Today's Reserlogix corporate update was well-timed and occured a couple hours prior to the big LEADER trial announcement (see below) at American Diabetes Association (ADA). There is a lot of attention paid to therapies aimed at cardiovascular disease (CVD) risk reduction in patients with type 2 diabetes (T2D). Resverlogix/Norman Wong presented a poster at ADA on Saturday. Some may question the utility of Resverlogix attending scientific meetings, but it is very important for them to maintain their presence. They might be outshined right now by these other therapies on the market (or soon to be), but if BETonMACE does what the ASSURE/SUSTAIN post-hoc analyses suggest then RVX-208/apabetalone will be the new benchmark. We used to think that CETP inhibitors were the competitors, but if anacetrapib fails to reduce CVD events in REVEAL, their day is done. Here's a summary of the current competitors: SGLT2 inhibitors and GLP-1 Receptor Agonists.

In September 2015 at the EASD meeting, the EMPA-REG OUTCOME trial in patients with T2D and high CVD risk showed that the sodium/glucose cotransporter 2 (SGLT2) inhibitor Empagliflozin (Jardiance) significantly reduced 3-point MACE (cardiovascular death, non-fatal myocardial infarction (MI), non-fatal stroke) by 14%. The event rate was 12.1% in the placebo group and 10.5% in the Empagliflozin group. This 14% reduction was almost exclusively due to a 38% reduction in cardivascular death. Non-fatal MI was reported in 5.2% of patients in the placebo group and 4.5% of those in the empagliflozin group (13% reduction), and non-fatal stroke in 2.6% of placebo patients and 3.2% of empagliflozin patients (24% increase), respectively. However, these differences in non-fatal MI and stroke were not significant. This result was well received and hailed the first therapy for patients with T2D to not only offer glucose control but to lower CVD risk. Empagliflozin is already approved for use.

Today, at the ADA meeting the LEADER trial in patients with T2D with high CVD risk showed that the glucagon-like-peptide-1 (GLP-1) receptor agonist Liraglutide (Victoza) significantly reduced the same 3-point MACE metric by 13%. The event rate was 14.9% in the placebo group and 13% in the Liraglutide group. This 13% reduction was primarly due to a 22% reduction in cardiovascular death. There was also a 12% reduction in non-fatal MI (6.8% in placebo, 6.0% in Liraglutide group) and 11% reduction in non-fatal stroke (3.8% in placebo, 3.4% in Liraglutide group). However, these differences in non-fatal MI and stroke were not significant. These results were also well received and hailed another addition to the T2D management pharmacological toolkit to offer glucose control AND lower CVD risk. Liraglutide is already approved for use.

Shortly after Novo Nordisk announced their top-line LEADER trial results earlier in Spring 2016, they also announced top-line results of thier SUSTAIN-6 trial with another GLP-1 receptor agonist called Semaglutide in patients with T2D. The primary endpoint was the same 3-point MACE metric as described above. According to the press statement, "The trial achieved its primary end point of showing noninferiority of major cardiovascular events (MACE) with semaglutide compared with placebo, as well as a statistically significant reduction in cardiovascular risk." Novo Nordisk plans to present the full results of SUSTAIN-6 at an upcoming meeting, but not at this weeks ADA meeting. This will make two GLP-1 receptor agonists (both from Novo Nordisk) to achieve MACE reduction and glucose control in patients with T2D. Semaglutide is not yet approved for use.

Also at ADA this week, Merck/Pfizer presented glucose-lowering data for their SGLT2 inhibitor Ertugliflozin, and are underway with a cardiovascular outcomes trial. Here's a Seeking Alpha article summarizing the findings. This won't read out until 2020, but if successful to reduce MACE would add a second SGLT2 inhibitor to reduce CVD risk and provide glucose control in patients with T2D. Ertugliglozin is not yet approved for use.