Abstract Diabetes mellitus is a common metabolic disorder characterized by high blood glucose levels resulting from an insulin deficiency (type 1 diabetes mellitus) or a combination of insulin deficiency and insulin resistance (type 2 diabetes mellitus). The chronic hyperglycemia associated with diabetes mellitus can cause damage to the eyes, kidneys, heart and peripheral circulation, resulting in substantial morbidity, premature mortality and considerable healthcare costs. In both type 1 and type 2 diabetes mellitus, quality of glycemic control has been shown to be a major factor in the prevention of microvascular complications, and tight blood glucose control is the primary goal for all patients with diabetes mellitus. In patients with type 1 diabetes mellitus, multiple daily injections of exogenous insulin and frequent monitoring of blood glucose levels are required to achieve tight glycemic control. Patients with type 2 diabetes mellitus may achieve initial glycemic control with diet and lifestyle interventions alone; however, a large percentage of patients will require pharmacological therapy, first with an oral antidiabetic agent and, ultimately, with insulin. Premixed insulin formulations, consisting of fixed ratios of short- and intermediate-acting insulins, are a convenient and effective treatment option which account for ≈40% of insulin use worldwide. Until recently, the only premixed formulations available contained varying proportions of human regular insulin and human isophane insulin suspension (NPH). However, new premixed formulations containing insulin lispro (a rapid-acting insulin analog) and insulin lispro neutral protamine suspension (NPL) [an intermediate-acting insulin analog] are now available. Insulin lispro mix75/25 (Humalog® Mix75/25™) is a premixed formulation containing 25% insulin lispro and 75% NPL which has been investigated for use in patients with type 1 and with type 2 diabetes mellitus. Administered twice daily immediately before breakfast and dinner, insulin lispro mix75/25 provides better control of postprandial blood glucose, provides similar overall glycemic control, appears to be preferred by patients and may reduce nocturnal hypoglycemia compared with a similar premixed formulation containing 30% human regular insulin and 70% NPH (human insulin 70/30; Humulin® 70/30, Novolin® 70/30). Insulin lispro mix75/25 has a rapid onset of action, allowing for administration immediately before a meal, whereas patients need to administer human insulin 70/30 30 to 60 minutes prior to meals. Insulin lispro mix75/25 also improves glycemic control in patients whose type 2 diabetes mellitus is not well controlled by oral agents. Conclusion Insulin lispro mix75/25 is suitable for patients wishing to use premixed insulin formulations and may offer several benefits over human insulin 70/30.

Latanoprost (Xalatan) is an ester analogue of prostaglandin F2alpha that reduces intraocular pressure (IOP) by increasing uveoscleral outflow. The IOP-lowering efficacy of latanoprost 0.005% lasts for up to 24 hours after a single topical dose, which allows for a once-daily dosage regimen. In patients with ocular hypertension or open-angle glaucoma, a single drop of latanoprost 0.005% solution (about 1.5 microg) administered topically once daily reduced diurnal IOP by 22 to 39% over 1 to 12 months' treatment in well-controlled trials; efficacy was maintained during treatment periods of up to 2 years. At this dosage, latanoprost was significantly more effective than timolol 0.5% twice daily in 3 of 4 large, double-blind, randomised studies, was generally as effective as bimatoprost or travoprost, and was significantly more effective than dorzolamide, brimonidine or unoprostone. Furthermore, in patients whose IOP was poorly controlled with timolol, switching to latanoprost monotherapy was at least as effective at lowering IOP as adding dorzolamide or pilocarpine to the regimen. Latanoprost has also shown significant additive effects when used in combination with one or more other glaucoma medications. The fixed combination of latanoprost plus timolol was significantly more effective than either of its individual components in two double-blind randomised studies and more effective than the fixed combination of dorzolamide and timolol in a 3-month, evaluator-masked study. Data in patients with angle-closure glaucoma are limited, but in patients with elevated IOP after undergoing iridotomy, latanoprost 0.005% once daily was significantly more effective than timolol 0.5% twice daily at reducing IOP over 12 weeks of treatment in a large double-blind, randomised study. Latanoprost is generally well tolerated and, unlike timolol, induces minimal systemic adverse events. In well-controlled, 6-month trials, the most commonly occurring drug-related ocular events in latanoprost recipients were mild to moderate conjunctival hyperaemia (3 to 15%) and iris colour change (2 to 9%); these seldom required patient withdrawal although the latter may be permanent. Latanoprost 0.005% as a single daily drop has shown good IOP-lowering efficacy in patients with open-angle glaucoma or ocular hypertension and does not produce the cardiopulmonary adverse effects associated with beta-blockers. Thus, latanoprost is a valuable addition to the first-line treatment options for patients with open-angle glaucoma or ocular hypertension. In addition, adjunctive treatment with latanoprost in patients who are refractory to beta-blocker therapy is a viable, second-line treatment option. Although preliminary findings are promising, wider clinical experience is required to define the place of latanoprost in the treatment of angle-closure glaucoma.

