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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The mechanism of action, pharmacokinetics, pharmacodynamics, clinical efficacy, and adverse effects of candesartan cilexetil are reviewed. Candesartan is an angiotensin II-receptor blocker (ARB). It is administered as a pro-drug that undergoes activation during gastrointestinal absorption. The agent is excreted mostly unchanged and has a terminal half-life of about nine hours (slightly longer in the elderly). Candesartan differs from other agents in its class in that it is tightly bound to angiotensin II type 1 receptors, allowing prolonged activity. In clinical trials, candesartan cilexetil has produced a dose-dependent effect when given in dosages of 2-32 mg/day. Observed trough-to-peak blood pressure ratios support a once-daily dosage regimen. The antihypertensive effect of candesartan cilexetil 4-16 mg/day was as great as that of enalapril 10-20 mg/day and amlodipine 5 mg/day and larger than that of losartan potassium 50 mg/day. Adding candesartan cilexetil to hydrochlorothiazide 12.5-25 mg/day and amlodipine 5 mg/day led to enhanced blood-pressure reductions and was well tolerated. It appears that candesartan can decrease renal perfusion without adversely affecting renal blood flow and may mediate a decrease in albuminuria in hypertensive patients with type 2 diabetes. No clinically important drug interactions have been reported. Adverse effects include headache, dizziness, nausea, diarrhea, and transient elevations in liver transaminases. The frequency of cough is similar to that seen with placebo. Candesartan cilexetil is an effective antihypertensive agent that can be used alone or in combination with other antihypertensive drugs. It is generally well tolerated and may be an option for patients who cannot tolerate angiotensin-converting-enzyme inhibitors because of cough.
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PMID:Candesartan cilexetil: an angiotensin II-receptor blocker. 1078 59

The main objective of the CALM (Candesartan And Lisinopril Microalbuminuria) study is to assess the effect of a dual blockade of the renin-angiotensin system--using both an angiotensin converting enzyme inhibitor (ACE-I) and an angiotensin II type 1 receptor blocker--in patients with type 2 diabetes, high blood pressure and microalbuminuria. The study included 200 patients randomized to receive candesartan 16 mg or lisinopril 20 mg for 12 weeks, followed by 12 weeks of the same monotherapy or a combination treatment. Main outcomes are the reduction of microalbuminuria and blood pressure. All three of the treatments are effective, but the dual blockade is respectively 18%, 8 mmHg and 5 mmHg more effective in reducing microalbuminuria, systolic and diastolic blood pressure. No comparison is made between this "new" association and the more frequently used biotherapy (i.e. ACE-I plus thiazidic diuretic) and therefore its usefulness in regular practice is still to be determined.
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PMID:[Clinical study of the month. The CALM study assessing the combination of an angiotensin-converting enzyme inhibitor and an angiotensin II receptor antagonist in the treatment of diabetic nephropathy]. 1129 48

Candesartan shows beneficial end-organ effects in the kidney. Some of these appear to be related not to the reduction in systemic blood pressure induced by candesartan, but to its blockage of intrarenal angiotensin II type I (AT1) receptors. Initial studies have shown that renal vascular resistance was reduced in patients with hypertension receiving candesartan, and urinary albumin excretion was reduced in patients with type 2 diabetes mellitus and concomitant microalbuminuria or proteinuria. These findings, together with the results of recently published large randomized studies involving diabetic patients with hypertension treated with other angiotensin II receptor blockers, indicate that this class of drugs is beneficial in preventing the development or progression of diabetic nephropathy. This review summarizes the large body of findings related to these renoprotective effects and reported during experimental and clinical research on candesartan for the treatment of diabetic nephropathy.
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PMID:Candesartan: nephroprotective effects and treatment of diabetic nephropathy. 1294 96

