Search

ABSTRACTIntroductionThe 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.Areas coveredThe 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.Expert opinionSeveral 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.

Background: Cardiovascular autonomic neuropathy (CAN) and distal symmetrical sensorimotor polyneuropathy (DSPN) are serious microvascular complications of diabetes mellitus (DM). Their simultaneous development remains disputable. The aim of the present study was to examine the correlation between CAN and the presence/severity of DSPN in DM. Methods: Subjects with type 1 (group A: n=51; mean age 40.4 years) and type 2 DM (group B: n=153; mean age 64.6 years) were studied. Evaluation of DSPN was based on neuropathy disability score. Assessment of CAN was based on the battery of 4 standardized cardiovascular autonomic function tests. Results: In group A, patients with moderate/severe DSPN exhibited a 12-fold higher likelihood of CAN in univariate analysis (p=0.035). However, significance was lost after adjustment for gender, age, DM duration, and haemoglobin A1c. In group A, likelihood for CAN did not correlate with the presence of mild DSPN in univariate and multivariate analysis. In group B, likelihood of CAN was similar in patients with mild and in those with moderate/severe DSPN compared with patients without DSPN in univariate and multivariate analysis. In between group comparison CAN was similarly distributed in the 2 groups (p for interaction=0.367), in patients with no, mild and moderate/severe DSPN. Conclusion: CAN does not always co-exist with degrees of DSPN, ranging from mild to moderate/ severe and is similarly distributed in T1DM and T2DM patients with mild and moderate/severe DSPN and in patients without DSPN.

ABSTRACTIntroduction: 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 <6%, without excessive hypoglycaemia. Strict control of pre- and post-prandial glucose is also required. Human soluble insulin, neutral protamine Hagedorn and the quick-acting insulin analogues aspart and lispro are widely used. Insulin is administered either as a basal-bolus regimen or by continuous subcutaneous insulin infusion. Careful and strict glucose monitoring is also needed during labour and delivery, including caesarean section. Moreover, the control of retinopathy, hypertension, nephropathy, hyper- and hypothyroidism is required. Post-partum, insulin requirements decrease, and less stringent glycaemic control is pursued, to avoid hypoglycaemias. Finally, breastfeeding is recommended and should be encouraged.

ABSTRACTIntroduction: Gestational diabetes mellitus (GDM) represents impaired carbohydrate metabolism during pregnancy and is characterized by progressive insulin resistance and compensatory hyperinsulinaemia. If inadequately treated, it may lead to fetal macrosomia and other adverse outcomes.Areas covered: In this review, the authors summarize the current evidence from studies on the use of insulin and other agents for the treatment of women with GDM.Expert opinion: Lifestyle management is of paramount importance for the treatment of GDM. In pharmacotherapy, insulin remains the long-established mainstay of treatment. NPH (Neutral Protamine Hagedorn) and soluble human insulin have long been established for use, but favorable experience has now also accumulated with the newer insulins (aspart, lispro, detemir). Alternatively, metformin and glyburide have been used in GDM, but they have never gained wide acceptance. Nutritional supplements based on micronutrients and bioactives (probiotics and myoinositol) have shown promising results as well. Further experience with incretin agents (DPP-4 inhibitors and GLP-1 receptor agonists) is awaited.

Hormonal changes during pregnancy can trigger gestational diabetes (GDM), which is constantly increasing. Its main characteristic is pronounced insulin resistance, but it appears to be a multifactorial process involving several metabolic factors; taken together, the latter leads to silent or clinically evident cardiovascular (CV) events. Insulin resistance and central adiposity are of crucial importance in the development of metabolic syndrome, and they appear to correlate with CV risk factors, including hypertension and atherogenic dyslipidaemia. Hypertensive disease of pregnancy (HDP) is more likely to be an accompanying co-morbidity in pregnancies complicated with GDM. There is still inconsistent evidence as to whether or not co-existent GDM and HDP have a synergistic effects on postpartum risk of cardiometabolic disease; however, this synergism is becoming more accepted since both these conditions may promote endothelial inflammation and early atherosclerosis. Regardless of the presence or absence of the synergism between GDM and HDP, these conditions need to be dealt early enough, in order to reduce CV morbidity and to improve health outcomes for both women and their offspring.

