How can metformin inhibit gluconeogenesis without causing hypoglycemia

Factual Questions
1

If you’re in a fasted state and your body can’t perform gluconeogenesis properly, wouldn’t this lead to low blood sugar?

2

The usual answer given is that metformin does not stimulate insulin secretion. This means that if glucose levels fall in a metformin user, so too will insulin levels. As insulin falls, the breaks are taken off gluconeogenesis, glycogenolysis, and glucagon secretion with the net result being that hypoglycemia is prevented, i.e. the effect of metformin to inhibit hepatic gluconeogenesis is offset by the many other compensatory responses to incipient hypoglycemia.

But the real answer is that the mechanism of action of metformin is still not well understood. For example, it has significant effects on intestinal metabolism and the implication of these on glucose and lactate metabolism are just beginning to be unraveled.

3

I have been told that metformin (which I have been taking since 2005) cannot lead to hypoglycemia. One of the side-effects was to lose 20 pounds in the first year I started without any attempt at dieting.

4

In addition to inhibiting hepatic gluconeogenesis, metformin also appears to help prevent dementia/cognitive decline.

Studies indicate metformin helps protect against cognitive decline in diabetics and pre-diabetics. Further studies are needed to conclude if it also helps protect non-diabetics.

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5

Metformin possibly has general anti-aging principles that need to be investigated.

I’m just unsure how a drug that blocks gluconeogenesis could avoid causing hypoglycemia. Maybe its like KarlGauss said, when your sugars drop your body does maneuvers that overwhelm the drugs inhibitory effects on gluconeogenesis.

6

Metformin also shows some promise in inhibiting some breast cancers.

7

60 pounds for me in the first year. It required effort and attention but wasn’t at all difficult. Happy to report that 5 years later (at age 70) I’ve regained only 10 of the lost pounds.

8

Glad to hear it. About five years later I started actually dieting again and lost another 40 pounds and have stayed within a five pound range ever since.

9

Glad for your success as well. And same here - After regaining the ten pounds (about 4 years after the 60# loss), my body apparently adopted a new “set point” and ever since I’ve been up five, down five, over and over … I’m quite comfortable with it.