Analyst notes: Will GLP-1 agonists see earlier use in diabetes?

Intensification of treatment over time is necessary in most diabetic patients due to the progressive nature of the disease with a downward spiral of glycaemic control. Current treatment strategies incorporate oral agents as the first- and second-line options, with glucagon-like peptide-1 (GLP-1) receptor agonists and insulin therapies being largely reserved for later-line settings. The delayed introduction of injectable therapies is, in part, due to clinical inertia and patients' needle phobia associated with injectable therapies. Nevertheless, a number of key opinion leaders (KOLs) interviewed for FirstWord's forthcoming report Type II Diabetes Mellitus: KOL insight think GLP-1s should be initiated earlier in the treatment strategy to gain better glycaemic control at a much earlier stage in the disease progression.

Insights, Analysis & Views

Debatably, GLP-1s are considered to be one of the most potent classes of drugs offering not only effective blood glucose control, but also weight reduction for diabetic patients. Several short-acting (exenatide [Byetta/Bydureon; AstraZeneca] and lixisenatide [Lyxumia; Sanofi]), intermediate-acting (liraglutide, [Victoza; Novo Nordisk]) and long-acting products (albiglutide [Tanzeum; GlaxoSmithKline ], dulaglutide [Trulicity; Eli Lilly]) have been approved. However, once-daily Victoza currently remains the gold-standard in this class. KOLs are highly impressed by Victoza's cardiovascular (CV) outcomes data from the LEADER study, which showed that treatment with the drug reduced the risk of a major adverse CV event (MACE) by 13 percent compared to placebo. The data has led the FDA to approve new labelling for Victoza to include the claim that it lowers the risk of heart attack, stroke and CV-related death.

"I think that now that we've got the LEADER study showing that there are cardiovascular advantages for GLP-1 receptor agonists, and also the fact that we've got the SUSTAIN 6 study, although it's not currently available, showing that semaglutide has cardiovascular advantages, these are all big pluses [for this class]." - EU Key Opinion Leader

Recently, novel GLP-1/basal insulin combinations Xultophy (Novo Nordisk) and Soliqua 100/33 (Sanofi) have also become available on the market. Xultophy is a fixed-ratio combination (FDC) of liraglutide (Victoza) and insulin degludec (Tresiba), whilst the Soliqua 100/33 injection combines insulin glargine (Lantus) with lixisenatide (Adlyxin). Whilst these FDCs show great efficacy, KOLs believe it will take time for these agents to become embedded in the treatment algorithm.

Overall, whilst many experts advocate earlier use of GLP-1s, particularly in obese patients, they stress that the injectable mode of delivery and costs will remain as key barriers for these therapies.

For companies operating in the diabetes market in Europe and the US, Type 2 Diabetes mellitus: KOL Insight is a must read. The report provides actionable insights and commentary on some of the most critical issues in the diabetes market, and provides perspectives on pipeline therapies and how their potential in a rapidly increasing market. The report also discusses how treatment paradigms could change in T2DM. For more information, please click here.

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