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Oral Hypoglycaemic Agents (oral + hypoglycaemic_agent)

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Medical Sciences	94%

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Combination therapy with sulfonylureas and metformin and the prevention of death in type 2 diabetes: a nested case-control study,

PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 4 2010
Laurent Azoulay PhD
Abstract Purpose To determine whether combination of sulfonylureas and metformin increases the risk of death from any cause in patients with type 2 diabetes. Methods A nested case-control study was conducted within a population-based cohort from the UK General Practice Research Database (GPRD). The cohort included patients over the age of 40 who were prescribed a first oral hypoglycaemic agent between 1 January 1988 and 30 June 2008. Cases included all patients who deceased during follow-up. Up to 10 controls were matched to each case on year of birth, date of cohort entry (±1 year) and duration of follow-up. Conditional logistic regression was used to estimate rate ratios (RRs) of death from any cause associated with the use of combination of sulfonylureas and metformin, relative to sulfonylurea monotherapy. Results The cohort comprised 84,231 users of oral hypoglycaemic agents, of whom 14,996 died from any cause during a mean of 4.3 years of follow-up (mortality rate 4.1 per 100 per year). Patients currently exposed to a combination of sulfonylureas and metformin were at a decreased risk of death from any cause compared to patients exposed to sulfonylurea monotherapy (adjusted RR: 0.77, 95%CI: 0.70, 0.85). Similar results were obtained for patients currently exposed to metformin monotherapy (adjusted RR: 0.70, 95%CI: 0.64, 0.75) when compared to sulfonylurea monotherapy. Patients had to be exposed to the combination therapy for at least 4 months prior to index date to experience a lower risk of mortality compared to sulfonylurea monotherapy. Conclusions The combination of sulfonylureas and metformin does not increase the risk of death. In contrast, it may moderately reduce this risk compared to sulfonylurea monotherapy. Copyright © 2010 John Wiley & Sons, Ltd. [source]

The glucose lowering effect of an oral insulin (Capsulin) during an isoglycaemic clamp study in persons with type 2 diabetes

DIABETES OBESITY & METABOLISM, Issue 1 2010
S. D. Luzio
Aim: Randomized, open, single-centre, two-way crossover study comparing the pharmacokinetic (PK) and pharmacodynamic (PD) properties of subcutaneous (sc) regular human insulin (Actrapid) and oral insulin in a capsule form (Capsulin). Methods: Sixteen persons (12 males) with type 2 diabetes on oral hypoglycaemic agents (OHAs) participated. Mean (s.d.) age 60.2 (5.5) years, BMI 28.3 (3.4) kg/m2, haemoglobin A1c (HbA1c) 7.4% (1.1). Two 6-h isoglycaemic glucose clamp studies were conducted 11 days apart. All subjects received in random order 12U sc Actrapid on one clamp study day and either 150U or 300U Capsulin (Cap) on the other day. Glucose infusion rates (GIRs), plasma insulin and C-peptide concentrations were determined throughout each 6-h isoglycaemic clamp. Between the clamp study days, all patients received 150U Capsulin twice daily, dropping all their standard OHAs apart from metformin. Self-monitored blood glucose (SMBG) levels were taken four times a day between the clamp study days. Results: Administration of either Actrapid or Capsulin (150 and 300U) increased GIRs reaching a maximum values at approximately 280,330 min. Overall values for maximum GIR values were higher for Actrapid than either dose of Capsulin (p < 0.05). The significantly greater systemic insulin concentrations following Actrapid were reflected in the AUC0,6 h (910 ± 270 vs. 472 ± 245 pmol h/L; 950 ± 446 vs. 433 ± 218 pmol h/L; both p < 0.05 for Actrapid vs. 150U Capsulin and 300U Capsulin respectively). No difference was observed between 150U and 300U Capsulin. During the repeat-dosing period, good safety and tolerability were observed with Capsulin, and SMBG levels remained stable. At the poststudy visit, significant falls in HbA1c, weight and triglycerides were observed. Conclusions: Administration of the oral insulin Capsulin preparation demonstrated a significant hypoglycaemic action over a period of 6 h associated with only a small increase in circulating plasma insulin concentrations. [source]

Twice daily biphasic insulin aspart improves postprandial glycaemic control more effectively than twice daily NPH insulin, with low risk of hypoglycaemia, in patients with type 2 diabetes

DIABETES OBESITY & METABOLISM, Issue 6 2003
J. S. Christiansen
Objective:, Biphasic insulin aspart 30 (BIAsp30) is a dual release formulation, containing 30% soluble and 70% protamine-crystallized insulin aspart. This study compared the glycaemic control and safety profiles achieved with either twice daily BIAsp30 or NPH insulin in patients with type 2 diabetes not optimally controlled by oral hypoglycaemic agents (OHAs), NPH insulin or a combination of both. Methods:, In this 16-week multinational, parallel-group, double-blind trial, 403 such patients were randomized to receive either BIAsp30 or NPH insulin immediately before breakfast and evening meals. OHAs were discontinued at randomization. Efficacy was assessed by glycosylated haemoglobin (HbA1c) and self-recorded daily 8-point blood glucose (BG) profiles. Hypoglycaemic and other adverse events were the chosen safety parameters. Results:, HbA1c concentration decreased by >0.6% (p < 0.0001 vs. baseline) in both groups, with metabolic control continuing to improve throughout the trial without reaching a stable level. Patients who switched from once or twice daily NPH monotherapy to twice daily BIAsp30 achieved a significantly greater reduction in HbA1c (0.78%) than those randomized to twice daily NPH insulin (0.58%; p = 0.03). BIAsp30 decreased mean daily postprandial glycaemic exposure to a greater extent than NPH insulin (mean difference = 0.69 mmol/l; p < 0.0001), reflecting greater decreases in the postbreakfast and postdinner increments (of 1.26 and 1.33 mmol/l, respectively), although postlunch increment was relatively increased (by 0.56 mmol/l). Despite the greater reduction in overall postprandial glycaemic exposure in the BIAsp30 group, the overall safety profile of BIAsp30 was equivalent to that of NPH insulin with <2% of patients experiencing major hypoglycaemia, and approximately 33% reporting minor hypoglycaemic episodes, in both groups. Conclusion:, Twice daily BIAsp30 reduced postprandial glucose exposure to a significantly greater extent than NPH insulin and was at least as effective at reducing HbA1c in patients with type 2 diabetes. Both insulins were well tolerated. In patients poorly controlled on OHAs or NPH alone, glycaemic control can be improved by switching to twice daily BIAsp30, without increasing hypoglycaemic risk. [source]

