Search

The efficacy of monotherapy to reduce pain from diabetic peripheral neuropathy (DPN) is frequently not satisfactory and guidelines do not provide unanimous treatment options. In this context, multiple drug pharmacotherapy may provide benefit.The aim of the present review is to describe the clinical trials addressing the pharmacotherapy of painful DPN. Studies discussing efficacy and tolerability of pharmacological agents that were assessed in monotherapy and in combination treatment are reported and discussed.Several clinical trials have reported benefit of multiple-drug pharmacotherapy. Nevertheless, untoward effects of combination treatment are of concern. Importantly, some trials were restricted to comparison with placebo and other compared only with active comparator(s). Only limited clinical trials assessed selected cohorts of individuals experiencing different stages of painful DPN. Despite current limitations, some evidence of studies implicating a comparison to all active comparators points to safety and effectiveness of the combination of oxycodone with pregabalin and that of pregabalin with the 5% lidocaine plaster but future, clear-cut studies are required to drive evidence-based decisions in the clinical setting.

Standard treatment for diabetic foot ulcers (DFUs) includes off-loading, debridement, moisture balance, management of infection and peripheral arterial disease (PAD) as well as adequate glycemic control. The outcomes so far are unsatisfactory.Herein, the authors provide an outline of newer pharmacological agents for the management of DFUs and give their expert perspectives on future treatment strategies.Evidence-based healthcare calls for high quality evidence from large RCTs before the implementation of new guidelines for the management of DFUs. Empagliflozin and liraglutide can be recommended for glucose control in patients with DFUs and PAD, while intensive lipid lowering therapy with evolocumab when primary cholesterol goals are not met could be offered to patients with DFUs. Further clinical studies are warranted to develop a structured algorithm for the treatment of DFUs that fail to heal after four weeks of current standard of care. Sucrose octasulfate dressings, becaplermin gel, and platelet-rich plasma (PRP) could also be considered as advanced treatment options for the management of hard to heal DFUs.

Introduction: In women with type 1 diabetes mellitus (T1DM), pregnancy is associated with a potential risk of maternal, foetal and neonatal outcomes. Stringent metabolic control is required to improve these outcomes. Areas covered: In this review, the authors summarise the current evidence from studies on the pharmacological therapy and on monitoring of T1DM during pregnancy. The authors also discuss the use of new technologies to improve therapeutic management and patient compliance. Expert opinion: Pre-conception counselling is essential in T1DM to minimise pregnancy risks. Pregnancy in T1DM is always considered a high-risk pregnancy. During pregnancy, the target haemoglobin A1C (HbA1c) is near-normal at

It is known that diabetes is associated with the development of premature atherosclerosis and microvascular complications and consequently increased cardiovascular (CV) morbidity and mortality. In ...

Neuropathy is a serious complication of diabetes. Its management focuses on glycaemic control, multifactorial cardiovascular risk intervention, pathogenesis-oriented therapy, and analgesics where needed.The objective of this review is assessment of efficacy and safety of α lipoic acid (ALA, also thioctic acid) in pathogenesis-oriented treatment of diabetic neuropathy. The mechanisms of action of ALA in experimental diabetic neuropathy include reduction of oxidative stress along with improvement in nerve blood flow, nerve conduction velocity, and several other measures of nerve function. There is ample evidence from randomised, double-blind, placebo-controlled clinical trials and meta-analyses, suggesting that ALA is efficacious and safe for the diabetic neuropathy, accomplishing clinically meaningful improvements.ALA is a valuable therapeutic option for diabetic neuropathy. When compared with currently licensed analgesic drugs, it is better tolerated, has a more rapid onset of action, and improves paraesthesiae, numbness, sensory deficits, and muscle strength in addition to neuropathic pain. In clinical practice, ALA may be chosen in patients with early neuropathic deficits and symptoms, in whom clinical improvement is more likely. ALA should also be considered when comorbidities render other analgesics less appropriate or in the presence of cardiovascular autonomic neuropathy.

Several drugs are available for the treatment of type 2 diabetes mellitus (T2DM), but few patients achieve and maintain glycaemic control without weight gain and hypoglycaemias. Sodium glucose co-transporter 2 (SGLT-2) inhibitors are an emerging class of drugs with an original mechanism of action involving inhibition of renal glucose reabsorption. Two agents of this class, dapagliflozin and canagliflozin, have already been approved, although we need more data on cardiovascular outcomes along with bladder and breast cancer. Tofogliflozin is a further SGLT-2 inhibitor, which exhibits the highest selectivity for SGLT-2, the most potent antidiabetic action and a reduced risk of hypoglycaemia. Recently, a 52-week, multicentre, open-label, randomised controlled trial in Japanese T2DM patients has shown that tofogliflozin exhibits adequate safety and efficacy as monotherapy or as add-on treatment in patients suboptimally controlled with oral agents. Despite the very promising characteristics of this new drug, important questions remain to be answered, mainly additional data on safety outcomes and potential beneficial effects of tofogliflozin, for instance in prediabetes and diabetic nephropathy. Moreover, it would be welcome to examine the utility of its therapeutic use in combination with insulin and metformin.