Etanercept (Enbrel®2) is a subcutaneously administered biological response modifier that binds and inactivates tumour necrosis factor-α, a proinflammatory cytokine.

▴ Gefitinib (ZD1839) is an orally active selective inhibitor of epidermal growth factor receptor tyrosine kinase, an enzyme that regulates intracellular signalling pathways implicated in the proliferation and survival of cancer cells.

Type 2 diabetes mellitus is a progressive disease with an insidious onset. It is thought to affect up to 10% of European and North American populations with a significantly higher incidence in non-White than in White populations. Complications of the disease are associated with considerable morbidity and mortality and their management consumes significant healthcare resources.Data from the United Kingdom Prospective Diabetes Study have shown that intensive glycemic control reduces the microvascular complications of type 2 disease and that intensive management of fasting plasma glucose (FPG) levels is insufficient over time to provide such control. Recent studies have demonstrated that lowering postprandial plasma (PPG) glucose levels provides some additional glycemic control and recent epidemiologic data suggest reducing PPG levels may be associated with a reduction in mortality.In patients with type 2 diabetes mellitus inadequately controlled by diet and exercise, nateglinide significantly improved glycemic control compared with placebo; a beneficial effect on both FPG and PPG levels was observed. In active comparator studies, nateglinide has been shown to be as effective as metformin (in pharmacotherapy-nave patients), acarbose and troglitazone in reducing glycosylated hemoglobin (HbA(1c)) levels.When used in combination with metformin (in patients inadequately controlled on maximum dosages of metformin monotherapy) nateglinide significantly improves glycemic control compared with placebo. In addition, nateglinide has been shown to display pronounced additive effects when added to troglitazone or metformin in patients inadequately controlled by diet and exercise alone.Nateglinide was generally well tolerated in clinical trials. The most common adverse event was hypoglycemia, although the incidence was low in comparison with sulfonylureas. The incidence of hypoglycemia was increased in patients using nateglinide in combination with metformin.By controlling HbA(1c) and PPG, nateglinide has the potential to provide substantial health and quality-of-life benefits; however, long-term outcome data and validated quality-of-life assessments are lacking. In economic modelling studies, the estimated cost-effectiveness ratios observed with nateglinide were well within the range for therapies considered to be cost-effective.In conclusion, nateglinide is a useful addition to the available treatments for type 2 diabetes mellitus. It significantly improved glycemic control in pharmacotherapy-naive patients as well as in patients not adequately controlled by metformin alone; however, until long-term clinical data become available, nateglinide can only be considered as an adjunct to metformin in patients inadequately controlled on metformin alone in whom PPG levels are elevated. Nateglinide is well tolerated and has low potential to cause hypoglycemia and bodyweight gain.

