension . We retrospectively analyzed prospect ively collected data from the Framingham original and offspring cohorts . Of the 1145 Framingham subjects newly diagnosed with diabetes mellitus who did not have a previous history of cardiovascular events , 663 ( 58 % ) had hypertension at the time that diabetes mellitus was diagnosed . During 4154 person-years of follow-up , 125 died , and 204 experienced a cardiovascular event .  Framingham participants with hypertension at the time of diabetes mellitus diagnosis exhibited higher rates of all-cause mortality ( 32 versus 20 per 1000 person-years ; P<0.001 ) and cardiovascular events ( 52 versus 31 per 1000 person-years ; P<0.001 ) compared with normotensive subjects with diabetes mellitus . After adjustment for demographic and clinical covariates , hypertension was associated with a 72 % increase in the risk of all-cause death and a 57 % increase in the risk of any cardiovascular event in individuals with diabetes mellitus . The population -attributable risk from hypertension in individuals with diabetes mellitus was 30 % for all-cause death and 25 % for any cardiovascular event ( increasing to 44 % and 41 % , respectively , if the 110 normotensive subjects who developed hypertension during follow-up were excluded from the analysis ) . In comparison , after adjustment for concurrent hypertension , the population -attributable risk from diabetes mellitus in Framingham subjects was 7 % for all-cause mortality and 9 % for any cardiovascular disease event . Although diabetes mellitus is associated with increased risks of death and cardiovascular events in Framingham subjects , much of this excess risk is attributable to coexistent hypertension A phase 3 , 26‐week , open‐label , titrate‐to‐target study ( n=418 ) assessed the safety of azilsartan medoxomil ( AZL‐M ) alone and with chlorthalidone ( CLD ) , followed by a 6‐week , double‐blind , placebo‐controlled reversal phase with change in clinic diastolic blood pressure ( DBP ) as the primary endpoint .  Target blood pressure ( BP ) was < 140/90 mm Hg ( < 130/80 mm Hg with diabetes/chronic kidney disease ) . AZL‐M was initiated at 40 mg once a day ( QD ) , force‐titrated to 80 mg at week 4 . CLD 25 mg QD could be added ( weeks 8–22 ) , if required , to reach target , followed by additional antihypertensives from week 12 . At the end of the open‐label phase , mean change in systolic BP (SBP)/DBP from baseline was −23/−16 mm Hg . The most common adverse events , irrespective of treatment , were dizziness ( 8.9 % ) and headache ( 7.2 % ) . Serious AEs were reported in eight patients ( 1.9 % ) . Consecutive creatinine elevations ≥50 % with values exceeding the upper limit of normal ( ULN ) were reported in nine ( 2.2 % ) patients . All returned to below the 50 % threshold ; most also returned to below the ULN after drug discontinuation . Mean DBP was maintained through the reversal phase in patients receiving AZL‐M , but increased with placebo ( difference : −7.8 mm Hg , 95 % confidence interval , −9.8 to −5.8 ; P<.001 ) . AZL‐M alone or with CLD  showed good long‐term safety and stable BP improvements in a titrate‐to‐target approach . BP improvements caused by AZL‐M therapy were safely reversible upon AZL‐M withdrawal Azilsartan medoxomil ( AZL-M ) is a unique angiotensin II receptor blocker ( ARB ) under development for the treatment of hypertension . To compare this ARB with another in the class , the authors studied the effects of AZL-M and valsartan ( VAL ) in 984 patients with primary hypertension in a r and omized , double-blind , multicenter study using ambulatory and clinic blood pressure ( BP ) measurements . The primary end point was change from baseline in 24-hour mean ambulatory systolic BP following 24 weeks of treatment . Hierarchical analysis testing for noninferiority was followed by superiority testing of AZL-M ( 80 mg then 40 mg ) vs VAL . The mean age of participants was 58 years , 52 % were men , and 15 % were black .  Baseline 24-hour mean systolic BP was similar ( approximately 145.6 mm Hg ) in each group . AZL-M 40 mg and 80 mg lowered 24-hour mean systolic BP ( -14.9 mm Hg and -15.3 mm Hg , respectively ) more than VAL 320 mg ( -11.3 mm Hg ; P<.001 for 40-mg and 80-mg comparisons vs VAL ) . Clinic systolic BP reductions were consistent with the ambulatory results ( -14.9 mm Hg for AZL-M 40 mg and -16.9 mm Hg for AZL-M 80 mg vs -11.6 mm Hg for VAL ; P=.015 and P<.001 , respectively ) . The reductions in 24-hour mean and clinic diastolic BPs were also greater with both doses of AZL-M than with VAL ( P≤.001 for all comparisons ) . Small , reversible changes in serum creatinine occurred more often with AZL-M than with VAL ; otherwise , safety and tolerability parameters were similar among the three groups . These data demonstrate that AZL-M across the effective dose range had superior efficacy to VAL at its maximal recommended dose without any meaningful increase in adverse events . These findings suggest that AZL-M could provide higher rates of hypertension control compared with other ARBs in the class Background : Angiotensin receptor blockers ( ARBs ) are preferred antihypertensive therapies in patients with type 2 diabetes mellitus ( T2DM ) .  