Self glucose monitoring and physical exercise in diabetes

DIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue S1 2009
G. Pugliese
Abstract Cardiorespiratory fitness, which is determined mainly by the level of physical activity, is inversely related to mortality in the general population as well as in subjects with diabetes, the incidence of which is also increased by low exercise capacity. Exercise is capable of promoting glucose utilization in normal subjects as well as in insulin-deficient or insulin-resistant diabetic individuals. In diabetic subjects treated with insulin or insulin secretagogues, exercise may also result in complications, with too much insulin causing hypoglycaemia and not enough insulin leading to hyperglycaemia and possibly ketoacidosis; both complications may also occur several hours after exercise. Therefore, self-monitoring of blood glucose before, during (for exercise duration of more than 1 h) and after physical exercise is highly recommended, and also carbohydrate supplementation may be required. In the Italian Diabetes Exercise Study (IDES), measurement of blood glucose and systolic and diastolic blood pressure levels before and after supervised sessions of combined (aerobic + resistance) exercise in type 2 diabetic subjects with the metabolic syndrome showed significant reductions of these parameters, though no major hypoglycaemic or hypotensive episode was detected. The extent of reduction of blood glucose was related to baseline values but not to energy expenditure and was higher in subjects treated with insulin than in those on diet or oral hypoglycaemic agents (OHA). Thus, supervised exercise training associated with blood glucose monitoring is an effective and safe intervention to decrease blood glucose levels in type 2 diabetic subjects. Copyright © 2009 John Wiley & Sons, Ltd. [source]

Self-monitoring of blood glucose in type-2 diabetes: what is the evidence?

DIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 6 2007
Grace McGeoch
Abstract Background There is a controversy about self-monitoring of blood glucose (SMBG) in patients with type 2 diabetes who are not using insulin. Randomized trials are limited in duration, size, and validity. Methods Systematic search for randomized trials and observational studies published since 1990. For inclusion studies had to report on SMBG in type 2 diabetes managed with oral hypoglycaemic agents and/or diet alone, HbA1c or clinical outcome, have at least 50 patients and be of at least 6 months' duration. Results Three randomized trials with 1000 patients were included, though all had interventions differing in the amount of education on SMBG, and in the population studied. The two larger studies had statistically significantly lower HbA1c levels with SMBG. Thirteen observational studies had information on over 60 000 patients. Smaller studies had lower initial HbA1c and showed no association between SMBG and laboratory or clinical improvement. Larger studies tended to have higher initial HbA1c and did show an association between SMBG and laboratory or clinical improvement. Overall, improvement in glycaemic control with SMBG tended to be seen in studies with initial HbA1c above 8%. Conclusions It is likely that SMBG is beneficial in some circumstances, for example as an educational tool, for patients with type 2 diabetes not using insulin who have poor glycaemic control. More information is needed at the level of the individual patient, rather than group means, and about timing and frequency of monitoring, response to those results, what constitutes effective patient education, and long-term clinical outcomes. Copyright © 2007 John Wiley & Sons, Ltd. [source]

Assessing diabetic control , reliability of methods available in resource poor settings

DIABETIC MEDICINE, Issue 3 2002
A. P. Rotchford
Abstract Aims and methods To examine the reliability of random venous or capillary blood glucose testing, random urine glucose testing, and a current symptom history in predicting a high HbA1c in Type 2 diabetic patients taking oral hypoglycaemic agents in a poorly controlled rural African population. Results For a cut-off point for HbA1c of , 8%, for random venous plasma glucose of , 14 mmol/L (present in 47.2% of subjects), specificity was 97.1% (95% CI 85.1,99.9), sensitivity 56.8% (48.8,64.5) and positive predictive value (PPV) 98.9% (94.2,99.9). HbA1c, 8% is predicted by a random capillary blood glucose of 17 mmol/L (present in 28.4% of subjects) with specificity 100% (90.0,100.0), PPV 100% (93.7,100.0) and sensitivity of 34.3% (27.2,42.1). HbA1c, 8% is predicted by the presence of heavy glycosuria (, 55 mmol/L) (present in 35.6%) with specificity 94.1% (80.3,99.3), sensitivity of 41.9% (34.1,49.9) and PPV 97.1% (89.9,99.6). Polyuria/nocturia (present in 31.3%) was the only symptom found to be associated with poor control, with a specificity for predicting HbA1c of , 8% of 81.5% (61.9,93.7), PPV 89.1% (76.4,96.4) and sensitivity 30.6% (22.9,39.1). Conclusions Where resources are short, random glucose testing can be used to detect a significant proportion of those with the worst control with a high degree of specificity enabling primary care staff to modify treatment safely. Where facilities are limited capillary blood or urine testing with reagent strips, may be substituted for venous plasma testing in the laboratory. A symptom history was insufficient to replace biochemical testing, but where this is unavailable, urinary symptoms may be helpful. Diabet. Med. 19, 195,200 (2002) [source]