ABSTRACTIntroduction: In 2017, the management of type 1 diabetes mellitus (T1DM) remains intriguing for the clinician, who has to balance between adequate glycemic control and untoward events related to insulin up-titration. Thus, agents that will complement insulin actions and reduce adverse effects are highly welcome.Areas covered: In this review, the authors summarize results from studies on the sodium glucose co-transporter 2 (SGLT2) inhibitor dapagliflozin in T1DM.Expert opinion: In T1DM, dapagliflozin is associated with significant antihyperglycemic and metabolic properties, which are achieved with reduction or stabilization of insulin dose and with a very low trend for hypoglycemia. However, there is a lot to learn with respect to diabetic ketoacidosis (DKA), bone fractures and lower limb ischemia.

ABSTRACTIntroduction: Sodium-glucose co-transporter 2 (SGLT-2) inhibitors are a new class of drugs that are increasingly used for the management of type 2 diabetes mellitus (T2DM). Among these, tofogliflozin has recently received marketing approval in Japan.Areas covered: In this review, the authors summarize the pharmacokinetic and pharmacodynamic profile of tofogliflozin for the treatment of T2DM, and provide a rationale for its use in such patients.Expert opinion: Despite the very promising characteristics of tofogliflozin in improvement of glycemic and metabolic parameters, a number of issues await consideration. One important question relates to the manner in which tofogliflozin mediates metabolic changes. Additionally, safety issues, namely hypoglycemia, diabetic ketoacidosis, pollakiuria and polyuria, urinary and genital tract infections, and potential other adverse events, need to be better monitored by pharmacovigilance programs. Ultimately, although tofogliflozin seems a promising agent that physicians are likely to embrace with excitement in the T2DM therapeutic area, longer duration trials are expected to verify this speculation and to increase our experience.

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.

Introduction:Insulin is the cornerstone of type 1 diabetes mellitus (T1DM) therapy. However, it cannot achieve a delay in the onset or evolution of this condition, while cardiovascular morbidity remains an unquestionable threat.Areas covered:In this review, the authors discuss gevokizumab(XOMA 052), a recombinant monoclonal antibody that can neutralize human IL-1β by binding to it. This is relevant, because this IL has been associated with β-cell toxicity in both diabetes types. Moreover, gevokizumab presents two major advantages: it spares IL-1α and it exhibits favorable pharmacokinetic properties. Gevokizumab has already proven its safety and efficacy in improving glycemic control, β cell function and inflammation markers in clinical trials in diabetic patients.Expert opinion:Despite the very promising characteristics of gevokizumab, important questions remain to be answered. One important question is what to expect from a combination of this agent with insulin and if there is a subset of patients that might respond more favorably to treatment. We also need to know at what stage in the natural history of T1DM could gevokizumab be most efficacious, as well as its potential effects on cardiovascular outcomes.

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.

FlexTouch® (FT) is a new prefilled insulin pen with the unique characteristic of no extendable push button at any dose setting and consequently a low activation force. Its technical features along with health care professionals' and patients' preferences in comparison to other traditionally used devices for insulin delivery have already been investigated. Recently, a study of injection force and accuracy using FT in the delivery of new basal insulin has compared FT with the insulin pens KwikPen® and SoloStar® and has shown that FT exhibits preciseness in insulin delivery of all insulin formulations and a significantly lower activation force than the other two insulin injectors. Despite the very promising characteristics of this new device, important questions remain to be answered, mainly the possible promotion of treatment adherence and the notion of confidence in self-administration of insulin. Moreover, an analysis of patients' perception on injecting higher doses with FT in comparison to other insulin injectors would be useful.