This question is for people who have a good grasp of the physiological disease-process of diabetes. It is well-known that Metformin helps diabetics who take it lose weight. That's certainly one major reason I am very fond of it myself. The diabetes book I'm reading says that it does this by reducing the appetite, but I certainly haven't experienced any reduction in appetite that I can discern. So I tend to think that the weight-loss effect is likely something related to the main thing the medication does physiologically. And what it does is inhibit the glycogenolysis effect (breaking down stored glycogen into usable glucose in the liver) of glucagon (the yin to insulin's yang).
My understanding is that insulin and glucagon have a negative feedback relationship (glucose-levels going up triggers the release of insulin, which brings glucose-levels down, and this in turn triggers the release of glucagon, which raises glucose-levels, thereby maintaining balance). So as glucagon promotes the release of stored energy (through lipolysis, or the breakdown of stored fat into usable fatty-acids, as well as through glycogenlysis), so also does insulin promote energy storage. (That's why if you have been overweight your entire life, then pre-diabetic insulin-resistance will likely give you a nice, big beachball on your lower-middle front torso to carry around with you!) What really gets me about insulin's promotion of energy storage is that it not only promotes the conversion of fatty acids into stored fat and the conversion of glucose into stored glycogen, it also promotes the conversion of glucose into stored fat when the glycogen capacity of the muscles and the liver is full. GUH! ARGH!
So my educated speculation about why Metformin promotes weight-loss is that the effect of the glucagon is inhibited, so the body produces less insulin because there isn't the need for as much insulin to make muscle-cells able to use glucose as energy. And this is simply because less glucose is being released form storage in the liver. The result of this change in the nature of the balance is that less fat is stored. This is the only thing that really makes sense to me when I think about it, but the problem with my supposition is that the glucose-insulin metabolism is out-of-whack in diabetes, and that could affect things in ways that I'm just not yet understanding. So if I'm all wet here, then definitely give me some schooling in why I'm all wet. Inquiring minds want to know!
ETA: If I'm right about this "less insulin" stuff, then that might possibly mean that Metformin also slows down the wearing out from overuse of the beta-cells in the pancreas that produce insulin, thereby lengthening the period of time that one can produce just barely enough (though still not enough to be "normal") of one's own insulin provided one does all the right things WRT lifestyle.
My understanding is that insulin and glucagon have a negative feedback relationship (glucose-levels going up triggers the release of insulin, which brings glucose-levels down, and this in turn triggers the release of glucagon, which raises glucose-levels, thereby maintaining balance). So as glucagon promotes the release of stored energy (through lipolysis, or the breakdown of stored fat into usable fatty-acids, as well as through glycogenlysis), so also does insulin promote energy storage. (That's why if you have been overweight your entire life, then pre-diabetic insulin-resistance will likely give you a nice, big beachball on your lower-middle front torso to carry around with you!) What really gets me about insulin's promotion of energy storage is that it not only promotes the conversion of fatty acids into stored fat and the conversion of glucose into stored glycogen, it also promotes the conversion of glucose into stored fat when the glycogen capacity of the muscles and the liver is full. GUH! ARGH!
So my educated speculation about why Metformin promotes weight-loss is that the effect of the glucagon is inhibited, so the body produces less insulin because there isn't the need for as much insulin to make muscle-cells able to use glucose as energy. And this is simply because less glucose is being released form storage in the liver. The result of this change in the nature of the balance is that less fat is stored. This is the only thing that really makes sense to me when I think about it, but the problem with my supposition is that the glucose-insulin metabolism is out-of-whack in diabetes, and that could affect things in ways that I'm just not yet understanding. So if I'm all wet here, then definitely give me some schooling in why I'm all wet. Inquiring minds want to know!
ETA: If I'm right about this "less insulin" stuff, then that might possibly mean that Metformin also slows down the wearing out from overuse of the beta-cells in the pancreas that produce insulin, thereby lengthening the period of time that one can produce just barely enough (though still not enough to be "normal") of one's own insulin provided one does all the right things WRT lifestyle.