Drug listing recommendations from health technology assessment (HTA) agencies often fail to coincide with one another. We conducted a comparative analysis of listing recommendations in Australia (PBAC), the Netherlands (CVZ), Sweden (TLV) and the UK (NICE) over time, examined interagency agreement, and explored how process-related factors-including time delay between HTA evaluations, therapeutic indication and orphan drug status, measure of health economic value, and comparator-impacted decision-making in drug coverage. Agreement was poor to moderate across HTA agency listing recommendations, yet it increased as the delay between HTA agency appraisals decreased, when orphan drugs were assessed, and when low-value medicines (immunosuppressants, antineoplastics) were removed from the sample. International differences in drug listing recommendations seem to occur in part due to inconsistencies in how the supporting evidence informs assessment, but also to differences in how domestic priorities shape the value-based decision-making process.

AimsGlucagon-like peptide-1 (GLP-1) receptor agonists and dipeptidyl peptidase-4 (DPP4) inhibitors improve glucose tolerance by still incompletely understood mechanisms. Each class of antihyperglycemic drugs has also been proposed to increase pancreatitis risk. Here, we compare systematically the effects of two widely-used GLP-1 analogues, liraglutide and exendin-4, and the DPP4 inhibitor, sitagliptin, in the mouse.MethodsC57BL6 mice were maintained for 131 days on a normal diet (ND) or a diet comprising 60% fat (HFD) before measurements of fasting blood glucose and insulin, and intraperitoneal glucose tolerance. Beta- and alpha- cell volume, and Reg3b immunoreactivity, were measured by immunohistochemical analysis of pancreatic slices.ResultsWhereas liraglutide (200 µg/kg) and exendin-4 (10 µg/kg) treatment reduced body weight and/or improved glucose tolerance, sitagliptin (10 mg/kg) was without effect on either parameter. Liraglutide caused a sharp reduction in beta-cell mass in both ND and HFD mice, whereas exendin-4 exerted no effect. By contrast, sitagliptin unmasked an action of high fat diet to increase beta-cell mass. Reg3B positive area was augmented by all three agents in normal chow-fed mice, whilst sitagliptin and exendin-4, but not liraglutide, affected this parameter in HFD animals. Correspondingly sitagliptin, but not the GLP-1 analogues, increased circulating amylase levels in ND and HFD mice.ConclusionsLiraglutide improves glucose tolerance in the mouse whilst exerting relatively modest effects on pancreatitis risk. Conversely, exendin-4 and sitagliptin, at doses which exert, respectively, minor or no effects on metabolic parameters, lead to signs of pancreatitis.

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