Hypertension continues to be a major public health issue in the world. To combat this problem, many anti-hypertensive drugs have been developed and proven effective at controlling blood pressure in the last half century. In recent decades, antihypertensive drugs have been shown to have cardiovascular benefits beyond the reduction of blood pressure, and the focus has shifted to clarification of these effects. Angiotensin II receptor antagonists and calcium channel blockers are the most widely used antihypertensive drugs in Japan. However, these two classes of drugs have not yet been compared with respect to their efficacy for treating cardiovascular events. The Candesartan Antihypertensive Survival Evaluation in Japan (CASE-J) trial described herein is a prospective, multicenter, randomized, open-label, active-controlled, 2-arm parallel group comparison with a response-dependent dose titration and blinded assessment of endpoints in high-risk hypertensive patients treated with either an angiotensin II receptor antagonist (candesartan cilexetil) or a third-generation calcium channel blocker (amlodipine besilate). The eligibility criteria in this study were 1) age between 20 and 85 years; 2) systolic blood pressure (SBP) > or = 140 mmHg in those below 70 years of age or > or = 160 mmHg in those above 70 years of age or diastolic blood pressure (DBP) > or = 90 mmHg on two consecutive measurements at clinic; and 3) at least one of the following high risk factors for cardiovascular events: a) SBP > or = 2180 mmHg or DBP > or = 110 mmHg on two consecutive visits, b) type 2 diabetes mellitus (fasting blood glucose > or = 126 mg/dl, casual blood glucose > or = 200 mg/dl, HbA1c > or = 6.5%, 2 h blood glucose on 75 g oral glucose tolerance test (OGTT) > or = 200 mg/dl, or current treatment with hypoglycemic therapy), c) history of cerebral hemorrhage, cerebral infarction, or transient ischemic attack until 6 months prior to the screening, d) left ventricular hypertrophy on either echocardiography or ECG, angina pectoris, or history of myocardial infarction until 6 months prior to screening, e) proteinuria or serum creatinine > or = 1.3 mg/dl, and f) symptoms of arteriosclerotic artery obstruction. The therapeutic goals of blood pressure control were set as follows: SBP < 130 mmHg and DBP < 85 mmHg for patients below 60 years of age, SBP < 140 mmHg and DBP < 90 mmHg for those in their 60s, SBP < 150 mmHg and DBP < 90 mmHg for those in their 70s, and SBP < 160 mmHg and DBP < 90 mmHg for those in their 80s. A total of 3,200 patients, equally allocated to each of the two treatment arms, were required based on a two-sided alpha level 0.05 and 90% power. The CASE-J is also the first study to employ the newly developed Automatic Bar Code Data-Capturing/Allocation, Booking & Trial Coding, Data Management (ABCD) system for data collection and management. Enrollment of patients started in September 2001 and ended in December 2002. Follow-up data will be collected every 6 months until December 2005. The CASE-J trial will provide important evidence on the comparative effectiveness of candesartan cilexetil and amlodipine besilate on cardiovascular morbidity and mortality among Japanese. In addition, the use of the ABCD system is expected to contribute to the development of more efficient data management systems for large-scale clinical trials.
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PMID:Candesartan Antihypertensive Survival Evaluation in Japan (CASE-J) trial of cardiovascular events in high-risk hypertensive patients: rationale, design, and methods. 1471 41

