Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hypertension is a powerful risk factor for cardiovascular (CV) morbidity and mortality; therefore, blood pressure (BP) lowering plays a central role in reducing the cardiovascular complications of hypertension, including stroke. Recent outcomes studies--Losartan Intervention For Endpoint reduction in hypertension, Reduction of Endpoints in Non-insulin-dependent Diabetes Mellitus with the Angiotensin II Antagonist Losartan, and the Irbesartan Type 2 Diabetic Nephropathy Trial--suggest that some angiotensin II antagonists are associated with CV and renal effects beyond their ability to lower BP in patients with hypertension or diabetic nephropathy and may play a role in the prevention of new-onset type 2 diabetes. Angiotensin II antagonists are associated with a wide variety of vascular, cardiac, and renal effects, as well as molecule-specific effects independent of those induced by the angiotensin-I receptor. These actions may offer a mechanistic explanation for the outcome benefits observed in patients with hypertension or diabetic nephropathy. Angiotensin-converting enzyme inhibitors and calcium-channel blockers may also have effects that are not completely explained by differences in the antihypertensive response to these agents, but the evidence is less robust. Collectively, these findings suggest that management of patients with hypertension, with or without diabetes or renal disease, should no longer be viewed as simply a matter of correcting elevated BP. Antihypertensive agents that possess CV benefits beyond their BP-reducing effects should be used to prevent the development of end-organ damage.
 ...
PMID:Do angiotensin II antagonists provide benefits beyond blood pressure reduction? 1602 Apr 2

Elevated arterial pressure is a major risk factor for progression to ESRD in diabetic nephropathy. However, the component of arterial pressure and level of BP control for optimal renal outcomes are disputed. Data from 1590 hypertensive patients with type 2 diabetes in the Irbesartan Diabetic Nephropathy Trial (IDNT), a randomized, double-blind, placebo-controlled trial performed in 209 clinics worldwide, were examined, and the effects of baseline and mean follow-up systolic BP (SBP) and diastolic BP and the interaction of assigned study medications (irbesartan, amlodipine, and placebo) on progressive renal failure and all-cause mortality were assessed. Other antihypertensive agents were added to achieve predetermined BP goals. Entry criteria included elevated baseline serum creatinine concentration up to 266 micromol/L (3.0 mg/dl) and urine protein excretion >900 mg/d. Baseline BP averaged 159/87 +/- 20/11 mmHg. Median patient follow-up was 2.6 yr. Follow-up achieved SBP most strongly predicted renal outcomes. SBP >149 mmHg was associated with a 2.2-fold increase in the risk for doubling serum creatinine or ESRD compared with SBP <134 mmHg. Progressive lowering of SBP to 120 mmHg was associated with improved renal and patient survival, an effect independent of baseline renal function. Below this threshold, all-cause mortality increased. An additional renoprotective effect of irbesartan, independent of achieved SBP, was observed down to 120 mmHg. There was no correlation between diastolic BP and renal outcomes. We recommend a SBP target between 120 and 130 mmHg, in conjunction with blockade of the renin-angiotensin system, in patients with type 2 diabetic nephropathy.
 ...
PMID:Independent and additive impact of blood pressure control and angiotensin II receptor blockade on renal outcomes in the irbesartan diabetic nephropathy trial: clinical implications and limitations. 1612 Aug 23

Proteinuria is a graded marker for kidney damage, as well as the risk for future cardiovascular events. Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin-receptor blockers (ARBs) reduce urinary protein excretion and slow progression of renal impairment, independent of blood pressure lowering. Both the Irbesartan Diabetic Nephropathy Trial (IDNT) and the Reduction in Endpoints in NIDDM with the Angiotensin Antagonist Losartan (RENAAL) study were large, randomized, prospective studies in type 2 diabetic patients with proteinuria. There was no reduction in the incidence of myocardial infarction or stroke with the ARBs compared to placebo in either trial. A broader overview of clinical trials comparing ACEIs and ARBs with other antihypertensive drugs fails to show any substantive blood pressure-independent effects on stroke or myocardial infarction with these classes of drugs. Therefore, for cardiovascular end points (as opposed to renal end points), it may be more important that the blood pressure is reduced, rather than how the process is started.
 ...
PMID:Antihypertensive, antiproteinuric therapy and myocardial infarction and stroke prevention. 1615 81

There is a rising incidence and prevalence of ESRD as a result of diabetes, with poor outcome and growing costs. Recently, two large trials, the Irbesartan Diabetic Nephropathy Trial (IDNT) and Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan (RENAAL), showed that angiotensin receptor blockers (ARB) are more effective than traditional antihypertensive therapies at reducing progression toward ESRD in hypertensive patients with type 2 diabetes and overt nephropathy, regardless of changes in BP. The results of these two trials were used to compare the costs of ARB with those of renal replacement therapy (dialysis and renal transplantation) in an effort to establish whether ARB are cost-saving because they delay ESRD. Two different pharmacoeconomic approaches were used. With regard to the RENAAL trial, the number of ESRD days on losartan therapy as compared with the number of ESRD days on standard antihypertensive therapy was calculated, and the difference between the two was combined with the costs of ESRD. In the IDNT trial, Markov models were applied to assess the economic impact of irbesartan and to extrapolate future clinical and cost outcomes. Several economic analyses were performed in the United States and in European countries. Applying pharmacoeconomic models showed that treatment with ARB was associated with a greater improvement in life expectancy and lower total costs compared with amlodipine and standard antihypertensive therapy. Therefore, treating patients with type 2 diabetes, nephropathy, and hypertension with ARB is life- and cost-saving compared with traditional antihypertensive therapy.
 ...
PMID:Economic evaluation of angiotensin receptor blockers in type 2 diabetes, hypertension, and nephropathy. 1656 46

