Effects of vildagliptin relative to sulfonylureas in Muslim patients with type 2 diabetes fasting during Ramadan: influence of age and treatment with/without metformin in the VIRTUE study.

BACKGROUND: VIRTUE was a prospective, observational study assessing the effectiveness and safety of vildagliptin vs sulfonylureas (SUs) (both as monotherapy and in combination with metformin) in patients with type 2 diabetes mellitus who fasted during Ramadan. A post hoc analysis was carried out to assess the effect of treatment with/without metformin and age (<65 years or ≥65 years). PATIENTS AND METHODS: Patients were recruited from the Middle East and Asia. The primary end point was proportion of patients with one or more hypoglycemic event (HE) during Ramadan. Secondary end points included change from baseline in glycated hemoglobin (HbA1c), body weight, and safety. RESULTS: Overall, 684 patients received vildagliptin and 631 received SUs. Most patients received dual therapy with metformin (n=1,148) and were aged <65 years (n=1,189). A few patients experienced one or more HE with vildagliptin vs SU monotherapy (6.5% vs 14.5%) and with vildagliptin + metformin vs SUs + metformin (5.3% vs 20.6%); the latter achieved statistical significance (P<0.001) in both age subgroups (<65 years: 5.5% vs 18.4%, P<0.001; ≥65 years: 2.8% vs 30.9%, P<0.001). Vildagliptin was associated with numerically greater HbA1c and body weight reductions vs SUs, regardless of the therapy type or age. A higher proportion of SU- vs vildagliptin-treated patients experienced adverse events across all subgroups. CONCLUSION: A few patients experienced HEs with vildagliptin vs SUs regardless of age, and in patients on dual therapy. Vildagliptin ± metformin was also associated with good glycemic and weight control and was well tolerated. Vildagliptin might be a useful treatment option for patients with type 2 diabetes mellitus, particularly high-risk populations such as the elderly fasting during Ramadan.

Diabetes mellitus: Exploring the challenges in the drug development process.

Diabetes mellitus has reached epidemic proportions and continues to be a major burden on society globally. The International Diabetes Federation (IDF) estimated the global burden of diabetes to be 366 million in 2011 and predicted that by 2030 this will have risen to 552 million. In spite of newer and effective treatment options, newer delivery and diagnostic devices, stricter glycaemic targets, better treatment guidelines and increased awareness of the disease, baseline glycosylated hemoglobin remains relatively high in subjects diagnosed and treated with type 2 diabetes. The search continues for an ideal anti diabetic drug that will not only normalize blood glucose but also provide beta cell rest and possibly restoration of beta cell function. The development of anti diabetic drugs is riddled with fundamental challenges. The concept of beta cell rest and restoration is yet to be completely understood and proven on a long term. The ideal therapeutic approach to treating type 2 diabetes is not yet determined. Our understanding of drug safety in early clinical development is primarily limited to "Type A" reactions. Until marketing authorization most drugs are approved based on the principle of confirming non-inferiority with an existing gold standard or determining superiority to a placebo. The need to obtain robust pharmaco-economic data prior to marketing authorization in order to determine appropriate pricing of a new drug remains a major challenge. The present review outlines some of the challenges in drug development of anti-diabetic drugs citing examples of pulmonary insulin, insulin analogues, thiazolidinediones and the GLP1 analogues.

Intensification lessons with modern premixes: from clinical trial to clinical practice.

This paper aims to underscore the importance of insulin intensification, while highlighting the clinical utility of modern premixes through intensification lessons, by utilising data from key clinical trials, and from the recently published large observational PRESENT Study. Insulin intensification is any change made to an initial insulin regimen to improve glycaemic control. Yet, despite established glycaemic targets, current HbA1c levels in insulin-treated patients suggest that 'real-world' insulin regimens are not optimally intensified. When treatment is intensified as needed, patients are more likely to achieve and maintain glycaemic targets, as evidenced by treat-to-target trials utilising forced titration algorithms. Both clinical and observational studies suggest that modern premixes, such as biphasic insulin aspart 30, represent an effective and well-tolerated option when intensifying a number of existing insulin regimens that no longer maintain optimal glycaemic control. However, physician and patient concerns regarding initiation and intensification of insulin therapy can create barriers to effective patient care, and it is essential that such barriers be resolved. Although it is important to encourage patients to initiate insulin therapy when needed, it is equally important that insulin regimens benefit from ongoing intensification in order to maintain glycaemic control as type 2 diabetes follows its typically progressive course.

Long-term efficacy and safety of biphasic insulin aspart in patients with type 2 diabetes.

BACKGROUND: In this study, we sought to compare the long-term safety and efficacy of biphasic insulin aspart 30 (BIAsp30) with that of biphasic human insulin 30 (BHI30) over a period of 24 months in patients with type 2 diabetes. METHODS: Patients with type 2 diabetes (n=125) were assigned to twice-daily BIAsp30 or BHI30 and participated in both a 3-month initial period and a 21-month extension of a randomized, controlled, multinational trial. RESULTS: No significant difference was found in mean HbA(1c) after 24 months [BIAsp30, 8.35+/-0.20%; BHI30 8.13+/-0.16%; adjusted mean difference (BIAsp30-BHI30) 0.03 (90% CI -0.29 to 0.34)%, P=0.89]. The proportion of patients experiencing major hypoglycaemia was also similar during the first year (BIAsp30, 5%; BHI30, 8%; P=0.72), but it was significantly lower with BIAsp30 than with BHI30 during the second year (BIAsp30, 0%; BHI30, 10%; P=0.04). The proportion experiencing minor hypoglycaemia was not significantly different. No significant difference was recorded in changes in nonspecific insulin antibody levels after 24 months (BIAsp30, 4.87+/-1.92%; BHI30; 1.00+/-1.66%; P=0.13). Body weight change was 0.05+/-0.81 kg in the BIAsp30 group and 2.00+/-0.69 kg in the BHI30 group (P=0.07). CONCLUSIONS: Reduced major hypoglycaemia compared with BHI30 during the second year of treatment and comparable HbA(1c) levels after 24 months appear to support the hypothesis that the improved pharmacokinetic profile of BIAsp30 may favourably affect the balance between hypoglycaemia and hyperglycaemia in insulin-treated type 2 diabetes.