Modelling energy intake (3): empagliflozin

In the aftermath of the of canfliglozin post I picked up this paper via Tucker:

Energy Balance After Sodium–Glucose Cotransporter 2 Inhibition

It's the group including Hall again, with a different drug but still looking at glycosuria as an "insensible" caloric loss. If you feed the daily glucose loss in to their sophisticated CICO derived formula the weight loss over 90 weeks should be 11.3kg whereas the actual weight loss was 3.2kg.

This was correctly attributed to increased calorie intake, reverse modelled to an increase of calories in the region of 270kcal/day. What to do about this?

The best section of the abstract is the conclusion, which sums up the paper:

"Chronic glycosuria elicits an adaptive increase in energy intake. Combining SGLT2 inhibition with caloric restriction is expected to be associated with major weight loss."

Translation, "starve the buggers". Starvation ALWAYS facilitates "major weight loss".

That was 2015. But even then Hall was well aware of the stupidity of this approach, as he detailed in his 2016 publication:

How strongly does appetite counter weight loss? Quantification of the feedback control of human energy intake

If caloric restriction where a feasible option I guess no one would ever get fat and, if they did, anyone could easily lose weight by caloric restriction, without the risk of fungal necrotising fasciitis (necessitating emergency removal of significant parts of a person's genitalia and possibly surrounding tissues) which comes as a real risk with the canagliflozin or empagliflozin deal. Sadly caloric restriction is generally associated with intolerable hunger and rapidly failing ability to maintain any large caloric restriction. An insight superbly documented Hall et al.

Ultimately in the real world of the CIM, the urinary loss of "x" glucose calories drops insulin. It appears that this drop in insulin releases a certain amount of FFAs from adipocytes, say "y" kcal, but y is never quite enough to fully compensate for the urinary loss x (no reason it should be). So a small amount of food is needed to make up the deficit as perceived by the brain stem. Back in 2015 I guess diabetics were being advised to eat low fat, high carbohydrate diets. So each patient eats a few extra calories, roughly x minus y extra. That food will be around 55% carbohydrate. Which will directly offset the urinary loss per se but more importantly, will increment the level of insulin in the bloodstream.

As insulin is incremented upwards by the extra food, so FFA release from adipocytes will increment downwards and so a spiral of rising food intake, rising insulin and falling FFAs (limiting weight loss) will ensue.

There is some sustained weight loss. I would guess that this is related to the residual fat content of the extra food eaten, which won't raise insulin the way the carbohydrate component will.

Which leaves you wondering if by providing the small food increment needed to off set the x - y deficit in the form of fat, perhaps a much more significant weight loss might have occurred. Not sure 11.3kg would be possible, but it might be.

And of course starvation would not be needed... But perhaps that smacks of LC eating and the CIM too much.

Peter