Angiotensin II receptor antagonists (angiotensin II receptor blockers; ARBs) are a class of antihypertensive drugs that are generally considered comparable to ACE inhibitors in the prevention of heart and kidney failure. However, these two classes of agents do interfere in different stages of the renin-angiotensin system. In patients with type 2 diabetes mellitus, advantages for ARBs over conventional (non-ACE inhibitor) therapy on progression from micro- to macroalbuminuria and overt nephropathy and end-stage renal disease have been shown in clinical trials. In patients with type 2 diabetes and end-stage renal disease, the need for dialysis and/or transplantation results in the use of major healthcare resources. This paper reviews the available economic evidence on treatment with ARBs in type 2 diabetic patients with advanced renal disease.Within-trial analytic and Markov model economic evaluations of the RENAAL (Reduction of Endpoint in Non-insulin dependent diabetes mellitus with Angiotensin II Antagonist Losartan), IDNT (Irbesartan Diabetic Nephropathy Trial) and IRMA (IRbesartan in type 2 diabetes with MicroAlbuminuria)-2 studies suggest that treatment with ARBs in patients with type 2 diabetes with overt or incipient nephropathy confers health gains and net cost savings compared with conventional (non-ACE inhibitor) therapy. For reimbursement and reference pricing decisions, there is a need for a head-to-head comparison of an ACE inhibitor with ARBs to model all possible costs and effects of ACE inhibitors and ARBs. This will result in a proper pharmacoeconomic outcome, where both types of drugs can be compared for healthcare decisions.
 ...
PMID:Pharmacoeconomics of angiotensin II antagonists in type 2 diabetic patients with nephropathy: implications for decision making. 1676 1

This subgroup analysis of the Irbesartan/Hydrochlorothiazide (HCTZ) Blood Pressure Reductions in Diverse Patient Populations (INCLUSIVE) trial evaluated the efficacy and safety of irbesartan/HCTZ fixed combinations in adults with uncontrolled systolic blood pressure (SBP) (140-159 mm Hg; 130-159 mm Hg for type 2 diabetes mellitus [T2DM]) after >or=4 weeks of antihypertensive monotherapy. Treatment was sequential: placebo (4-5 weeks), HCTZ 12.5 mg (2 weeks), irbesartan/HCTZ 150/12.5 mg (8 weeks), and irbesartan/HCTZ 300/25 mg (8 weeks). In the intent-to-treat analysis, mean change from baseline (end of placebo phase) off all previous therapy to Week 18 (study end) in T2DM patients (n=227) was -18.2+/-14.1 mm Hg for SBP (primary end point; p<0.001) and -8.7+/-8.2 mm Hg for diastolic blood pressure (p<0.001). Mean SBP/diastolic blood pressure changes in patients with the metabolic syndrome (n=345) were -21.0+/-14.3/-10.4+/-8.5 mm Hg (p<0.001). Overall, 56% (95% confidence interval, 49%-62%) of T2DM and 73% (95% confidence interval, 68%-77%) of metabolic syndrome patients achieved SBP goal (<140 mm Hg; <130 mm Hg for T2DM). Goal attainment rates were significantly higher among women with the metabolic syndrome than men. Treatments appeared to be well tolerated. Irbesartan/HCTZ fixed combinations achieved SBP goals in over half of the T2DM patients and nearly three quarters of patients with the metabolic syndrome, with SBP uncontrolled on antihypertensive monotherapy.
 ...
PMID:Antihypertensive efficacy of Irbesartan/HCTZ in men and women with the metabolic syndrome and type 2 diabetes. 1684

To perform a health economic analysis on treatment with irbesartan in patients with type 2 diabetes and hypertension. A Markov model was adapted to the Hungarian setting to simulate renal deterioration from the development of microalbuminuria to nephropathy, doubling of serum creatinine, end-stage renal disease (ESRD) and all-cause mortality. Outcomes for two treatments were evaluated: (1) a placebo regimen of standard antihypertensive medications, and (2) the addition of irbesartan 300 mg administered daily, with both treatment initiated after developing microalbuminuria. Outcomes were discounted at 5% annually to correspond with national guidelines. Treatment with irbesartan was estimated to improve undiscounted life expectancy by 0.98 +/- 0.05 years, reduce the cumulative incidence of ESRD by 7.5 +/- 0.4%, and reduce lifetime costs by Hungarian Forints (HUF) 519,993 +/- 70,814, compared to placebo. Irbesartan was projected to improved life expectancy and reduce costs compared to placebo in the Hungarian setting in hypertensive patients with type 2 diabetes and microalbuminuria.
 ...
PMID:Health economic implications of irbesartan treatment versus standard blood pressure control in patients with type 2 diabetes, hypertension and renal disease: a Hungarian analysis. 1723 27

