On 2017 Aug 20, NephJC - Nephrology Journal Club commented:

The exciting paper “Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes” was discussed on June 27th and 28th 2017 on #NephJC, the open online nephrology journal club.

Introductory comments written by Swapnil Hiremath are available at the NephJC website here

Nearly 200 people participated in the discussion with over 1000 tweets. One of the authors, Vlado Perkovic also kindly joined the journal club

The highlights of the tweetchat were:

• There has been very heterogenous use of SGLT2 inhibitors (SGLT2i) across the globe to date. They tend to be more commonly started by endocrinologists. There have been some cases of euglycemic DKA noted.

• The studies were felt to be well-designed followed FDA guidance for non-inferiority meticulously. According to the authors, unexpected effects made it difficult to proceed to larger study without understanding cardiovascular safety in detail – hence CANVAS-R.

• It was unusual that such a high percentage (70%) of the group had normoalbuminuria.

• It would be interesting to determine what weight loss was calorific and what was diuretic effect.

• The excess of amputations and fractures in the canagliflozin group was surprising. Postulated mechanisms for this included expression of SGLT2i elsewhere in the body and differential effects on oxidative phosphorylation.

• Overall there were promising composite renal endpoints but there is still some concern about the potential adverse events revealed here which time may better delineate the extent of.

Transcripts of the tweetchats, and curated versions as storify are available from the NephJC website.

Interested individuals can track and join in the conversation by following @NephJC or #NephJC on twitter, liking @NephJC on facebook, signing up for the mailing list, or just visit the webpage at NephJC.com.

On 2017 Jun 18, Thomas Heston commented:

This trial basically shows that treating diabetes helps decrease cardiovascular morbidity, which is not a new finding. To determine if canagliflozin has a unique property in decreasing cardiovascular events beyond simply lowering blood sugar, the analysis would have had to match patients by their hemoglobin A1c, then compare outcomes of placebo vs canagliflozin. Amazingly, this was not done. They did not look at cardiovascular events after correcting for hemoglobin A1c levels. Note that this was a pharmaceutical company funded research project, and the conclusion heavily implies that canagliflozin (as opposed to any agent that lowers blood sugar) has a unique quality of lowering cardiovascular events in diabetics. The authors did not prove that canagliflozin had any unique cardiovascular protective properties [Heston TF, 2017]. By not separating out the potential unique effects of canagliflozin beyond just lowering blood sugar, the results regarding a unique cardiovascular effect are basically meaningless and even worse, misleading.

On 2017 Jun 18, Thomas Heston commented:

This trial basically shows that treating diabetes helps decrease cardiovascular morbidity, which is not a new finding. To determine if canagliflozin has a unique property in decreasing cardiovascular events beyond simply lowering blood sugar, the analysis would have had to match patients by their hemoglobin A1c, then compare outcomes of placebo vs canagliflozin. Amazingly, this was not done. They did not look at cardiovascular events after correcting for hemoglobin A1c levels. Note that this was a pharmaceutical company funded research project, and the conclusion heavily implies that canagliflozin (as opposed to any agent that lowers blood sugar) has a unique quality of lowering cardiovascular events in diabetics. The authors did not prove that canagliflozin had any unique cardiovascular protective properties [Heston TF, 2017]. By not separating out the potential unique effects of canagliflozin beyond just lowering blood sugar, the results regarding a unique cardiovascular effect are basically meaningless and even worse, misleading.

On 2017 Aug 20, NephJC - Nephrology Journal Club commented:

The exciting paper “Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes” was discussed on June 27th and 28th 2017 on #NephJC, the open online nephrology journal club.

Introductory comments written by Swapnil Hiremath are available at the NephJC website here

Nearly 200 people participated in the discussion with over 1000 tweets. One of the authors, Vlado Perkovic also kindly joined the journal club

The highlights of the tweetchat were:

• There has been very heterogenous use of SGLT2 inhibitors (SGLT2i) across the globe to date. They tend to be more commonly started by endocrinologists. There have been some cases of euglycemic DKA noted.

• The studies were felt to be well-designed followed FDA guidance for non-inferiority meticulously. According to the authors, unexpected effects made it difficult to proceed to larger study without understanding cardiovascular safety in detail – hence CANVAS-R.

• It was unusual that such a high percentage (70%) of the group had normoalbuminuria.

• It would be interesting to determine what weight loss was calorific and what was diuretic effect.

• The excess of amputations and fractures in the canagliflozin group was surprising. Postulated mechanisms for this included expression of SGLT2i elsewhere in the body and differential effects on oxidative phosphorylation.

• Overall there were promising composite renal endpoints but there is still some concern about the potential adverse events revealed here which time may better delineate the extent of.

Transcripts of the tweetchats, and curated versions as storify are available from the NephJC website.

Interested individuals can track and join in the conversation by following @NephJC or #NephJC on twitter, liking @NephJC on facebook, signing up for the mailing list, or just visit the webpage at NephJC.com.