Beta-cell function evaluated by HOMA as a predictor of secondary sulphonylurea failure in Type 2 diabetes

DIABETIC MEDICINE, Issue 7 2001
M. J Taverna
Abstract Background and aims Secondary failure to oral hypoglycaemic agents, a common evolution of long-standing Type 2 diabetes, is usually assessed by non-standardized indices requiring fine clinical assessment, including hyperglycaemia resistant to maximum doses of sulphonylureas despite appropriate diet and follow-up. The goal of this study was to evaluate if HOMA, a modelized plasma insulin/glucose ratio allowing simple evaluation of residual insulin secretion and sensitivity, is a better predictor of the insulin requiring stage than clinical indices. Materials and methods HOMA was measured in 84 Type 2 diabetic patients aged 58 ± sd 6 years, with diabetes duration 11 ± 4 years, hospitalized because of hyperglycaemia resistant to maximal doses of sulphonylureas (e.g. glibenclamide ,,15 mg/day), with no apparent external reason for hyperglycaemia. Despite reinforced appropriate diet recommendations, 62 of these patients remained hyperglycaemic (insulin-requiring group). Results Age, duration of diabetes, body mass index (BMI) and HOMA value for insulin sensitivity (71 ± 6% vs. 76 ± 7%, normal values 59,161%) were comparable in the two groups. HbA1c was higher (10.0 ± 0.2% vs. 8.3 ± 0.3%, P < 0.001) and HOMA insulin secretion values lower (25 ± 2% vs. 43 ± 6%, normal values 70,150%, P < 0.01) in the insulin-requiring group. Of the following potential predictors: HbA1c >,8%, duration of diabetes ,,10 years, HbA1c combined with diabetes duration, insulin sensitivity ,,40%, insulin secretion ,,20%, the latter showed the best positive predictivity (86% patients with low insulin secretion were insulin-requiring). Conclusions (i) HOMA is a simple and good predictor of the insulin-requiring stage in Type 2 diabetes mellitus; (ii) this stage of diabetes is characterized by a further decline of insulin secretion rather than of insulin sensitivity. Diabet. Med. 18, 584,588 (2001) [source]

Comparison between repaglinide and glipizide in Type 2 diabetes mellitus: a 1-year multicentre study

DIABETIC MEDICINE, Issue 5 2001
S. Madsbad
Abstract Aims To evaluate the long-term effectiveness and safety of repaglinide, a novel prandial glucose regulator, in comparison with glipizide in the treatment of patients with Type 2 diabetes. Methods Diet or tablet-treated patients with Type 2 diabetes (n = 256; age 40,75 years, body mass index (BMI) 20,35 kg/m2, HbA1c 4.2,12.8%), without signs of severe microvascular or macrovascular complications, were included in this double-blind, multicentre, parallel-group comparative trial. Patients were randomized at a 2:1 ratio to repaglinide, 1,4 mg at mealtimes, or glipizide, 5,15 mg daily. Results Changes in fasting blood glucose (FBG) and HbA1c during the 12 months of treatment showed a significant difference in favour of repaglinide. In oral hypoglycaemic agents (OHA)-naive patients, HbA1c decreased in the repaglinide and glipizide groups by 1.5% and 0.3%, respectively (P < 0.05 between groups). Fasting blood glucose decreased in the repaglinide group by 2.4 mmol/l and increased in the glipizide group by 1.0 mmol/l (P < 0.05 between groups). In the study population as a whole, repaglinide was able to maintain glycaemic control (HbA1c level) during the 1-year study period, whereas control deteriorated significantly with glipizide. Change in HbA1c from baseline was significantly better with repaglinide than with glipizide after 12 months (P < 0.05). In addition, FBG deteriorated significantly in the glipizide group compared with the repaglinide group (P < 0.05). No patients in either group experienced a major hypoglycaemic event; the number of patients experiencing minor hypoglycaemia was similar in the repaglinide and glipizide groups (15% and 19%, respectively). Conclusions Repaglinide, given as a prandial glucose regulator, is shown to be an effective and safe treatment of patients with Type 2 diabetes, and is better than glipizide in controlling HbA1c and FBG levels, overall, and in OHA-naive patients. Diabet. Med. 18, 395,401 (2001) [source]

Obesity and cardiovascular risk factors in type 2 diabetes: results from the Swedish National Diabetes Register

JOURNAL OF INTERNAL MEDICINE, Issue 3 2006
M. RIDDERSTRÅLE
Abstract. Objectives., To compare obese with normal and overweight type 2 diabetic patients regarding body mass index (BMI) and cardiovascular risk factors, and to analyse changes in weight versus risk factors. Design and setting., A cross-sectional study of 44 042 type 2 patients, and a 6-year prospective study of 4468 type 2 patients. Results., Obese patients (BMI , 30 kg m,2), 37% of all patients, had high frequencies of hypertension (88%), hyperlipidaemia (81%) and microalbuminuria (29%). Only 11% had blood pressure <130/80 mmHg. Their ratio of triglycerides to HDL cholesterol was considerably elevated, whilst the mean total and LDL cholesterol were similar as in normal weight subjects. Obese patients had elevated odds ratios for hypertension, hyperlipidaemia and microalbuminuria: 2.1, 1.8 and 1.4 in the cross-sectional study, similarly confirmed in the prospective 6-year study. BMI was an independent predictor of these risk factors (P < 0.001), although only slightly associated with HbA1c and not with total or LDL cholesterol. A change in BMI during the prospective study was related to a change in HbA1c in patients treated with diet and oral hypoglycaemic agents (OHAs) but not with insulin. In all patients, an increase in BMI was related to the development of hypertension, and a change in BMI to change in blood pressure, also mostly confirmed when treated with diet, OHAs or insulin. Conclusions., The high frequencies of risk factors in obese type 2 patients implies an increased risk of cardiovascular disease and the need for therapeutic measures. The paradox that hypoglycaemic treatment accompanied by weight gain may increase cardiovascular risk factors seems to be verified here concerning hypertension but not concerning microalbuminuria. [source]

