Deans' stroke musings: Novel Diabetes Drug Reduces CV Risk

Changing stroke rehab and research worldwide now.Time is Brain! trillions and trillions of neurons that DIE each day because there are NO effective hyperacute therapies besides tPA(only 12% effective). I have 523 posts on hyperacute therapy, enough for researchers to spend decades proving them out. These are my personal ideas and blog on stroke rehabilitation and stroke research. Do not attempt any of these without checking with your medical provider. Unless you join me in agitating, when you need these therapies they won't be there.

What this blog is for:

My blog is not to help survivors recover, it is to have the 10 million yearly stroke survivors light fires underneath their doctors, stroke hospitals and stroke researchers to get stroke solved. 100% recovery. The stroke medical world is completely failing at that goal, they don't even have it as a goal. Shortly after getting out of the hospital and getting NO information on the process or protocols of stroke rehabilitation and recovery I started searching on the internet and found that no other survivor received useful information. This is an attempt to cover all stroke rehabilitation information that should be readily available to survivors so they can talk with informed knowledge to their medical staff. It lays out what needs to be done to get stroke survivors closer to 100% recovery. It's quite disgusting that this information is not available from every stroke association and doctors group.

Monday, September 19, 2016

Novel Diabetes Drug Reduces CV Risk - Semaglutide

Just in case you want to talk to your doctor.
http://www.medpagetoday.com/Cardiology/Prevention/60317?xid=nl_mpt_cardiodaily_2016-09-19&eun=g424561d0r
Major adverse cardiovascular event risk dropped a relative 26% with the novel glucagon-like peptide-1 (GLP-1) analogue semaglutide in high-risk type 2 diabetes patients in SUSTAIN 6, the third such cardiovascular safety outcomes trial to show benefit.
The drug lowered the rate of death from cardiovascular causes, nonfatal MI, or nonfatal stroke to 6.6% compared with 8.9% in the placebo group getting usual care (HR 0.74, 95% CI 0.58-0.95, P<0.001 for noninferiority).
"This lower risk was principally driven by a significant (39%) decrease in the rate of nonfatal stroke and a nonsignificant (26%) decrease in nonfatal MI, with no significant difference in the rate of cardiovascular death," Steven P. Marso, MD, of HCA Midwest Health Research Medical Center in Kansas City, Mo., and colleagues reported.
A number needed to treat for 24 months to prevent one of the primary endpoint events was 45, as reported in the New England Journal of Medicine and at the European Association for the Study of Diabetes in Munich.
Although the trial was not powered for nor had a prespecified analysis to look for superiority of semaglutide, Marso noted to applause at the session that more events than expected occurred and superiority was seen at P=0.02. In that, semaglutide joined a select group agents reporting a cardiovascular outcome benefit.
Last year, the sodium-glucose cotransporter 2 (SGLT2) inhibitor empagliflozin (Jardiance) showed a relative 14% reduction in the same major adverse cardiovascular event (MACE) composite compared with placebo in the EMPA-REG trial, although an FDA advisory panel was split on giving it an indication for reducing risk of cardiovascular mortality. Earlier this year, the GLP-1 drug liraglutide (Victoza) was shown to cut major cardiovascular event rates by 13% in the LEADER trial.
But while both of those trials showed significant reductions in cardiovascular mortality and all-cause mortality as individual endpoints with their respective diabetes drugs, SUSTAIN 6 found no such advantage with semaglutide. Rates of death from cardiovascular causes were similar with the drug as with placebo.
The impact on nonfatal MI, which included silent infarcts, was not statistically significant either (2.9% on semaglutide versus 3.9% on placebo, HR 0.74, P=0.12). But for nonfatal stroke, the difference between semaglutide and placebo was significant (1.6% versus 2.7%, HR 0.61, P=0.04).
The impact on the composite was "meaningful" and "quite substantial," discussant Lars Rydén, MD, PhD, an emeritus professor of cardiology at the Karolinska Institute in Stockholm, told attendees. "We are, in the cardiology field, looking at new platelet-stabilizing drugs and we get much smaller impact on the actual reduction of problems than we are having with that."
He agreed with the researchers that cardiovascular impact of semaglutide might be by delaying or otherwise modifying progression of atherosclerosis.
Even more exciting, Rydén suggested, is the potential for combining both classes that have shown a cardiovascular impact -- GLP-1 and SGLT2 -- "which I think is the most fascinating thought for a new trial."
However, "I don't know if that's going to happen," cautioned Bernard Zinman, MD, of the University of Toronto. Still, he suggested that such findings should heavily influence treatment choices.
"The added value is they reduce cardiovascular death! My God, who ever thought we'd have a diabetes therapy that reduces cardiovascular death?" he told MedPage Today. "We have three trials now with positive outcomes as far as cardiovascular results, so they should be given priority in the algorithm of drugs we would use to treat diabetes."
SUSTAIN 6 included 3,297 patients with type 2 diabetes on a standard diabetes care regimen randomized to once-weekly semaglutide (0.5 mg or 1.0 mg) or placebo for 2.1 years. Among them, 83% qualified for the high-risk criteria by being age 50 or older with established cardiovascular disease and 17% by being age 60 or older with at least one cardiovascular risk factor.
Overall, fewer serious adverse events but more treatment discontinuations (mainly due to GI effects) occurred with semaglutide in a safety profile similar to that of other GLP-1 receptor agonists.
While new or worsening nephropathy was less common with semaglutide, rates of retinopathy complications -- vitreous hemorrhage, blindness, or conditions requiring treatment with an intravitreal agent or photocoagulation -- were significantly and "unexpectedly" higher (HR 1.76, 95% CI 1.11-2.78).
"An association between rapid glucose lowering and worsening of retinopathy has been reported in patients with type 1 diabetes," the researchers noted. "The applicability of such an association to our finding is unclear, and a direct effect of semaglutide cannot be ruled out."
At the session, co-author Tina Visbøll, MD, of the University of Copenhagen, pointed out to continued murmurs of the gathered crowd over this risk that the effect was almost entirely accounted for among patients with pre-existing retinopathy at baseline.
Rydén pointed out that LEADER also showed a 15% relative increase in risk of retinopathy, although not significant with few events.
Pancreatic cancer was actually less common with semaglutide, and pancreatitis rates were similarly low in both groups. No medullary thyroid carcinomas occurred in the trial.
"There's been considerable interest in baseline heart rate for the GLP-1 agonists," Marso noted, and there was an increase that at end of trial was 2.1 and 2.4 bpm over placebo for the lower and higher dose groups, respectively.

The trial was funded by Novo Nordisk.
Marso disclosed relationships with Novo Nordisk, Abbott Vascular, and AstraZeneca.
Rydén disclosed relationships with Amgen, Bayer, Boehringer-Ingelheim, MSD, Sanofi, Merck, Novo Nordisk, the Swedish Heart-Lung Foundation, Swedish Diabetes Foundation, Stockholm County Council, Swedish Medical Assembly, and private donors.
Zinman disclosed relationships with AstraZeneca, Novo Nordisk, Merck, and Lily.