Thank you for your insightful posts Dr. Rami Abunadar. Do you have any thoughts/potential suggestions why Acarbose and Canagliflozing resulted in an increase in lifespan in male rodents, but not in females?
There is no definitive answer to this, Only some theories. What I sense from your question is that you’re worried that perhaps Acarbose may not confer benefit to you as a female similar to what happened in the mice studies.
Mice after all aren’t exactly like humans. It’s difficult to say what might perfectly transfer and what might not. We’re not even 100% certain sure that any of the ITP studies and effects will actually translate to humans, Nevermind exact sex-specific differences.
But what i do know is there has been over two decades of studies and research on the beneficial effects of Acarbose in humans on cardiovascular disease, Cancer, Incidence of diabetes, Overall mortality…etc. Yet never came across a paper which said or hinted that the benefits only show in males.
There a genetic mutation present in some people that affect the SGLT1 receptors in the gut, Which decreases the post-meal glucose spike throughout their lives, similar to acarbose. This study found that for every 20mg/dl decrease in glucose spike (Which is less large of a decrease than what acarbose might produce). They had 50% less likelihood to die, Develop diabetes and obesity. There was no mention of this effect being only male-specific
So I encourage both males and females to take acarbose based on the available evidence. This is subject to change if some definitive form of evidence emerged against this, Which there isn’t any at the moment. I convinced my wife to start taking acarbose.
Dr. Rami,
Whenever I check urine glucose while taking empagliflozin (non-diabetic), it is very positive for glucose.
I see the data above, but I don’t understand why .
Even if the initial postprandial blood glucose peak is unaffected, why wouldn’t the area of the curve be decreased since glucose disposal should be faster due to the combined effect of disposal into the urine added with disposal into muscle, liver, etc? Any ideas? Thanks
Also, the studies mentioned previously are the acute effects of SGLT2 inhibition postprandially. I’d speculate that regular use of SGLT2 by a non-diabetic would increase insulin sensitivity over time (via visceral fat reduction?), which in turn would lead to improved chronic glucose control/disposal.
My guess is that in healthy people the peak and the shape of the glucose curve are mostly controlled by the rate of absorption from the gut. SGLT inhibitors which dump glucose into urine, Or drugs like metformin that increase insulin sensitivity will certainly help in decreasing both the peak and AUC of insulin since the pancreas will require less insulin to be secreted by definition, But it won’t necessarily affect the glucose peak or even curve.
The rationale being (At least I suspect) is that when there is less glucose to deal with (as with SGLTI) or it’s easier for tissues to take up glucose (Metformin), The pancreas will simply compensate by secreting less insulin. Hence there will be no change in glucose peak or even AUC perhaps, However, there will be a change in insulin peak and AUC.
Acarbose mechanism in the ITP was most likely due to affecting peak glucose and not simply increased insulin sensitivity. It’s important to remember that metformin which is quite effective in improving insulin sensitivity, Failed to increase lifespan in mice in the ITP studies.
The idea behind my post is to point out that SGLI is not a substitute for Acarbose if one hopes of replicating the ITP studies. Not that SGLI aren’t useful in humans.
I believe that any insulin-sensitizing drugs like SGLTI or metformin will be useful in humans in some form or shape. And if the person is convinced of their benefits based on solid research and understanding of their short and long-term side effects., Then they can choose to take it along with acarbose.
