DIABETES MELLITUSD iabetes mellitus (DM) is a metabolic disorder resulting from a defect in insulin secretion, insulin action or both [1][2][3][4]. Insulin defi ciency in turn leads to chronic hyperglycaemia with disturbances of carbohydrate, fat and protein metabolism [1][2][3][4]. As the disease progresses tissue or vascular damage ensues leading to severe diabetic complications such as retinopathy [5,6], neuropathy [7,8], nephropathy [9,10], Cardiovascular complications [11,12] and ulceration [13,14]. Th us diabetes covers a wide range of heterogeneous diseases. Diabetes is the most common endocrine disorder and by the year 2010, it was estimated that more than 200 million people worldwide had DM and 300 million will subsequently have the disease by 2025 [15][16][17]. Th e diagnostic criteria and the classifi cation of diabetes was fi rst put forward by the World Health Organization (WHO) in 1965[18] then by the National Diabetes Data Group (NDDG) in 1979 [19] and this was followed by simplifi ed recommendations by the WHO in 1980 [20]. Th ese WHO recommendations were modifi ed slightly in 1985 [21]. Th e latest recommendations have been published by the American Diabetes Association (ADA) in 1997 and by the WHO in 1999. Both groups agree on the recommendations and criteria [2,22].According to the ADA recommendation changes in 1997, the fasting glucose concentration should be used in routine screening for diabetes as well as epidemiological studies; the threshold for fasting glucose was changed from 7.8 mmol/L (140 mg/dl) to 7.0 mmol/L (126 mg/dl); however the 2 hrs glucose criterion remains as 11.1 mmol/L (200 mg/dL). For the diagnosis of diabetes, at least one of the below criteria must apply. Th e WHO diagnosis and classifi cation of diabetes mellitus (1999) are identical to those of ADA, a fasting glucose = 7.0 mmol/L (126 mg/dl) and /or a 2 hrs glucose = 11.1 mmol/L (200 mg/dL). Th e report states that diagnosis should not be based on a single glucose determination but requires confi rmatory symptoms or blood/plasma determination. Ideally therefore, both the 2 hrs and fasting value should be used. Th ese recommendations contrast with those of ADA Expert Committee which gives primacy to the fasting plasma glucose. Th e WHO classifi cation includes both clinical stages (normoglycaemia, impaired glucose tolerance/impaired fasting glucose (IGT/IFG), diabetes and aetiological types of diabetes mellitus, identical to the ADA except that WHO group includes classifi cation formerly known as gestational impaired glucose tolerance (GIGT) and GDM: fasting glucose = 7.0 mmol/L (126 mg/dL) and/or 2 hrs glucose = 7.8 mmol/ L (140 mg/dL) after a 75-g OGTT.Diabetes mellitus may be categorized into several types but the two major types are type I and type II [21,23]. On the basis of aetiology, the term type I and type II were widely used to describe IDDM and NID-DM, respectively. Th e term juvenile -onset diabetes has sometimes been used for IDDM and maturity-onset for NIDDM.Type I (Ia, Ib) ß-cell destruction with litt...

Insulin glargine is a long-acting analogue of human insulin that has been used to manage hyperglycemia in patients with diabetes mellitus (DM) for nearly 20 years. Insulin glargine has a relatively constant concentration-time profile that mimics basal levels of insulin and allows for once-daily administration. MYL-1501D is a biosimilar insulin glargine designed to offer greater access of insulin glargine to patients, with comparable efficacy and safety to the marketed reference product. We conducted a comprehensive panel of studies based on a formal analysis of critical quality attributes to characterize the structural and functional properties of MYL-1501D and reference insulin glargine products available in the United States and European Union. MYL-1501D was comprehensively shown to have high similarity to the reference products in terms of protein structure, metabolic activity (both in vitro cell-based assays and in vivo rabbit bioassays), and in vitro cell-based assays for mitogenic activity. The structural analyses demonstrated that the primary protein sequence was identical, and secondary and tertiary structures are similar between the proposed biosimilar and the reference products. Insulin receptor binding affinity and phosphorylation studies also established analytical similarity. MYL-1501D demonstrated high similarity in different metabolic assays of glucose uptake, adipogenesis activity, and inhibition of stimulated lipolysis. Rabbit bioassay studies showed MYL-1501D and EU-approved insulin glargine are highly similar to US-licensed insulin glargine. These product quality studies show high similarity between MYL-1501D and licensed or approved insulin glargine products and suggest the potential of MYL-1501D as an alternative cost-effective treatment option for patients and clinicians.