Medicinal plant species with potential antidiabetic properties

JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE, Issue 5 2007
Srinivasa Rao Mentreddy
Abstract Diabetes mellitus is one of the world's major diseases. It currently affects an estimated 143 million people worldwide and the number is growing rapidly. In the USA alone, about 20.8 million or 7% of the population suffer from diabetes or related complications. The estimated direct and indirect costs of diabetes exceed US$ 132 billion annually. Plant-based medicinal products have been known since ancient times, and several medicinal plants and their products (active natural principles and crude extracts) have been used to control diabetes in the traditional medicinal systems of many cultures worldwide, including those of the Asian Indians, Chinese and South Americans. A limited number of these plant species have been studied and validated for their hypoglycaemic properties using diabetic animal models and in clinical studies using human subjects. Several oral hypoglycaemic agents are the primary forms of treatment for diabetes. However, prominent side-effects of such drugs are the main reason for an increasing number of people seeking alternative therapies that may have less severe or no side-effects. Thus plant-based herbal drugs or botanicals are emerging as the primary components of holistic approaches to diabetes management. In this review, selected species that have been validated for their hypoglycaemic or antihyperglycaemic properties using laboratory diabetic animal models and in clinical trials using human subjects, and reported in refereed journals are presented. Copyright © 2007 Society of Chemical Industry [source]

Combination therapy with sulfonylureas and metformin and the prevention of death in type 2 diabetes: a nested case-control study,

The use of basal insulin (NPH) compared with pre-mixed biphasic insulin in patients with type 2 diabetes mellitus

PRACTICAL DIABETES INTERNATIONAL (INCORPORATING CARDIABETES), Issue 4 2007
A single centre experience
Abstract The aim of this retrospective study was to compare glycaemic control and weight gain in patients with type 2 diabetes (T2DM) commenced on basal insulin (BI) or mixed insulin (MI). Subjects had T2DM (mean duration seven years) poorly controlled while treated with oral hypoglycaemic agents. Two hundred patients (BI 131 [65%], MI 69 [35%], median age 60 years [range 30,97]) were investigated. Follow up was over a mean period of 3.8 years. Patients started on BI had a significantly lower HbA1c (mean 10.6% vs 11.1%, p = 0.007) and higher body mass index (31.8kg/m2vs 29.6, p = 0.005) compared to those on MI. At 3.5 years patients injecting BI were on a lower daily dose of insulin (BI 66.6units vs MI 99.1units, p = 0.02) and a higher proportion were taking metformin (88% vs 62%, p = 0.01). There was no significant difference in HbA1c (8.5% vs 8.4%, p = 0.36) at the end of follow up. At 2.5 years subjects injecting BI had less weight gain (BI mean 4.0kg vs MI mean 8.0kg, p = 0.02). At 3.5 years the difference in weight gain was not statistically significant (mean 5.0kg vs 7.8kg, p = 0.20). In our experience BI, used in combination with metformin, is an effective treatment option in patients with T2DM, maintains glycaemic control over long-term follow up and is associated with less weight gain than MI. Copyright © 2007 John Wiley & Sons. [source]

Combination treatment of insulin with oral hypoglycaemic agents in patients with type 2 diabetes mellitus

PRACTICAL DIABETES INTERNATIONAL (INCORPORATING CARDIABETES), Issue 8 2004
AN Dixon MRCP (UK) Clinical Research FellowArticle first published online: 7 DEC 200
Abstract The recently published guidelines from the National Institute for Clinical Excellence (NICE) on the management of blood glucose in type 2 diabetes and the NICE guidelines on the use of the long-acting insulin analogue, glargine, have brought to the fore the use of combination therapy of insulin with oral hypoglycaemic agents (OHAs). The NICE guidelines recommend that when a patient with type 2 diabetes is failing to achieve satisfactory glycaemic control with OHAs alone, insulin should be initiated in combination with OHAs. However, evidence for this approach is less than robust and combination treatment of OHAs with insulin remains a controversial area. This article presents the evidence for different insulin regimens in patients who have secondary failure to OHAs, including combination therapy with basal insulin. The evidence and potential drawbacks of such regimens are discussed. Copyright © 2004 John Wiley & Sons, Ltd. [source]

