Datamonitor Healthcare attended the 2016 American Heart Association (AHA) Scientific Sessions and brings you the latest news on diabetes research. Analyst Kevin Shannon shares his views on the increasing importance of cardiovascular outcomes in type 2 diabetes studies.
Presenters at the Cardiovascular Outcome Trials (CVOT) in Type 2 Diabetes: Controversies to Consensus session at the 2016 American Heart Association (AHA) Scientific Sessions in New Orleans discussed how recent results from cardiovascular outcomes trials should affect current treatment and regulatory practices. Dr Jacob Udell and Dr Benjamin Scirica debated if dipeptidyl peptidase-IV (DPP-IV) inhibitors will remain a relevant treatment option for type 2 diabetes, considering that sodium-glucose cotransporter-2 (SGLT-2) inhibitors and glucagon-like peptide-1 (GLP-1) agonists have been found to reduce the risk of cardiovascular events in diabetic patients. Additionally, Dr Michael Farkouh and Dr Faiez Zannad discussed if data from these CVOTs support a requirement for pipeline drugs to show a cardiovascular benefit in this patient population in order to gain US Food and Drug Administration (FDA) approval. Strong arguments were presented on both sides, however, most presenters and physicians who attended the session believed that standard treatment and regulatory practices for type 2 diabetes will shift towards therapies with proven cardiovascular benefits.
This potential shift in the type 2 diabetes treatment algorithm is threatening the position of DPP-IV inhibitors in the diabetes market. The DPP-IV inhibitor drug class is one of the most lucrative in type 2 diabetes, with Januvia (sitagliptin; Merck & Co) leading the current market with sales of $3.8bn in 2015. They are typically used in early lines of treatment, soon after patients fail metformin. However, the recent cardiovascular benefits seen with SGLT-2 inhibitors and GLP-1 agonists are causing some physicians to re-evaluate this practice.
Dr Scirica argued that there is no reason to prescribe DPP-IV inhibitors, given the alternative novel treatment options. He cited evidence that there are other non-insulin antidiabetics that are associated with greater glycated hemoglobin (HbA1c) reductions than DPP-IV inhibitors, while also offering a weight loss and potential cardiovascular benefit. Dr Udell countered that the cardiovascular benefits observed with SGLT-2 inhibitor and GLP-1 agonist therapy may have resulted from weight loss alone, citing a meta-analysis of several diabetes CVOTs that reported 1kg in weight loss was associated with a 6% reduction in heart failure risk. However, this argument was not particularly convincing, as it seemed to strengthen the case for therapies that are associated with weight loss in diabetic patients (SGLT-2 inhibitors and GLP-1 agonists).
Moving toward superiority trials for FDA approval may be the most prudent course of action, given strong arguments supporting a shift towards therapies associated with cardiovascular benefits. Dr Farkouh reasoned that pharmaceutical companies should focus on developing novel therapies that further the treatment of type 2 diabetes in order to ensure uptake of their drugs. Dr Zannad countered that non-inferiority trial designs in type 2 diabetes have worked thus far, and argued that there is no need to change the regulatory requirements. However, developing treatments for type 2 diabetes that have neutral cardiovascular outcomes is unlikely to be a successful strategy in the future, given the strong outcomes data for rival drugs that have been presented to date. It may be unsuitable to allow the approval of drugs without a cardiovascular benefit by continuing the FDA’s current requirements for approval.
Physician preferences in type 2 diabetes treatment seem to be shifting toward therapies that have shown a cardiovascular benefit in this patient population. This was reflected in opinions shared both by presenters and attending cardiologists and endocrinologists at AHA 2016. If this shift continues, it is reasonable to expect a significant boost in SGLT-2 and GLP-1 sales at the expense of DPP-IV revenue, along with a possible reassessment of the FDA’s regulatory requirements. However, DPP-IV inhibitors are entrenched in physicians’ current treatment practices. This makes it likely that switching towards therapies showing a cardiovascular benefit may be a slow process for the majority of physicians.