Decreased left ventricular long-axis function may be the earliest stage in subclinical heart failure in Type II diabetes. To assess whether a decrease in SBP (systolic blood pressure) or a change in metabolic control would improve the long-axis function, 48 Type II diabetic patients participating in the CALM II (Candesartan and Lisinopril Microalbuminuria II) study were included in the present study. Patients were examined with tissue Doppler echocardiography at baseline and after 3 and 12 months of follow-up. Corresponding blood pressure, fructosamine and HbA(1c) (glycated haemoglobin) values were obtained. During the follow-up period, a decrease in SBP of 8 mmHg was seen (from 141+/-11 mmHg at baseline to 133+/-12 mmHg; P<0.001) and the peak systolic strain rate was significantly improved (from -1.10+/-0.25 at baseline to -1.25+/-0.22; P<0.01). There was a highly significant relationship between the changes in systolic strain rate, HbA(1c) (P<0.001) and fructosamine (P<0.05), and similarly to changes in left ventricular mass (P<0.05), whereas the correlation to the SBP reduction was not significant. Patients with improved glycaemic control, defined as a reduced HbA(1c) value after 12 months of follow-up, had a significantly improved strain rate (from -1.07+/-0.3 s(-1) at baseline to -1.32+/-0.25 s(-1); P<0.01) compared with patients with increases in HbA(1c) (from -1.14+/-0.25 s(-1) at baseline to -1.16+/-0.27 s(-1); P=not significant). The two groups had comparable baseline values of SBP, left ventricular mass, age and disease duration. In conclusion, changes in left ventricular systolic long-axis function are significantly correlated with changes in left ventricular mass, as well as metabolic control, in hypertensive patients with Type II diabetes mellitus.
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PMID:Effects of blood pressure lowering and metabolic control on systolic left ventricular function in Type II diabetes mellitus. 1651 87

We examined the effects of the angiotensin-II receptor antagonist candesartan on non-alcoholic fatty liver (NAFL) and circulating adiponectin concentrations in KKAy obese mice with type 2 diabetes mellitus. The KKAy mice were randomly assigned to receive either candesartan at a once-daily dose of 10 mg/kg (n = 5) or placebo (n = 5). The differences in liver weight, histological evaluation of hepatic lipid infiltration, serum adiponectin concentration and hepatic adiponectin mRNA levels between the two groups were determined on day 7 after treatment was initiated. Candesartan-treated mice demonstrated significantly lower liver weights and reduced lipid droplets in hepatic cells compared with control mice. The circulating adiponectin levels and hepatic expression of adiponectin mRNA were significantly higher in candesartan-treated mice than control mice. These results suggest that candesartan might alleviate NAFL through elevation of circulating adiponectin levels in KKAy obese mice with type 2 diabetes mellitus.
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PMID:Angiotensin-II receptor antagonist alleviates non-alcoholic fatty liver in KKAy obese mice with type 2 diabetes. 1686 24

Type 2 diabetes often occurs in association with hypertension and cardiovascular disease, and markedly increases cardiovascular risk. Strategies to reduce the incidence of diabetes in patients with cardiovascular disease or at high risk for such disease are therefore important. Certain classes of antihypertensive agents, namely the thiazide diuretics and beta-blockers, have an adverse impact on the metabolic profile and increase the risk for new-onset diabetes in hypertensive subjects. In contrast, angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs), which are blockers of the renin-angiotensin system (RAS), have been shown to increase insulin sensitivity. They may also reduce the risk of diabetes in patients with hypertension or cardiovascular disorders. Some of the evidence in favour of ACE inhibitors and ARBs has come from studies with active comparators that have potential adverse metabolic effects. However, the Candesartan in Heart failure-Assessment of Reduction in Mortality and morbidity (CHARM) programme demonstrated that the ARB candesartan reduced the incidence of diabetes in heart failure patients in comparison to placebo. The mechanisms responsible for the beneficial effects of RAS blockade remain to be established. Nevertheless, a treatment that can control hypertension and reduce the risk of onset of type 2 diabetes at the same time is certainly desirable.
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PMID:Renin-angiotensin-system blockade in the prevention of diabetes. 1732 Sep 99

Retinopathy is the most common microvascular complication of diabetes mellitus, and is an important cause of blindness worldwide. Clinical trials have demonstrated that tight metabolic control inhibits the progression of retinopathy. Good blood pressure control has been shown to be protective in type 2 diabetes, and it may also reduce proliferative retinopathy in type 1 diabetes. However, such control is often difficult to achieve in clinical practice, and may be associated with problems such as hypoglycaemia. New therapies are therefore needed to reduce the risk of retinopathy. There is growing evidence that the renin-angiotensin system (RAS) plays an important role in the pathogenesis of diabetic retinopathy, and this has led to interest in RAS inhibitors as agents to prevent retinopathy. Several trials have suggested that ACE inhibitor therapy can inhibit progression of retinopathy. The Diabetic Retinopathy Candesartan Trials (DIRECT) Programme is currently investigating the effects of the angiotensin II receptor blocker candesartan on the incidence of retinopathy in type 1 diabetes and its progression in type 1 and type 2 diabetes. It is hoped that the results from such large-scale clinical trials will provide more specific information about the medical treatment of diabetic retinopathy.
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PMID:Prospects for angiotensin receptor blockers in diabetic retinopathy. 1732 27

