The burgeoning crisis of type 2 diabetes (T2D) has imposed a severe strain on the healthcare resources of de- veloping countries such as Jordan [1] . In 2012, Jordan reported a diabetes prevalence of 8.73% [2] . Data from the national Behavioural Risk Factor Surveillance System in 2004 [3] disclosed an increased prevalence of dia- betes risk factors, such as obesity, and a high proportion of participants with undiagnosed diabetes. Also, an analysis involving 917 T2D patients in Jordan revealed that poor glycaemic control was chiefly linked to the long duration of T2D and lack of adherence to recommended self-care behaviours [4] . Indeed, improving T2D awareness and treatment adherence of patients are among the prime goals of T2D management in Jordan.

International treatment guidelines [5] recommend maintaining glycated haemoglobin A_1c (HbA_1c) levels at <7.0%, fasting plasma glucose (FPG) at <130 mg/dL and postprandial plasma glucose (PPPG) at <180 mg/dL to avoid the risk of incurring long-term diabetic complications. Physicians are further advised to appropriately intensify therapeutic regimens to maintain blood glucose at the recommended levels [5] . However, inadequate monitoring of disease progression and concerns about hypoglycaemia, injections and weight gain may inhibit patients and physicians from following these recommendations. Even so, T2D patients will eventually require supplementation of both basal and prandial insulin owing to the gradual loss of beta-cell function [6] . Premixed insulins, constituting a mixture of rapid-acting insulin with a basal version, were developed to help remedy the endogenous insulin deficit.

Biphasic insulin aspart 30 (BIAsp 30) is a premixed insulin analogue consisting of 70% protaminated insulin aspart (IAsp) and 30% rapid-acting IAsp [7] . The longer-acting protaminated component addresses basal insulin requirements and rapid-acting IAsp addresses the prandial insulin deficit. BIAsp 30 therapy is associated with low incidences of major and nocturnal hypoglycaemia [8] [9] and is known to effectively reduce high blood glucose [10] .

Often, healthcare policy design and implementation is hampered by a dearth of local clinical data. Observational studies, such as A₁chieve, conducted across 28 countries [11] , could provide a key pool of data that can aid in informing local policies and clinical practice guidelines.

The A₁chieve study was non-interventional in nature and aimed to gather information on the safety and effectiveness of insulin analogues in routine healthcare in different countries. This Jordanian sub-analysis aimed to document the safety and effectiveness of BIAsp 30 therapy in local practice and also to examine the current status of T2D management in Jordan.

This sub-analysis showed that BIAsp 30 therapy was well-tolerated in Jordanian patients with T2D and was associated with significant reductions of hyperglycaemia in both insulin-naïve and insulin-experienced patients over 24 weeks. Poor glycaemic control was apparent in the entire subgroup at baseline (mean HbA_1c, 9.8%; FPG, 205.0 mg/dL; PPPG, 292.1 mg/dL). Even patients previously treated with other insulins for approximately 3 years had average HbA_1c levels of 9.1% at baseline. These results are consistent with baseline findings from the overall A₁chieve cohort that also revealed high levels of blood glucose (mean HbA_1c, 9.5%) [11] .

The incidence of major hypoglycaemia reduced from baseline to Week 24 in the entire Jordanian subgroup, with significantly fewer patients reporting major hypoglycaemic events after 24 weeks of BIAsp 30 therapy. The increased incidence of overall hypoglycaemia noted in the entire subgroup was primarily caused by an increase in the proportion of insulin-naïve patients reporting minor and nocturnal hypoglycaemic events. The proportion of insulin-naïve patients that reported minor hypoglycaemia also increased significantly from baseline to Week 24 in the overall A₁chieve cohort on BIAsp 30 therapy [11] .

Fasting and postprandial glucose levels reduced markedly in the Jordanian subgroup following 24 weeks’ treatment with BIAsp 30. The reductions in FPG and PPPG were accompanied by reductions in the HbA_1c levels in these Jordanian patients as well, triggering improvements in mean HbA_1c by −2.5% ± 1.3% in insulin-naïve patients and –1.9% ± 1.4% in insulin-experienced patients. Furthermore, 112 patients in the entire subgroup achieved the HbA_1c target level of <7.0% by Week 24 compared to only 6 patients at baseline. These results are particularly noteworthy in the light of findings from the United Kingdom Prospective Diabetes Study that linked a 1% reduction in mean HbA_1c to a 37% risk reduction for microvascular complications and a 14% risk reduc- tion for myocardial infarction [12] .

Hypercholesterolaemia and hypertriglyceridaemia are common co-morbidities for T2D patients. A 2006 study revealed that dyslipidaemia was highly prevalent among Jordanian T2D patients (reported in over 90% of pa- tients) and high LDL cholesterol levels were the most common form (reported in 91.5% of patients) [13] . In this sub-analysis, Jordanian patients presented with high lipid levels at baseline, while at Week 24, significantly lower levels of total cholesterol, LDL cholesterol and triglycerides were observed. The mean SBP also improved by an average of −6.1 ± 16.1 mmHg, suggesting that patients may have initiated lifestyle changes during the study. As expected, mean body weight increased in the entire subgroup, primarily due to an increase (~2.0 kg) in insulin-naïve patients following the start of insulin therapy.

Fluctuating blood glucose levels and the complications associated with T2D can significantly affect patients’ well-being [14] . However, following 24 weeks of BIAsp 30 therapy, patient QoL, assessed using the validated EQ-5D questionnaire, improved noticeably from baseline levels. It is possible that the demonstrated improve- ments in blood glucose and lipid levels and the low incidence of hypoglycaemia may have contributed to the greater positive patient responses at Week 24.

This sub-analysis is subject to certain limitations of the non-interventional design of the A₁chieve study. The study lacked a control arm. Concomitant medication and dietary intake were not controlled and data collection was largely based on patient recall, diaries or self-reported information. The incidence of hypoglycaemia was collected based on the patients’ recall of the past 4 weeks prior to the study visit, which may have led to an un- derestimation of the actual occurrence rate of hypoglycaemic events. Nevertheless, this study provided an op- portunity to evaluate treatment strategies for T2D in routine clinical care in Jordan. The results of this sub- analysis demonstrate the safety and effectiveness of BIAsp 30 in a setting that is close to real life and in a patient group not restricted by strict selection criteria. These results can also provide evidence for framing clinical policies in Jordan. In summation, starting BIAsp 30 therapy improved glycaemic control and was not associated with any issues of tolerability or safety in this Jordanian subgroup.

The authors would like to thank all participants who provided data, and all investigators involved in the A₁chieve study. The authors would like to thank Chunduo Shen of Novo Nordisk for providing statistical analysis. The authors would also like to thank Anjali Philip of Cognizant Technology Solutions for writing assistance, funded by Novo Nordisk.

This study was sponsored by Novo Nordisk. The sponsor took part in the development of the protocol, the process of data collection and analysis, funding of medical writing services, and in reviewing the manuscript, but not in participant selection, choice of therapies (study or otherwise), provision of therapies including insulin or continuing clinical management of the participants.

Jihad Haddad is an advisory board member for Novo Nordisk and Merck, and is on the speaker’s bureau for Novo Nordisk, Merck, Novartis, Astra Zeneca, Merck Sharp & Dohme, and Menarini. Levent Sandalci is em- ployed by Novo Nordisk. Fares H. Haddad, Rashad Nasser, Abdel-Ellah Al-Shudifat, Firas Abbas Annavi and Moawia Al-Kilani have no conflicts of interest to declare.