Metformin for weight loss

[The_Skeptic]

I've been reading reports that taking the diabetic drug Metformin, even if you don't have diabetes, can help you lose weight.

Does anyone have any experience with this?

http://bit.ly/aBaydQ

 

[Michael Scally MD]

I've been reading reports that taking the diabetic drug Metformin, even if you don't have diabetes, can help you lose weight.

Does anyone have any experience with this?

http://bit.ly/aBaydQ

Yes. True.

 

[cvictorg]

Yes. True.

But what will the effect on your blood sugar levels be?

 

[Michael Scally MD]

But what will the effect on your blood sugar levels be?

Nada.

Mechanism of Action

Metformin is an antihyperglycemic agent which improves glucose tolerance in patients with type 2 diabetes, lowering both basal and postprandial plasma glucose. Its pharmacologic mechanisms of action are different from other classes of oral antihyperglycemic agents. Metformin decreases hepatic glucose production, decreases intestinal absorption of glucose, and improves insulin sensitivity by increasing peripheral glucose uptake and utilization. Unlike sulfonylureas, metformin does not produce hypoglycemia in either patients with type 2 diabetes or normal subjects (except in special circumstances, see PRECAUTIONS) and does not cause hyperinsulinemia. With metformin therapy, insulin secretion remains unchanged while fasting insulin levels and day-long plasma insulin response may actually decrease. http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?id=18054

 

[CubbieBlue]

So how come somebody hasn't resold glucophage as fatfade and made a million bucks yet?

 

[Michael Scally MD]

So how come somebody hasn't resold glucophage as fatfade and made a million bucks yet?

I did not say it was significantly effective. From my recall, it is marginally effective and not all that consistent except in pre-diabetes. It might be of benefit as a step in obesity management.

 

[Millard]

Some history of its use in bodybuilding community...

Bodybuilders experimented with this back in the mid- to late-90s. Dan Duchaine wrote about it in Muscle Media 2000 Oct 1996:

Yes, we have now discovered that for nondiabetic bodybuilders, the high dosage of 1,800 mg of metformin (Glucophage) a day is effective. The estimates for phenformin have been that it’s from five to ten times more potent, on a milligram-per-milligram comparison.

I’ve found that using one 25-mg tablet 6 times a day, usually before meals, seems to instill a similar pump and vascularity to the 1,800-mg dosage of metformin. This is a total dosage of 150 mg of phenformin, which is near the 10 times greater potency predicted. If you used the timereleased 50-mg Debeone capsule available in Mexico, you’d need only 3 capsules a day.
.

But he seemed to abandon it the following year as bodybuilders weren't too excited by the results (may 1997 MM2K):

Metformin was heralded, a few years back, as an "alternative to insulin," but neither type II diabetics nor bodybuilders have been raving about this drug, What little positive effect met-formin has on insulin resistance occurs only at high dosages. We now have hopes for the next generation diabetic drug, Rezulin (Troglitazone }, recently available here in the States. Since Rezulin's action appears to work on the insulin receptors (increasing their number) and not at the gut level like metformin, it looks like a possible bodybuilding drug. Increasing insulin receptors is a good thing, unless it hap*pens on fat cells, too.

Rezulin seemed to replace it for a lot of bodybuilders, they experimented with insulin, with growth hormone looking for some synergy :

Using Growth Hormone? One New Drug May Make It More Effective

Of course, Rezulin was removed from the market a couple of years later:

F.D.A. Withdraws Drug for Diabetics, Citing Health Risks - New York Times

 

[Millard]

Two popular bodybuilding experts, Jerry Brainum and Lyle McDonald, add to conversation about metformin on facebook. Follow my facebook to follow these fragmented discussions from MESO:

I think there are several other things to consider with metformin. The drug that Duchaine recommended, phenformin, was removed from the market because of a serious possible side effect called lactic acidosis. Metformin works by promoting AMPK, which acts like an energy sensor in the body. When activated, AMPK does promote greater fat oxidation, but it also blunts muscle protein synthesis. In addition, some studies show that metformin in high doses many interfere with testosterone synthesis. On the flip side, animals provided with metformin live longer, thought to be due to better glucose control. Also, emerging studies show that metformin provides a significant protective effect against cancer onset, particularly lung and pancreatic cancers.The way it does this is by interfering with the activity of mTOR, which also happens to be a key player in muscle protein synthesis.

