I found this an interesting take on metformin. I don’t know if it makes a difference if you are eating very low carbs while taking it but this is Dr. Tom Jelinik, (author of Goodbye Pills
and Needles: A Total Rethink of Type 2 Diabetes And a 90 Day cure) thoughts on this drug for diabetes use.
Sorry it’s kind of long. 
It’s a chapter of this book. (Highly recommend it! )
Problem of Metformin
Metformin is typically the first drug prescribed to a type II diabetic. It used to be marketed under the name Glucophage, which means glucose-eater. And that’s what it does. It makes cells eat glucose, to remove it from the blood. As introduced above, it directly stimulates AMP Kinase, which is supposed to sense cell starvation. Except that metformin stimulates AMP Kinase even when the cell is not starved, but is swimming in excess glucose. One of the problems faced by type II diabetics is fatty liver disease. The liver converts excess carbs to fat too quickly, and some of it builds up as droplets in the liver. Eventually, the fat causes inflammation of the liver, and markers of liver stress appear in the blood. One treatment that seems effective is metformin. This may seem a paradox, at first. Fatty liver is caused by a chronic excess of carbs taken up by the liver, yet it is cured by an agent that makes the liver take up even more. The answer is clear once we realize that glucose uptake is not the relevant factor. It’s true that both insulin and metformin cause glucose uptake, but beyond that, their effects are opposite. Insulin stimulates fat production, while metformin blocks it. Insulin stimulates glycogen synthesis, while metformin also blocks and reverses that. Remember that metformin activates the cell starvation response, which thinks the cell needs energy on an emergency basis. You don’t store glucose as glycogen, or convert it to fat for long-term storage when you’re starving. You use it immediately, for energy right now. Blocking fat production by the liver will give the liver a chance to clear excess fat, which is probably why metformin is effective against fatty liver disease. But what is the liver supposed to do with the excess glucose it is forced to take up, under the false signal that it is starving? It can’t store it. Some gets converted to glucosamine, which accentuates insulin resistance, but metformin bypasses insulin resistance, and continues to stuff the cell with more glucose. The cell starvation response also stimulates glucose fermentation, or glycolysis, to generate energy immediately. So a lot of excess glucose is fermented, and an excess of pyruvate accumulates. Ideally, pyruvate is converted to acetyl-CoA, and enters the citric acid cycle, to make a lot of energy. But the mitochondria can only work so fast. Eventually, there is more fuel than the cell can use. That backs things up, and excess pyruvate is converted to lactic acid. Metformin can occasionally cause a recognized acute condition called lactic acidosis in the liver. You could call that lactic acid poisoning. But what happens at sub-acute levels? A diabetic can be on metformin for twenty years or more, and the drug is not giving cells a good option for what to do with all that glucose, other than turning it into lactic acid. One of the more dubious pieces of medical advice I’ve seen said that diabetes causes chronic fatigue syndrome/ fibromyalgia because cells can’t get enough glucose, and are tired. But as discussed here, cells don’t need insulin to get glucose from blood. Insulin is not even used when energy is needed. It is only used when energy is in surplus, and needs to be stored. Instead, why don’t we ask whether the buildup of lactic acid is responsible for fibromyalgia? There are plenty of reports linking the two, and the widespread use of metformin explains the link perfectly. Given that there are two alternative, and largely contradictory ways to cause GLUT4 movement to the cell surface, which one should be used to treat diabetes? The cell starvation response, or a boosted insulin response? Experienced clinicians already know the answer. Since clearing glucose from circulation is medicine’s only consideration, both are used, often in combination. Yet most of the instructions being given to cells by the combination of metformin and insulin are mutually contradictory. Current practice disregards this fact, and only concerns itself with the blood glucose number, while maintaining a high carbohydrate diet. The cells of a young, healthy person will obey the insulin signal, and shut off the AMP kinase signal. They will then store some amount of glucose as glycogen. But that person is not given metformin. The person prescribed metformin is insulin resistant, so a conflict of signals has to be resolved. How it is resolved depends on the degree of insulin resistance, the dosage of each drug, and the timing of administration. The greater the insulin resistance, and the higher the dose of metformin, the more the balance will favor the cell starvation response, and lactic acid buildup. Elevated glucose in liver cells causes oxidative damage, stress on the liver, and the risk of heart disease may be increased. If this treatment continues for over twenty years, as it often does in the course of diabetes, could this contribute to the high risk of heart disease among diabetics? It’s not on the list of known side-effects for metformin, but let’s not discount the idea. It could be hiding in plain sight; ignored because diabetes itself is considered the cause of heart disease. There’s another lesson in the observation that an intact insulin response shuts off the cell starvation response. Type I diabetics exhibit the symptoms of starvation, in addition to high blood glucose. Type II diabetics, by contrast, are overweight. The difference between them? Insulin. Type I diabetics have only what they inject, where type II diabetics have a chronic excess. We’ll re-visit this several times. Summary: Metformin forces cells to take up glucose, as though the cell were starving. Even when it’s over-stuffed with glucose. Metformin also prohibits cells from storing glucose, or converting it to fat. Glucose can only be burned so fast. What options are left? Intracellular glucose is toxic, so this is a concern.