Bronchodilators represent the mainstay of symptomatic treatment for chronic obstructive pulmonary disease (COPD). The principal bronchodilator agents are β(2)-agonists, anticholinergics and methylxanthines, used singly or in combination. Indacaterol is a novel long-acting β(2)-agonist for maintenance bronchodilator treatment of airflow obstruction in patients with COPD, approved in December 2009 by the European Medicines Association, and recently by the US Food and Drug Administration. It is administered once daily and is delivered by means of a single-dose dry powder inhaler (SDDPI). In Europe, the recommended dose is 150 μg and the maximum dose is 300 μg, while in the US the recommended dose is 75 μg. Indacaterol shows evidence of a rapid onset of bronchodilation, and its bronchodilatory duration is sustained.Numerous clinical studies have assessed the therapeutic effects of indacaterol in various physiologic parameters, as well as symptoms, disease progression, exacerbation rates, quality of life, safety and tolerability. This review summarises published evidence regarding the efficacy, tolerability and safety of indacaterol in regard to lung function and symptoms of COPD patients.Indacaterol, the novel once-daily β(2)-agonist, has rapid and sustained bronchodilatory effect, showing excellent efficacy, tolerability and safety, as shown by all clinical trials so far.

Metformin represents the cornerstone of treatment for type 2 diabetes mellitus. Traditionally, heart failure (HF) was considered a contraindication to its use. However, more recent evidence has shown that this should no longer be the case. Indeed, studies have demonstrated that metformin may even reduce the risk of incident HF and mortality in diabetic patients, while improving up to 2-year survival rates in those with HF. In addition, it appears to exert cardioprotective actions. Although longer follow-up data and more explicit information about the situation in patients with very advanced HF are needed, the cardiac safety of metformin has profound clinical implications and may be anticipated to further encourage its widespread use.

Several classes of drugs have been developed to treat type 2 diabetes mellitus (T2DM). Pioglitazone is now the only thiazolidinedione approved for the treatment of T2DM and can be administered in combination with metformin, sulfonylureas, exenatide, dipeptidyl peptidase 4 (DPP-4) inhibitors or insulin. It improves glycemic control with an extremely low incidence of hypoglycemia. In addition to reducing insulin resistance, it may also improve pancreatic beta-cell secretory function. Moreover, it exhibits a variety of favorable pleiotropic effects. The latter include anti-inflammatory, antioxidant, vasoprotective, antihypertensive and hypolipidemic actions. Finally, this agent has been shown to improve experimental diabetic neuropathy and alleviate neuropathic pain, as well as decreasing urinary albumin excretion in patients with diabetes. Thus, pioglitazone emerges as a valuable hypoglycemic agent for combination therapy in T2DM. Importantly, however, patients should be appropriately selected, especially to avoid those with heart failure, in order to minimize adverse events attributable to water retention.

The present study was undertaken to assess the impact of the angiotensin-converting enzyme (ACE) insertion (I)/deletion (D) polymorphisms on circulating markers of collagen type I synthesis and degradation, and also to study the effect of therapy with ACE inhibitors on these markers in hypertensive patients with atrial fibrillation (AF).ACE I/D genotypes were assessed in 158 hypertensive patients (71 +/- 9 years; 72 male) with AF and 174 patients with arterial hypertension in sinus rhythm (SR) (71 +/- 9 years; 88 male). Serum concentrations of amino-terminal propeptide of pro-collagen type I (PINP) and of carboxy-terminal telopeptide of collagen type I (CITP), indices of collagen type I synthesis and degradation, respectively, were measured.Of the 332 study participants, 74 (22.3%) were I/I, 158 (47.6%) were I/D and 100 (30.1%) were D/D carriers. Genetic variation in ACE significantly influenced serum CITP levels in AF patients (p = 0.011). CITP levels were lower in D allele carriers (DD and ID) compared with I/I carriers. There was no difference in PINP levels between the different ACE genotype groups (p = 0.302). Patients treated with ACE inhibitors had higher CITP levels compared with those not treated (p = 0.036).This study suggests that the presence of the D allele in hypertensive patients with AF is associated with attenuation of type-I collagen degradation, and that therapy with ACE inhibitors increases degradation of collagen type I. The data indicate a subgroup of patients with AF and arterial hypertension who may benefit to a greater extent from therapy with ACE inhibitors, thus, providing a basis for pharmacogenetics.

Glycosuria is being increasingly recognised as not only a symptom but also as a novel therapeutic approach in the management of type 2 diabetes mellitus (T2DM). This is accomplished through sodium glucose co-transporter 2 (SGLT2) inhibitors. Consequently, the safety and efficacy of these new agents have been thoroughly studied, both in randomised controlled trials and in systematic reviews and meta-analyses. More recently, a review on the mechanism of action, clinical efficacy and safety of luseogliflozin, a new highly selective SGLT2 inhibitor approved and launched in Japan for T2DM, has documented that this drug lowers plasma glucose concentration and body weight, and that it exhibits benefits in other metabolic parameters with a good safety profile. Despite the promising characteristics of this drug, important issues await consideration. These include the question as to when and to whom early use of SGLT2 inhibitors would be most suitable, as well as instructions on reduction of sulfonylurea dosage during add-on treatment. Further important questions are long-term safety concerns and cost-effectiveness of this new therapeutic class. Finally, we need to know more about the potential differences between the various SGLT2 inhibitors, as such differences might prove clinically useful in selection of hypoglycaemic agents.