Quinapril is rapidly de-esterified after absorption to quinaprilat (the active diacid metabolite), a potent angiotensin converting enzyme (ACE) inhibitor. Quinapril produces. favourable haemodynamic changes, and improves ventricular and endothelial function in patients with various cardiovascular disorders; these. effects are mediated through the binding of quinaprilat to both tissue and plasma ACE.Quinapril 10 to 40 mg/day provided effective blood pressure control in most patients with essential hypertension in clinical trials, but some patients required dosages of 80 mg/day and/or concomitant diuretic therapy. In general, quinapril provided similar blood pressure control to other standard antihypertensive therapies including other ACE inhibitors, calcium antagonists and beta-adrenoceptor antagonists in comparative clinical trials. Combined therapy with quinapril and hydrochlorothiazide. had a significantly greater antihypertensive effect than either drug as monotherapy in two well designed studies. Quinapril has also been shown to reduce microalbuminuria in patients with hypertension and/or diabetes mellitus.In patients with congestive heart failure, quinapril less than or equal to40 mg/day produced beneficial haemodynamic and echocardiographic changes and improved exercise tolerance, symptoms and functional class. Effects of quinapril on survival have not been investigated, but quinapril 10 to 20 mg/day showed comparable efficacy to captopril 25 to 50mg twice daily in two well designed trials.In patients with coronary artery disease, quinapril 40 mg/day significantly reduced the incidence of ischaemic events after coronary artery bypass grafting (CABG) in a well controlled study (n = 148). However, a lower dosage of quinapril (20 mg/day) showed no effect on ischaemic events or atherosclerotic progression with 3 years of treatment in a similarly designed study involving 1750 patients undergoing coronary angioplasty.The tolerability of quinapril is similar to that of other ACE inhibitors. In placebo-controlled trials, cough occurred in 2 and 4.3% and hypotension occurred in <1 and 2.9% of quinapril recipients with hypertension or congestive heart failure, respectively. No increase in adverse events was observed when the dosage was increased from 10 to 40 mg/day.Conclusion: Quinapril is now firmly established as an effective and well tolerated ACE inhibitor for the treatment of patients with hypertension and congestive heart failure. Quinapril 40 mg/day also significantly reduced the incidence of ischaemic events in patients undergoing CABG in one study; however, a lower dosage of quinapril (20 mg/day) had no effect on ischaemic events in patients undergoing coronary angioplasty in another trial. Additional trials in patients with coronary artery disease receiving optimal dosages of quinapril (40 mg/day) would be useful.

Repaglinide, a carbamoylmethyl benzoic acid derivative, is the first of a new class of oral antidiabetic agents designed to normalise postprandial glucose excursions in patients with type 2 diabetes mellitus. Like the sulphonylureas, repaglinide reduces blood glucose by stimulating insulin release from pancreatic beta-cells, but differs from these and other antidiabetic agents in its structure, binding profile, duration of action and mode of excretion. In clinical trials of up to 1-year's duration, repaglinide maintained or improved glycaemic control in patients with type 2 diabetes mellitus. In comparative, 1-year, double-blind, randomised trials (n = 256 to 544), patients receiving repaglinide (0.5 to 4mg before 3 daily meals) achieved similar glycaemic control to that in patients receiving glibenclamide (glyburide) < or = 15 mg/day and greater control than patients receiving glipizide < or = 15 mg/day. Changes from baseline in glycosylated haemoglobin and fasting blood glucose levels were similar between patients receiving repaglinide and glibenclamide in all studies; however, repaglinide was slightly better than glibenclamide in reducing postprandial blood glucose in I short term study (n = 192). Patients can vary their meal timetable with repaglinide: the glucose-lowering efficacy of repaglinide was similar for patients consuming 2, 3 or 4 meals a day. Repaglinide showed additive effects when used in combination with other oral antidiabetic agents including metformin, troglitazone, rosiglitazone and pioglitazone, and intermediate-acting insulin (NPH) given at bedtime. In 1-year trials, the most common adverse events reported in repaglinide recipients (n = 1,228) were hypoglycaemia (16%), upper respiratory tract infection (10%), rhinitis (7%), bronchitis (6%) and headache (9%). The overall incidence of hypoglycaemia was similar to that recorded in patients receiving glibenclamide, glipizide or gliclazide (n = 597) [18%]; however, the incidence of serious hypoglycaemia appears to be slightly higher in sulphonylurea recipients. Unlike glibenclamide, the risk of hypoglycaemia in patients receiving repaglinide was not increased when a meal was missed in 1 trial. In conclusion, repaglinide is a useful addition to the other currently available treatments for type 2 diabetes mellitus. Preprandial repaglinide has displayed antihyperglycaemic efficacy at least equal to that of various sulphonylureas and is associated with a reduced risk of serious hypoglycaemia. It is well tolerated in a wide range of patients, including the elderly, even if a meal is missed. Furthermore, glycaemic control is improved when repaglinide is used in combination with metformin. Thus, repaglinide should be considered for use in any patient with type 2 diabetes mellitus whose blood glucose cannot be controlled by diet or exercise alone, or as an adjunct in patients whose glucose levels are inadequately controlled on metformin alone.