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PRESCRIBER, Issue 8 2008
Article first published online: 12 MAY 200
Glargine preferred to lispro as type 2 add-on Basal insulin glargine (Lantus) and insulin lispro (Humalog) at mealtimes improved glycaemic control equally well in patients with type 2 diabetes poorly controlled by oral agents, but patient satisfaction was greater with basal insulin (Lancet 2008;371:1073-84). The 44-week APOLLO trial, funded by Sanofi Aventis, was a nonblinded randomised comparison of basal and prandial insulin regimens added to oral treatment in 418 patients. It found similar reductions in HbA1C (,1.7 vs ,1.9 per cent respectively). Fasting and nocturnal glucose levels were lower with insulin glargine and postprandial levels were lower with insulin lispro. The basal regimen was associated with fewer hypoglycaemic events (5.2 vs 24 per patient per year), less weight gain (3.01 vs 3.54kg) and greater improvement in patient satisfaction scores. Treating hypertension cuts mortality in over-80s Treating hypertension in the over-80s reduces all-cause mortality by 21 per cent, the HYVET study has shown (N Engl J Med online: 31 March 2008; doi: 10.1056/NEJMoa 0801369). Compared with placebo, treatment with indapamide alone or with perindopril for an average of 1.8 years also reduced the incidence of fatal stroke by 39 per cent, cardiovascular death by 23 per cent and heart failure by 64 per cent. The incidence of stroke was reduced by 30 per cent but this was of borderline statistical significance. Fewer serious adverse events were reported with treatment than with placebo. New work for NICE The DoH has announced the 18th work programme for NICE. Seven public health interventions include preventing skin cancer, smoking by children and excess weight gain during pregnancy. Public health guidance will include the provision of contraceptive services for socially disadvantaged young people. Two new clinical guidelines are sedation in young people and management of fractured neck of femur. New technology appraisals may include eight therapies for cancer, two new monoclonal antibodies for psoriasis and rheumatoid arthritis, an oral retinoid for severe chronic hand eczema and methylnaltrexone for opioid-induced bowel dysfunction. Combinations no better against CV disease Taking ezetimibe and simvastatin (Inegy) does not appear to slow the progression of atherosclerosis more than high-dose simvastatin alone, say researchers from The Netherlands (N Engl J Med 2008;358: 1431-43). In patients with hypercholesterolaemia, there was no difference in regression or progression of atherosclerosis after two years' treatment with simvastatin 80mg per day alone or combined with ezetimibe 10mg per day. Adverse event rates were similar. In patients with vascular disease or high-risk diabetes, there was no difference between the ACE inhibitor ramipril 10mg per day or the ARB telmisartan (Micardis) 80mg per day as monotherapy, or their combination, in the risk of a composite outcome of cardiovascular death, MI, stroke and admission for heart failure (N Engl J Med 2008;358:1547-59). Combined treatment was associated with higher risks of hypotensive symptoms, syncope and renal dysfunction. Twice-daily celecoxib increases CV risk Taking celecoxib (Celebrex) twice daily carries a higher risk of cardiovascular events than the same total dose taken once daily, a metaanalysis suggests (Circulation 2008; doi: 10.1161/ CIRCULATIONAHA.108. 764530). The analysis of six placebo-controlled trials involving a total of 7950 patients taking celecoxib for indications other than rheumatoid arthritis found that the combined risk of cardiovascular death, myocardial infarction, stroke, heart failure or thromboembolic event increased with dose over the range 400-800mg per day. The risk was significantly greater with 200mg twice daily (HR 1.8) than 400mg once daily (HR 1.1). Patients at greatest baseline risk were at disproportionately increased risk from celecoxib. Long-term etanercept effective in AS An open-label study suggests that etanercept (Enbrel) remains effective in the treatment of ankylosing spondylitis in the long term (Ann Rheum Dis 2008;67:346-52). Of 257 patients who completed six months' treatment with etanercept and who entered the nonblinded extension study, 126 completed a total of 168-192 weeks' treatment. The commonest adverse events were injection-site reactions (22 per cent), headache (20 per cent) and diarrhoea (17.5 per cent). The annual rate of serious infections was 0.02 per person. Response and partial remission rates after 192 weeks were similar to those reported after 96 weeks. Metformin reduces risk Metformin reduces the risk of developing diabetes in individuals at increased risk, a meta-analysis suggests (Am J Med 2008;121:149-57.e2). The study included 31 mostly small, randomised, controlled trials involving a total of 4570 participants and lasting at least eight weeks (8267 patient-years of treatment). Metformin was associated with reductions in body mass (,5.3 per cent), fasting glucose (,4.5 per cent) and insulin resistance (,22.6 per cent); lipid profiles also improved. The odds of developing diabetes were reduced by 40 per cent,an absolute risk reduction of 6 per cent over 1.8 years. MHRA clarifies cough and colds advice Press reports mistakenly suggested that the MHRA had banned some cough and cold remedies when it issued new guidance on treating young children, the MHRA says. The Agency's advice followed a review of over-thecounter cough and cold medicines for children by the Commission on Human Medicines. Children under two are at increased risk of adverse reactions and should no longer be treated with products containing antihistamine (chlorphenamine, brompheniramine, diphenhydramine), antitussives (dextromethorphan, pholcodine), expectorants (guaifenesin, ipecacuanha) and decongestants (phenylephrine, pseudoephedrine, ephedrine, oxymetazoline and