And I’m Ari Shapiro. Conservatives have been afraid that members of the Republican Party will defect and support Barack Obama, the Democrat. The person they most fear switching sides used to be the most popular member of President Bush’s cabinet, former Secretary of State Colin Powell.

Could the same benefits be translated to those without established CVD (the majority of the patient population we see in clinical practice)? CANVAS PROGRAM was supposed to answer this vital question in addition to assessing CV outcomes in those with established CVD.What was the clinical impact of CANVAS PROGRAM?The only end points in which canagliflozin came out with flying colours were MACE hospitalisation due to heart failure.MACE benefits in only those with established CVD (mimicking EMPA REG trial).No reduction in all cause mortality.No reduction in CV deaths.Significant increase in rates of fractures lower limb amputations.To summarise treating patients with canagliflozin results in:23 fewer MACE (? clinical implication: in the absence of any superiority of the individual end points), 16 fewer hospitalisation due to heart failure, at the cost of 15 more amputations per 1000 patients treated for 5 years (1).Where does that leave us with?In a desperate bid to save the molecule there is an effort to generalise the amputation risk aspect.There is no escaping the fact that the amputation fracture related issue was haunting canagliflozin well before the CANVAS PROGRAM was published (indicated by the black box warnings).What was brought out in the forefront was an EMEA observation of imbalances in the amputation rates in females in the EMPA REG trial (4). Although the EMEA statements were contradictory, they wanted to scrutinise the entire empagliflozin dapagliflozin data before painting this entire class of molecules with the same brush.In July 19th 2017, the entire empagliflozin databank from phase 2 3 EMPA REG were analysed and there was no signal of either increased amputation nor fracture risk (5).Similarly the entire dapagliflozin polled phase 2 3 data did not indicate any adverse signals related to amputation fracture (6).So where do we stand as of now?Empagliflozin remains the gold standard therapy for all type 2 diabetes patients with established CVD with a very reassuring safety profile.Dapagliflozin has also documented its CV safety in polled phase 2 3 trials. Further clarifications will be available after publication oF DECLARE TIMI 58 results.Canagliflozin has MACE benefits but not any CV or all cause mortality benefits and at the cost of increased serious adverse effects.A recent news post from a reputed newspaper quoted a medical regulatory body and suggested that the physicians practicing as “Diabetologist” should be brought under the scanner.

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