Metformin will cause muscle loss by chronic AMPk activation

 

[Michael Scally MD]

The fascinating story leading to current interest in the use of metformin for cancer prevention and treatment began in medieval Europe. Herbalists of that time recognized that polyuria (excessive urination) could occasionally be alleviated by Galega officinalis (French lilac). Nothing was known concerning the active ingredient of the plant. Even the disease responsible for polyuria which responded to G. officinalis, diabetes mellitus, had not been defined. In the modern era, active fractions of the natural product were identified, leading to drug development efforts. After several false starts, the biguanides metformin, phenformin, and buformin were developed. Clinical experience showed that metformin has an excellent therapeutic index for diabetes, for which the drug was introduced in Europe in the 1970s and approved in the United States in 1995.

Clinical trials showed that metformin has advantages over other agents used in the management of type II diabetes. This finding, in conjunction with the global diabetes epidemic, has made metformin one of the most frequently prescribed drugs on the planet, with an estimated 40 million prescriptions filled in the United States alone in 2008. Its safety has allowed further clinical trials, which documented effectiveness in other conditions including weight gain induced by antipsychotic medications, polycystic ovary disease, and diabetes prevention for subjects at a high risk. Early laboratory studies of biguanides explored antimicrobial activity, and biguanide derivatives are now widely used in applications ranging from swimming pool decontamination to contact lens sterilization and are under study for AIDS treatment. This review outlines the basis for current interest in potential applications of biguanides in oncology.


Pollak M. Metformin and Other Biguanides in Oncology: Advancing the Research Agenda. Cancer Prevention Research 2010;3(9):1060-5.

Retrospective studies that may be impractical to confirm prospectively suggest that diabetics treated with metformin have a substantially reduced cancer burden compared with other diabetics. It is unclear if this reflects a chemopreventive effect, an effect on transformed cells, or both. It also remains to be established if these data have relevance to people without diabetes. Laboratory models, however, provide independent impressive evidence for the activity of metformin and other biguanides in both cancer treatment and chemoprevention. Investigations of mechanisms of action of biguanides have revealed considerable complexity and have identified important gaps in knowledge that should be addressed to ensure the optimal design of clinical trials of these agents. Such trials may define important new indications for biguanides in the prevention and/or treatment of many common cancers.

 

[Michael Scally MD]

Towler MC, Hardie DG. AMP-Activated Protein Kinase in Metabolic Control and Insulin Signaling. Circ Res 2007;100(3):328-41. AMP-Activated Protein Kinase in Metabolic Control and Insulin Signaling -- Towler and Hardie 100 (3): 328 -- Circulation Research

The AMP-activated protein kinase (AMPK) system acts as a sensor of cellular energy status that is conserved in all eukaryotic cells. It is activated by increases in the cellular AMP:ATP ratio caused by metabolic stresses that either interfere with ATP production (eg, deprivation for glucose or oxygen) or that accelerate ATP consumption (eg, muscle contraction). Activation in response to increases in AMP involves phosphorylation by an upstream kinase, the tumor suppressor LKB1. In certain cells (eg, neurones, endothelial cells, and lymphocytes), AMPK can also be activated by a Ca2+-dependent and AMP-independent process involving phosphorylation by an alternate upstream kinase, CaMKK{beta}. Once activated, AMPK switches on catabolic pathways that generate ATP, while switching off ATP-consuming processes such as biosynthesis and cell growth and proliferation. The AMPK complex contains 3 subunits, with the {alpha} subunit being catalytic, the {beta} subunit containing a glycogen-sensing domain, and the {gamma} subunits containing 2 regulatory sites that bind the activating and inhibitory nucleotides AMP and ATP. Although it may have evolved to respond to metabolic stress at the cellular level, hormones and cytokines such as insulin, leptin, and adiponectin can interact with the system, and it now appears to play a key role in maintaining energy balance at the whole body level. The AMPK system may be partly responsible for the health benefits of exercise and is the target for the antidiabetic drug metformin. It is a key player in the development of new treatments for obesity, type 2 diabetes, and the metabolic syndrome.

 

[BBC3]

I tried this once or twice to try to expedite a little fat. And actually it was not metformin but a newer one/same action method. There is an incidence of issues with lactic acid related. And slight straign on kidneys. I actually felt the lactic acid build up a little stronger and longer than normal on one of the 2 week stints I tried it. Overall, it seemed like bullshit, and I have no idea how it could help a diabetic in any way.. Also, it always seems to be tied to complications in older folks who take it for diabetes, at least seems always in the mix whenever I hear about a kodger havin hospital troubs... Probably someone really treaked out fit might be able to get something out of it, if they are already down to counting decimal percentages of body fat reduction... Else I dont know..

 

[AnTabolic73]

Bump.

Any new findings?