xylometazoline). The MHRA said these products, which are classified as general sale medicines, should be removed from open shelves until available in new packaging that complies with the advice. They may still be supplied by a pharmacist for the treatment of older children. Coughs and colds should be treated with paracetamol or ibuprofen for fever, a simple glycerol, honey or lemon syrup for cough, and vapour rubs and inhalant decongestants for stuffy nose. Saline drops can be used to thin and clear nasal secretions in young babies. Parents are being urged not to use more than one product at a time to avoid inadvertently administering the same constituent drug twice. Perindopril brand switch Servier Laboratories is replacing its current formulations of perindopril (Coversyl, Coversyl Plus) with a new product that is not bioequivalent. The current Coversyl brand contains perindopril erbumine (also known as tert -butylamine). The new formulation contains perindopril arginine; it will be distinguished by new brand names (Coversyl Arginine, Coversyl Arginine Plus) and new packaging. Coversyl 2, 4 and 8mg tablets are equivalent to Coversyl Arginine 2.5, 5 and 10mg. Servier says the change is part of the simplification and harmonisation of global manufacturing; the arginine salt is already used in other countries and offers greater stability and a longer shelf-life. Both Coversyl and Coversyl Arginine will be in the supply chain for the next few weeks. Generic perindopril will continue to be the erbumine salt and prescriptions for generic perindopril are not affected. New from NICE Diabetes in pregnancy: management of diabetes and its complications from preconception to the postnatal period. Clinical Guidance No. 63, March 2008 This clinical guideline focuses on additional aspects of care for women with gestational diabetes (88 per cent of cases) or pre-existing diabetes (of which about 40 per cent is type 2 diabetes) and their babies. To date, insulin aspart (NovoRapid) is the only drug in the guideline specifically licensed for use in pregnancy and NICE advises obtaining informed consent to implement its recommendations for using other insulins and oral hypoglycaemic agents. As with other guidelines, NICE begins by stressing the importance of patient-centred care and involving women in decisions about their treatment. The guideline is divided into six sections, dealing with consecutive periods of pregnancy. Preconceptual planning should include empowering women to help them reduce risks, optimising glycaemic control (after retinal assessment) and increasing monitoring intensity, and providing information about the effects of pregnancy on diabetes. Metformin may be recommended as an adjunct or alternative to insulin, but other oral hypoglycaemic agents should be replaced with insulin, although glibenclamide is an option during pregnancy. Isophane insulin is the preferred long-acting insulin; lispro (Humalog) and aspart are considered safe to use. ACE inhibitors and angiotensin-II receptor blockers should be replaced with other antihypertensive agents and statins should be discontinued. Recommendations for screening and treatment of gestational diabetes build on previous guidance (CG62). Drug treatment will be needed by 10-20 per cent , this includes insulin (soluble, aspart or lispro) and/or metformin or glibenclamide, tailored to individual need. Antenatal care includes optimising glycaemic control. Insulin lispro or aspart should be considered in preference to soluble insulin. If glycaemic control cannot be achieved with insulin injections, an insulin pump may be indicated. The guideline includes a timetable for appointments and the care that should offered after each interval. Recommendations for intrapartum care, which supplement those in CG55, include frequent monitoring of blood glucose. Neonatal care includes recommendations for monitoring and screening the infant and the management of hypoglycaemia. Postnatal care (supplementing CG37) involves adjusting maternal treatment to avoid hypoglycaemia and recommendations for returning to community care. Metformin and glibenclamide are the only oral agents suitable for breastfeeding women. Women with gestational diabetes need advice about glycaemic control and planning for future pregnancies. Lifestyle advice and measurement of annual fasting plasma glucose should be offered. Inhaled corticosteroids for the treatment of chronic asthma in adults and in children aged 12 years and over. Technology Appraisal No. 138, March 2008 The latest technology appraisal of asthma treatments covers inhaled steroids for adults and children over 12 with chronic asthma. It makes only two recommendations. First, the cheapest appropriate option is recommended. Second, when a steroid and a long-acting beta2-agonist are indicated, the decision to prescribe a combined inhaler or separate devices should take into account therapeutic need and likely adherence. Combined inhalers are currently less expensive than separate devices, though they may not remain so. When a combined inhaler is chosen it should be the cheapest. NICE concludes that, at equivalent doses, there is little difference in the effectiveness or adverse event profile of the available steroids or the fixed-dose combinations. According to specialist advice, choosing the best device for an individual remains the overriding concern. Continuous positive airway pressure for the treatment of obstructive sleep apnoea/hypopnoea syndrome. Technology Appraisal No. 139, March 2008 NICE recommends continuous positive airway pressure (CPAP) for adults with moderate or severe obstructive sleep apnoea, and for those with a milder disorder if quality of life and functioning are impaired and alternative strategies such as lifestyle change have failed. Diagnosis and treatment is the responsibility of a specialist team. A CPAP device costs £250-£550 and lasts for seven years. Copyright © 2008 Wiley Interface Ltd [source]

