In exciting news for patients, Janssen just announced the initiation of the CREDENCE phase 3 trial, which will investigate the SGLT-2 inhibitor Invokana's (canagliflozin) effect on renal outcomes in type 2 diabetes patients with mild to moderate renal impairment. We very much admire Janssen's commitment to tackling long-term diabetes complications, for which there continues to be an incredible shortage of treatment options. Some may be surprised to learn of this trial given that Invokana's phase 3 data suggested a slight transient worsening in eGFR in patients with moderate renal impairment and limited glycemic efficacy in this population. We spoke today with Dr. Norman Rosenthal, canagliflozin compound development team leader at Janssen, who hypothesized that canagliflozin could conceivably have a direct mechanistic effect on the kidney independent of glycemic control (and instead related to, perhaps, reducing hyperfiltration and glomerular strain) - we learned that the company saw an impressive ~50% improvement in urinary albumin/creatinine ratios in the phase 3 sub-population with mild to moderate renal impairment. While CREDENCE is not expected to complete until 2019, if results are positive then the implications could be profound: to date no other drug has definitively shown a benefit on improving long-term diabetes outcomes. If Invokana's CV profile comes out clean in CANVAS (and there is no reason it shouldn't), then a composite profile including weight loss, blood-pressure lowering, oral administration AND improved renal outcomes would be extremely compelling and, we imagine, may even (best case scenario) propel SGLT-2 inhibitors into the first-line position (or at least a higher position that current SGLT-2s have). We'll be back soon with our full report, which will contain more thoughts on the implications of this trial (e.g., in relation to the CANVAS CVOT and CANVAS-R long-term renal endpoint study), as well as more from our very interesting interview with the very smart Dr. Rosenthal.