A few CVOTs to keep an eye on at EASD this week and at AHA next month. Some of this I've posted on before, but the more I dig the more I realize is on the horizon.

Harmony Outcomes using GSK's now discontinued (not for safety) GLP1-R agonist albiglutide (Tanzeum). Some previously tested GLP-1R agonists (liraglutide, semaglutide) have shown cardiovascular benefit; other have not (lixisenatide, exenatide). In other GLP1-R agonist CVOT trial news.....The results of Eli Lilly's REWIND trial for Dulaglutide/Trulicity are also expected very soon, potentially late 2018, but as far as I know not at EASD or AHA. So expect GLR-1R agonists to get some headlines in the near term.

CVD-REAL study of the comparative effectiveness on cardiovascular outcomes in new users of SGLT2 inhibitors. This CVD-REAL presenetation at EASD will likely get some headlines, since SLGT2i class, especitally empagliflozin and canagliflozin, have impressed in the EMPA-REG OUTCOMES and CANVASS trials. CVD-REAL is still ongoing and some CVD-REAL data has already been presented/published before. CVD-REAL seems to have different waves/sub-analyses. So there may be some new findings reported at EASD that have not been previously shared. As discussed earlier, the full results for the DECLARE-TIMI CVOT trial for another SGLT2i, dopagliflozin (Farxiga), will be presented at AHA in November. A 4th SGLT2 inhibitor (Merck's ertugliflozin aka STEGLATRO) has an ongoing CVOT (VERTIS-CV) that reads out next year.

Brief Summary from the ClinicalTrials.gov listing for CVD-REAL: CVD-REAL is a multinational, observational cohort study in patients with type 2 diabetes mellitus evaluating the comparative effectiveness of initiating treatment with a sodium-glucose co-transporter-2 (SGLT-2) inhibitor versus another glucose-lowering drug. This study will compare the risk of all-cause mortality and clinically relevant cardiovascular (CV) outcomes respectively in patients who are new users of SGLT-2 inhibitors with those who are new users of other glucose-lowering drugs. CVD-REAL is aiming to collect data from approximately 4 million patients overall, from twelve countries across three major world regions.

CARMELINA: Cardiovascular and Renal Microvascular Outcome Study with the DPP4-inbhibitor Linagliptin in Patients with Type 2 Diabetes Mellitus. Previous DPP4 inhibitors (saxalipitin, alogliptiin, sitagliptin) have failed to show cardiovascular benefit. CARMELINA was previously announced to have met its primary endpoint, so we'll have to wait and see what kind of CVOT RRR effect size gets revealed at EASD this week. CAROLINA, another ongoing CVOT with linagliptin, is also expected to read out results soon, possibly late 2018.

Of course, there's also low-dose methotrexate CIRT at AHA and the purified EPA ehtyl ester REDUCE-IT at AHA. So there will be a lot of buzz about glucose lowering CVOTs, anti-inflammation CVOTs, and triglyceride lowering CVOTs between now and the end of the year.  

By the end of the year, we should have a very clear idea of where the bar has been set and what apabetalone/BETonMACE needs to clear.

BearDownAZ