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PRESCRIBER, Issue 9 2007
Article first published online: 3 SEP 200
Clinical trials flatter anti-TNFs in RA The efficacy of anti-TNF agents in clinical trials is not matched by experience in daily practice in patients with rheumatoid arthritis, say Dutch investigators (Ann Rheum Dis online: 10 April 2007; doi:10.1136/ard.2007.072447). They compared outcomes from a systematic review of trials of etanercept (Enbrel), infliximab (Remicade) and adalimumab (Humira) and a national postmarketing surveillance scheme (DREAM). In 5 of 11 comparisons, the response rate in DREAM was significantly lower than that in RCTs. Responses among DREAM patients who met the inclusion criteria for clinical trials were significantly greater than among noneligible patients and comparable with those of patients participating in the trials. The authors conclude that patients in trials have more severe disease and therefore a response to treatment that is not matched in daily practice. Methadone prescriptions double in 10 years Methadone treatment for opiate addicts has more than doubled in the past 10 years, according to an audit of opiate substitution in England by the National Treatment Agency for Substance Misuse (www.nta.nhs.uk). The total number of methadone prescriptions increased from 970 900 in 1995 to over 1.8 million in 2004. The introduction of buprenorphine (Subutex) has not reduced methadone prescribing , 96 per cent of responding centres prescribed methadone and 88 per cent prescribed buprenorphine. Seventy-two per cent of centres prescribe benzodiazepines to opiate addicts, causing the NTA some concern. GPs were involved in prescribing management in about 60 per cent of centres. Next NICE guidelines The Department of Health has referred eight topics to NICE for the development of clinical guidelines: preventing venous thromboembolism, acute coronary syndromes, chest pain, social complications during pregnancy (eg drug misuse), benign prostatic hyperplasia, constipation in children, neonatal jaundice and metastatic disease of unknown primary origin. Errors with children , Every step of drug treatment for children, from prescribing to writing notes, is associated with a substantial level of error, say US investigators (Quality and Safety in Health Care 2007;16:116-26). Their systematic review of 31 studies reporting medication errors in paediatrics found that 3-37 per cent were associated with prescribing errors, 5-58 per cent with dispensing errors, 72-75 per cent with errors of administration, and 17-21 per cent with documentation errors. Suggestions for remedial strategies were not evidence based, the authors found. , and transplant patients Errors in medication are common among outpatients who have received liver, kidney or pancreas transplants, a second US study has found (Arch Surg 2007;142:278-83). Twelve months' follow-up of 93 patients revealed a total of 149 errors of drug treatment, with a frequency of 15 in 219 visits over a four-week period. One-third of errors were associated with adverse events including hospital admission and graft rejection. Patients were taking an average of 11 medicines; analysis showed that over half of errors originated with the patients and 13 per cent were associated with prescribing. Paracetamol pack benefit challenged A new study has challenged accepted wisdom that reducing the OTC pack size of paracetamol cut the suicide rate (PLoS Medicine 2007;4:e105). In 1998, pack sizes of paracetamol were limited to 16 in general sale outlets and 32 in pharmacies. Suicide rates subsequently decreased but, though widely assumed, a causal link has not been established. Researchers from London and the Office of National Statistics have now examined mortality trends from suicide associated with antidepressants, aspirin, compound paracetamol preparations and nondrug poisoning. They found that all fatal suicides declined at similar rates after the pack size reductions. While not excluding the possibility that restricting easy access to paracetamol may have helped, these data suggest that other factors were also important. CV risk with ibuprofen among aspirin users Ibuprofen, but not naproxen, is associated with a higher risk of cardiovascular events and heart failure than lumiracoxib (Prexige) in high-risk patients, according to a new analysis of the TARGET trial (Ann Rheum Dis online: 5 April 2007; doi:10.1136/ard.2006.066001). TARGET comprised two studies comparing naproxen or ibuprofen with lumiracoxib in a total of 18 325 patients with OA. This post-hoc analysis stratified patients by their cardiovascular risk; the primary end-point was a composite of cardiovascular mortality, nonfatal myocardial infarction and stroke at one year. Among those at high risk who were taking aspirin, ibuprofen was associated with an increased risk of the composite end-point compared with lumiracoxib (2.14 vs 0.25 per cent). The risk was similar for naproxen and lumiracoxib (1.58 vs 1.48 per cent). In high-risk patients not taking aspirin, the risk was similar for ibuprofen and lumiracoxib, but lower for naproxen than lumiracoxib. Congestive heart failure was more common in patients taking ibuprofen than lumiracoxib (1.28 vs 0.14 per cent); the risk was similar with naproxen and lumiracoxib. The authors emphasise that their findings should be considered hypothesis-generating. CVD guidelines criticised The second edition of the guidelines of the Joint British Societies on preventing cardiovascular disease have been harshly criticised for failing to meet international quality standards (Int J Clin Pract online doi: 10.1111/j.1742-1241.2007.01310.x). Kent GP Dr Rubin Minhas evaluated the guidelines against the criteria of the Appraisal of Guidelines and Research (AGREE) Collaboration. He identified areas of weakness including stakeholder involvement, rigour of development, applicability (by not considering cost) and editorial independence from the pharmaceutical industry. The guidelines should not be recommended for clinical practice, he concludes. OTC naproxen? The MHRA is consulting on switching naproxen 250mg to pharmacy-only status for the treatment of period pain in women aged 15-50. The change would offer an alternative to ibuprofen, currently the only other OTC medicine with this indication. Responses should be submitted by 23 May. The Agency is currently considering responses to its consultation on switching tranexamic acid to OTC status for heavy menstrual bleeding. Diabetes costs The total cost of prescribing for diabetes in England has doubled in only five years, official statistics show. The NHS Information Centre (www.ic.nhs.uk) report shows that spending in primary and secondary care in 2006 was £561 million, up 14 per cent on 2005. Growth was due to increased prescribing of oral hypoglycaemic agents (notably the glitazones , up by one-third over 2005) and the higher costs of insulins. Pharmacists may give flu jabs PCTs may consider using pharmacists to administer flu vaccines to some at-risk groups in the 2007/08 season, according to Department of Health plans. Flu vaccination payment for patients with diabetes, coronary heart disease, and stroke and TIA is provided under the Quality Outcomes Framework. The Department suggests that PCTs consider contracting a local enhanced service from pharmacists to reach other patients at increased risk, such as those with chronic liver disease, multiple sclerosis and related conditions, hereditary and degenerative disease of the CNS and carers. Copyright © 2007 Wiley Interface Ltd [source]