The objective of the study was to determine the impact of irbesartan treatment on life expectancy (LE), costs and progression to end-stage renal disease (ESRD) in hypertensive type 2 diabetes patients. A peer-reviewed and published Markov model was used to simulate progression from microalbuminuria to overt nephropathy, doubling of serum creatinine, ESRD and all-cause mortality in hypertensive patients with type 2 diabetes. Three treatment strategies were evaluated: (i) 'control' regimen of conventional antihypertensive therapy (excluding angiotensin-converting enzyme inhibitors, angiotensin-2-receptor antagonists and dihydropyridine calcium-channel blockers), (ii) 'early irbesartan' 300 mg daily and (iii) 'late irbesartan' 300 mg daily (started when overt nephropathy developed). Transition probabilities determining nephropathy progression were taken from the Irbesartan in Reduction of Microalbuminuria-2 study, Irbesartan in Diabetic Nephropathy Trial and other published sources. Outcomes were projected over 25 years. The mean +/- SD cumulative incidence of ESRD was reduced by 8.8% +/- 0.6 and 12.4% +/- 0.7 in patients treated with early irbesartan compared with late irbesartan and control respectively. Early irbesartan treatment improved undiscounted LE by 1.38 +/- 0.08 years (discounted: 0.81 +/- 0.04 years) compared with late irbesartan and 1.41 +/- 0.08 years (discounted: 0.83 +/- 0.04 years) compared with control. Early irbesartan treatment was projected to save (mean +/- SD) pounds 2310 +/- 327 and pounds 3801 +/- 327 over patient lifetimes compared with late irbesartan and control respectively. Irbesartan treatment is predicted to improve survival and reduce costs in hypertensive patients with type 2 diabetes and microalbuminuria compared with 'control'. Early irbesartan treatment is more effective than late irbesartan. Irbesartan is a valuable treatment option in this patient group in a UK setting.
 ...
PMID:Irbesartan treatment of patients with type 2 diabetes, hypertension and renal disease: a UK health economics analysis. 1787 49

A post hoc pooled analysis of 2 multicenter, randomized, double-blind, active-controlled force-titration studies assessed the antihypertensive efficacy and tolerability of 7 to 8 weeks' once-daily fixed-dose irbesartan/hydrochlorothiazide (HCTZ) 300/25 mg in 796 stage 1 or 2 hypertensive patients according to age (65 years or older or younger than 65) (n=121 or 675) and presence or absence of obesity (n=378 or 414), type 2 diabetes (n=99 or 697), and high World Health Organization-defined cardiovascular risk (n=593 or 202). Systolic/diastolic blood pressure reductions (27-31/16-22 mm Hg) were similar regardless of age, obesity, and type 2 diabetes status and were greater in high- vs low-risk patients. Dizziness (2.0%-3.7%), hypotension (0%-0.7%), and syncope (0%) were rare and not centered in any subgroup. There was no hypotension in the elderly or in type 2 diabetics. Irbesartan/HCTZ provided consistent blood pressure lowering and tolerability regardless of age, obesity, and type 2 diabetes and greater efficacy in patients with high cardiovascular risk.
 ...
PMID:The efficacy and safety of initial use of irbesartan/hydrochlorothiazide fixed-dose combination in hypertensive patients with and without high cardiovascular risk. 1804 9

The secondary analysis of the Irbesartan/Hydrochlorothiazide Blood Pressure Reductions in Diverse Patient Populations (INCLUSIVE) clinical trial investigated whether baseline demographic and clinical variables are predictive of different degrees of blood pressure reduction following an angiotensin II receptor blocker/diuretic treatment regimen. Irbesartan/hydrochlorothiazide and other angiotensin receptor blocker combinations with a diuretic have been shown to be effective in reducing systolic blood pressure in a diverse patient population previously uncontrolled on monotherapy. Ordinary least squares regression analysis was performed on the intent-to-treat population of the INCLUSIVE study to identify variables predictive of variations in blood pressure changes in response to irbesartan/hydrochlorothiazide combination therapy. Higher baseline systolic blood pressure, female sex, type 2 diabetes, and statin therapy were found to be predictive of additional blood pressure lowering with this combination. The impact of higher baseline systolic blood pressure and diabetic state on changes in systolic blood pressure were diminished in female patients compared with male patients. In conclusion, a significant correlation may exist between certain clinical/demographic characteristics and the extent of the therapeutic response with irbesartan/hydrochlorothiazide treatment.
 ...
PMID:Predictors of blood pressure response to angiotensin receptor blocker/diuretic combination therapy: a secondary analysis of the irbesartan/hydrochlorothiazide blood pressure reductions in diverse patient populations (INCLUSIVE) study. 1817 68


<< Previous 1 2 3 4 5 Next >>