Using the cardio-ankle vascular index (CAVI) as an indicator, we assessed improvement of arterial stiffness in 95 outpatients with hypertension complicated by type 2 diabetes mellitus who were treated orally for >or= 12 months with telmisartan 40 mg/day, losartan 50 mg/day or candesartan 8 mg/day. At 1 year, in the telmisartan and losartan groups CAVI did not change whereas in the candesartan group CAVI showed a statistically significant decrease of 2.70%. Although telmisartan is believed to enhance the activity of peroxisome proliferator-activated receptor (PPAR-gamma) in vitro, it did not ameliorate arterial stiffness in our patients. Candesartan, however, improved arterial stiffness independently of blood pressure lowering and without PPAR-gamma agonist action, possibly by direct action resulting from its potent affinity and binding capacity for the angiotensin II type 1 receptor. We conclude that candesartan is a potentially useful therapy against arterial stiffness in hypertensive patients with type 2 diabetes mellitus.
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PMID:Relative effects of telmisartan, candesartan and losartan on alleviating arterial stiffness in patients with hypertension complicated by diabetes mellitus: an evaluation using the cardio-ankle vascular index (CAVI). 1883 6

Treatment with angiotensin II receptor blockers is associated with lower risk for the development of type 2 diabetes mellitus compared with thiazide diuretics. The Mechanisms for the Diabetes Preventing Effect of Candesartan Study addressed insulin action and secretion and body fat distribution after treatment with candesartan, hydrochlorothiazide, and placebo. Twenty-six nondiabetic, abdominally obese, hypertensive patients were included in a multicenter 3-way crossover trial, and 22 completers (by predefined criteria; 10 men and 12 women) were included in the analyses. They underwent 12-week treatment periods with candesartan (C; 16 to 32 mg), hydrochlorothiazide (H; 25 to 50 mg), and placebo (P), respectively, and the treatment order was randomly assigned and double blinded. Intravenous glucose tolerance tests and euglycemic hyperinsulinemic (56 mU/m(2) per minute) clamps were performed. Intrahepatic and intramyocellular and extramyocellular lipid content and subcutaneous and visceral abdominal adipose tissue were measured using proton magnetic resonance spectroscopy and MRI. Insulin sensitivity (M-value) was reduced following H versus C and P (6.07+/-2.05, 6.63+/-2.04, and 6.90+/-2.10 mg/kg of body weight per minute, mean+/-SD; P<or=0.01). Liver fat content was higher (P<0.05) following H than both P and C. The subcutaneous to visceral abdominal adipose tissue ratio was reduced following H versus C and P (P<0.01). Glycosylated hemoglobin, alanine aminotransferase, aspartate aminotransferase, and high-sensitivity C-reactive protein levels were higher (P<0.05) after H, but not C, versus P. There were no changes in body fat, intramyocellular lipid, extramyocellular lipid, or first-phase insulin secretion. Blood pressure was reduced similarly by C and H versus P. In conclusion, visceral fat redistribution, liver fat accumulation, low-grade inflammation, and aggravated insulin resistance were demonstrated after hydrochlorothiazide but not candesartan treatment. These findings can partly explain the diabetogenic potential of thiazides.
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PMID:Hydrochlorothiazide, but not Candesartan, aggravates insulin resistance and causes visceral and hepatic fat accumulation: the mechanisms for the diabetes preventing effect of Candesartan (MEDICA) Study. 1925 58


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