Azilsartan medoxomil ( AZL-M ) is a potent ARB for the treatment of stages 1 - 2 hypertension . We compared the efficacy , safety , and metabolic effects of AZL-M to both valsartan ( VAL ) and olmesartan ( OLM ) , separately in patients with impaired fasting glucose ( prediabetes mellitus ) and T2DM . Methods : A pooled analysis of 3821 patients from three separate r and omized placebo-controlled trials comparing the effects of AZL-M ( 40 and 80 mg ) , OLM ( 40 mg ) , VAL ( 320 mg ) , and placebo on changes in ambulatory and clinic blood pressure ( BP ) among patients with hypertension and prediabetes mellitus or T2DM was performed . Two analysis pools were created to facilitate comparisons : Pool A included patients who received placebo , AZL-M or OLM and Pool B included those who received AZL-M or VAL . Within each pool , patients were stratified by glycemic subgroups ( normoglycemic , prediabetes mellitus , or T2DM ) based on hemoglobin A1c values . Changes from baseline in both 24-h and clinic SBP were the primary efficacy assessment s. Results : Baseline 24-h mean SBPs were approximately 145 and 146 mmHg in the prediabetes mellitus and T2DM subgroups , respectively ; corresponding clinic SBPs were approximately 158 and 159 mmHg . Baseline hemoglobin A1c values for each subgroup ( both pools ) were normoglycemic , 5.3 % ; prediabetes mellitus , 6.0 % ; and T2DM , 6.9 % . Changes from baseline in 24-h or clinic SBP were significantly greater with AZL-M , 80 mg compared with either OLM 40 mg or VAL 320 mg in all subgroups in each pool . Safety and tolerability were similar among the active treatment and placebo subgroups . Conclusion : These analyses indicate that AZL-M , 80 mg/day lowers SBP by a greater magnitude than OLM or VAL at maximally approved doses in patients with prediabetes mellitus and T2DM . These findings have important clinical implication s for this high-risk patient group Drug therapy often fails to control hypertension . Azilsartan medoxomil ( AZL-M ) is a newly developed angiotensin II receptor blocker with high efficacy and good tolerability . This double-blind , controlled , r and omised trial compared its antihypertensive efficacy and safety vs the angiotensin-converting enzyme inhibitor ramipril ( RAM ) in patients with clinic systolic blood pressure ( SBP ) 150–180 mm Hg . Patients were r and omised ( n=884 ) to 20 mg AZL-M or 2.5 mg RAM once daily for 2 weeks , then force-titrated to 40 or 80 mg AZL-M or 10 mg RAM for 22 weeks . The primary endpoint was change in trough , seated , clinic SBP .  Mean patient age was 57±11 years , 52.4 % were male , 99.5 % were Caucasian . Mean baseline BP was 161.1±7.9/94.9±9.0 mm Hg . Clinic SBP decreased by 20.6±0.95 and 21.2±0.95 mm Hg with AZL-M 40 and 80 mg vs12.2±0.95 mm Hg with RAM ( P<0.001 for both AZL-M doses ) . Adverse events leading to discontinuation were less frequent with AZL-M 40 and 80 mg ( 2.4 % and 3.1 % , respectively ) than with RAM ( 4.8 % ) . These data demonstrated that treatment of stage 1–2 hypertension with AZL-M was more effective than RAM and better tolerated Azilsartan medoxomil is an angiotensin receptor blocker ( ARB ) being developed for hypertension treatment . To compare this ARB with others in the class , we studied the effects of 2 doses of azilsartan medoxomil , with valsartan 320 mg and olmesartan medoxomil ( olmesartan ) 40 mg , in a r and omized , double-blind , placebo-controlled trial using ambulatory blood pressure ( BP ) monitoring and clinic BP measurements . The primary efficacy end point was the change from baseline in 24-hour mean systolic BP . Hierarchical analysis testing for superiority over placebo was followed by noninferiority analysis and then superiority testing of azilsartan medoxomil ( 80 mg and then 40 mg ) versus the comparator ARBs . For 1291 r and omized patients , mean age was 56 years , 54 % were men , and baseline 24-hour mean systolic BP was 145 mm Hg .  Azilsartan medoxomil at 80 mg had superior efficacy to both valsartan at 320 mg and olmesartan at 40 mg : placebo-adjusted 24-hour systolic BP was lowered ( −14.3 mm Hg ) more than 320 mg of valsartan ( −10.0 mm Hg ; P<0.001 
    Output:
    
Results : AZL-M was found to be more effective in terms of reducing indices of blood pressure over alternative ARBs or angiotensin-converting enzyme ( ACE ) inhibitors with minimal side effects .
Pre clinical studies have established pleiotropic effects for AZL-M beyond its primary antihypertensive role through differential gene expression , up-regulation of membrane receptors and favorable effect on selective intracellular biochemical and pro-atherosclerotic pathways .
Conclusion : Indirect but accumulating evidence from recent literature supports the efficacy and safety of AZL-M among diabetic patients .
However , no clinical data exist to date that evince a beneficial role of AZL-M in patients with metabolic disorders on top of its antihypertensive effect .