Diabetes mellitus is a common metabolic disorder characterized by high blood glucose levels resulting from an insulin deficiency (type 1 diabetes mellitus) or a combination of insulin deficiency and insulin resistance (type 2 diabetes mellitus). The chronic hyperglycemia associated with diabetes mellitus can cause damage to the eyes, kidneys, heart and peripheral circulation. resulting in substantial morbidity, premature mortality and considerable healthcare costs.In both type 1 and type 2 diabetes mellitus, quality of glycemic control has been shown to be a major factor in the prevention of microvascular complications, and tight blood glucose control is the primary goal for all patients with diabetes mellitus. In patients with type 1 diabetes mellitus, multiple daily injections of exogenous insulin and frequent Monitoring of blood glucose levels axe required to achieve tight glycemic control. Patients with type 2 diabetes mellitus may achieve initial glycemic control with diet and lifestyle interventions alone; however. a large percentage of patients will require pharmacological therapy, first with an oral antidiabetic agent and, ultimately, with insulin.Premixed insulin formulations, consisting of fixed ratios of short- and intermediate-acting insulins, are a convenient and effective treatment option which account for approximate to40% of insulin use worldwide. Until recently, the only premixed formulations available contained varying proportions of human regular insulin and human isophane insulin suspension (NPH). However, new premixed formulations containing insulin lispro (a rapid-acting insulin analog) and insulin lispro neutral protamine suspension (NPL) [an intermediate-acting insulin analog] are now available.Insulin lispro mix75/25 (Humalog(R) Mix75/25(TM)) is a premixed formulation containing 25% insulin lispro and 75% NPL which has been investigated for use in patients with type I and with type 2 diabetes mellitus, Administered twice daily immediately before breakfast and dinner, insulin lispro mix75/25 provides better control of postprandial blood glucose, provides similar overall glycemic control, appears to be preferred by patients and may reduce nocturnal hypoglycemia compared with a similar premixed formulation containing 30% human regular insulin and 70% NPH (human insulin 70/30; Humulin(R) 70/30, Novolin(R) 70/30). Insulin lispro mix75/25 has a rapid onset of action, allowing for administration immediately before a meal, whereas patients need to administer human insulin 70/30 30 to 60 minutes prior to meals, Insulin lispro mix75/25 also improves glycemic control in patients whose type 2 diabetes mellitus is not well controlled by oral agents.Conclusion: Insulin lispro mix75/25 is suitable fur patients wishing to use premixed insulin formulations and may offer several benefits over human insulin 70/30.

Diabetes mellitus is a common metabolic disorder characterized by high blood glucose levels resulting from an insulin deficiency (type 1 diabetes mellitus) or a combination of insulin deficiency and insulin resistance (type 2 diabetes mellitus). The chronic hyperglycemia associated with diabetes mellitus can cause damage to the eyes, kidneys, heart and peripheral circulation, resulting in substantial morbidity, premature mortality and considerable healthcare costs.

▴ 131I tositumomab is a radiolabelled murine anti-CD20 monoclonal antibody that binds specifically to the CD20 antigen on normal and malignant B lymphocytes. It has antitumour activity as a result of emission of beta particles, and activation of antibody-dependent cellular and complement-mediated cytotoxicity.

Contemporary asthma management guidelines list inhaled corticosteroids as the preferred controller medication for patients with persistent asthma. Despite the availability of explicit guidelines, there is evidence that these agents are underused and that guidelines are not always adhered to.