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The progressive nature of Type 2 diabetes necessitates treatment intensification over time in order to maintain glycaemic control, with many patients ultimately requiring insulin therapy. While insulin has unlimited potential efficacy, its initiation is often delayed and improvements in glycaemic control are typically accompanied by weight gain and an increased risk of hypoglycaemia, particularly as HbA1c approaches and falls below target levels. This may account for the sub-optimal control often achieved after insulin initiation. Combining insulin with antihyperglycaemic therapies that have a low risk of hypoglycaemia and are weight-neutral or result in weight loss is a therapeutic strategy with the potential to improve Type 2 diabetes management. Although the effects differ with each individual class of therapy, clinical trials have shown that adding a glucagon-like peptide-1 receptor agonist, dipeptidyl peptidase-4 inhibitor or sodium-glucose co-transporter-2 inhibitor to insulin regimens can offer a significant reduction in HbA1c without substantially increasing hypoglycaemia risk, or weight. The evidence and merit of each approach are reviewed in this paper. Once-daily co-formulations of a basal insulin and a glucagon-like peptide-1 receptor agonist have been developed (insulin degludec/liraglutide) or are under development (lixisenatide/insulin glargine). Insulin degludec/liraglutide phase III trials and a lixisenatide/insulin glargine phase II trial have shown robust HbA1c reductions, with weight loss and a low risk of hypoglycaemia. With insulin degludec/liraglutide now approved in Europe, an important consideration will be the types of patients who may benefit most from a fixed-ratio combination; this is discussed in the present review, and we also take a look toward future developments in the field. [ABSTRACT FROM AUTHOR]

Objectives Current British HIV Association ( BHIVA) guidelines recommend that all patients with a CD4 count <350 cells/μ L are offered highly active antiretroviral therapy ( HAART). We identified risk factors for delayed initiation of HAART following a CD4 count <350 cells/μ L. Methods All adults under follow-up in 2008 who had a first confirmed CD4 count <350 cells/μ L from 2004 to 2008, who had not initiated treatment and who had >6 months of follow-up were included in the study. Characteristics at the time of the low CD4 cell count and over follow-up were compared to identify factors associated with delayed HAART uptake. Analyses used proportional hazards regression with fixed (sex/risk group, age, ethnicity, AIDS, baseline CD4 cell count and calendar year) and time-updated (frequency of CD4 cell count measurement, proportion of CD4 counts <350 cells/μ L, latest CD4 cell count, CD4 percentage and viral load) covariates. Results Of 4871 patients with a confirmed low CD4 cell count, 436 (8.9%) remained untreated. In multivariable analyses, those starting HAART were older [adjusted relative hazard ( aRH)/10 years 1.15], were more likely to be female heterosexual ( aRH 1.13), were more likely to have had AIDS ( aRH 1.14), had a greater number of CD4 measurements < 350 cells/μ L ( aRH/additional count 1.18), had a lower CD4 count over follow-up ( aRH/50 cells/μ L higher 0.57), had a lower CD4 percentage ( aRH/5% higher 0.90) and had a higher viral load ( aRH/log10 HIV-1 RNA copies/ml higher 1.06). Injecting drug users ( aRH 0.53), women infected with HIV via nonsexual or injecting drug use routes ( aRH 0.75) and those of unknown ethnicity ( aRH 0.69) were less likely to commence HAART. Conclusion A substantial minority of patients with a CD4 count < 350 cells/μ L remain untreated despite its indication. [ABSTRACT FROM AUTHOR]