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PRESCRIBER, Issue 4 2007
Article first published online: 3 APR 200
Low-dose aspirin may reduce asthma risk Low-dose aspirin may reduce the risk of new-onset asthma, according to a US analysis (Am J Respir Crit Care Med 2007;175:120-5). Prompted by speculation of such a link, the authors conducted a post-hoc analysis of the Physicians' Health Study, a placebo-controlled study of aspirin 325mg on alternate days involving 22 071 men aged 40-84. The risk of developing a new diagnosis of asthma during the five-year study was reduced by 22 per cent (p=0.045) among those taking aspirin. However, the number of cases was low: 113 among aspirin recipients and 145 with placebo. The clinical importance of this finding is therefore uncertain, though it received wide coverage in the lay media. Lifestyle changevsdrugs in type 2 diabetes Modifying lifestyle is at least as effective as drugs in delaying the onset of type 2 diabetes in people with impaired glucose tolerance, according to a study from Leicester (BMJ online. doi: 10.1136/bmj.39063.689375.55). The meta-analysis of 17 trials involving 8084 participants found that lifestyle change or orlistat approximately halved the risk of progressing to diabetes, whereas oral hypoglycaemic agents reduced the risk by 30 per cent. A Chinese herb, jiang tang bushen, reduced the risk by two-thirds. The analysis was conducted before the findings of major trials of rosiglitazone (Avandia) , DREAM and ADOPT , were published. Optician prescribing The diagnosis and treatment of disorders such as conjunctivitis by opticians is to be an enhanced service that PCTs can commission according to local need, a Department of Health review has concluded. The General Ophthalmic Services Review considered new arrangements to support PCTs provide ophthalmic services. Professional representatives proposed that the diagnosis and treatment of some eye conditions should be classed as ,additional services' that PCTs should be obliged to commission. While the Department agreed that opticians can play an important role, it found a lack of evidence of benefits and concluded that PCTs should be able to determine their level of services. A commissioning toolkit has been produced to help implement the review's findings. Warfarin stroke risk A four-fold increase in warfarin use has been linked with an increased incidence of intracerebral haemorrhage in a US study (Neurology 2007;68:116-21). Reviewing all first admissions for haemorrhagic stroke in the Cincinnati area, the study found that the proportion of cases associated with warfarin or heparin increased from 5 per cent in 1988 to 9 per cent in 1993/94 and 17 per cent in 1999. The annual incidence among patients aged 80 or older increased from 2.5 to 46 per 100 000 from 1988 to 1999. During the same period, warfarin distribution increased four-fold and there was no change in the incidence of thromboembolic strokes. Co-proxamol will go, MHRA reaffirms The MHRA has confirmed that it still intends to withdraw co-proxamol from the market despite protestations from MPs. The issue was raised by two MPs , one a member of the Health Select Committee , in a House of Commons debate. Both called for the withdrawal process to be abandoned, arguing that GPs should have the right to prescribe a drug for which there may be no alternative. The MHRA has restated its view that the risk from overdose with co-proxamol outweighs its benefits, adding: ,The avoidable death toll from co-proxamol overdose cannot be ignored. Sometimes regulation has to balance the needs of the individual against the benefits at a population level. In this case the removal of marketing authorisations with continued use possible in exceptional circumstances is the best balance that could be achieved. The public health gain is already becoming apparent.' Co-proxamol may still be prescribed as an unlicensed drug after its product licence is withdrawn at the end of this year. Guide to pharmacy services A guide to community pharmacy services has been published for patients, carers and members of patient organisations. Developed by the South East Local Pharmaceutical Committee Forum, Understanding and Making the Best Use of Community Pharmacy explains what pharmacies offer and the services available under the 2005 pharmacy contract. Copies can be downloaded from www.psnc.org.uk/resources. Little benefit from opioids for back pain There is little evidence that opioids relieve chronic back pain but the risk of abuse is high, according to a US analysis (Ann Intern Med 2007;146:116-27). The systematic review of trials of oral, topical and transdermal opioids in the treatment of chronic back pain found no trials lasting more than 16 weeks. There was no significant reduction in pain in placebo-controlled trials and limited, nonsignificant pain reductions in comparative trials. By contrast, estimates of prevalence of current substance misuse were as high as 43 per cent and that of ,aberrant medication-taking behaviours' ranged from 5 to 24 per cent. Dual antiplatelet therapy with drug-eluting stents Patients with drug-eluting stents should not stop dual antiplatelet therapy prematurely (Circulation 2007; published online 15 January; DOI: 10.1161/CIRCUL ATIONAHA.106.180944). Although 12 months' treatment with low-dose aspirin plus a thienopyri- dine, eg clopidogrel (Plavix) and ticlopidine, has been shown to reduce cardiac events after implanting a drug-eluting stent, it is not uncommon for the thienopyridine to be discontinued. Health professionals must do more to educate patients about their treatment and the risks associated with stopping. Scottish approval The SMC (www.scottishmedicines.org.uk) has approved varenicline (Champix) for use within NHS Scotland as part of a smoking cessation programme; it notes that the benefits of extending a course of treatment beyond the initial 12 weeks are modest. Controversially, the SMC has not approved omalizumab (Xolair) as add-on therapy for severe persistent allergic asthma on the grounds that an economic case had not been made. Asthma UK criticised the decision as unjust and inhumane. NICE is due to publish an appraisal of omalizumab later this year. No decline with anti- psychotics Treatment with anti- psychotics does not hasten cognitive decline in patients with Alzheimer's disease, say investigators from London (J Neurol Neurosurg Psychiatry 2007;78:25-9). Their prospective study of 224 patients found no difference in the rate of cognitive decline in those treated with antipsychotics (atypical or otherwise) for at least six months. Label translation online Health IT consultancy Rxinfo has developed a website offering translations of the most common types of labelling. The site (www.translabel.co.uk) offers translations into 13 Asian and European languages for 15 standard labelling phrases covering oral medicines and ENT formulations. A free application can be downloaded to allow direct-to-printer printing. Copyright © 2007 Wiley Interface Ltd [source]