Metformin and Type 2 Diabetes

Gunda Siska, PharmD, has worked in various fields within the pharmaceutical industry as a licensed pharmacist for more than 20 years. She is currently a staff hospital pharmacist assisting nurses and doctors with drug prescribing, administration, and dispensing, as well as independently monitoring and dosing highly toxic and dangerous drugs. For 2 years, she was concurrently a consultant pharmacist for skilled nursing facilities and nursing homes. Dr. Siska is a member of the New Mexico Society of Health-System Pharmacists and the American Academy of Anti-Aging Medicine. Follow her on Twitter @GundaSiska

Metformin is a medication that I believe is underappreciated by the general public. Many people ttell me that their doctor prescribed this drug for them, but they took themselves off of it, but if they knew what I know about metformin, they would have stayed on the medication.

This is what I know: metformin extends life. It’s been proven in animal studies1 and in humans. A prospective observational study of nearly 20,000 people with type 2 diabetes mellitus (T2DM) and arteriosclerosis found that metformin use was associated with 24% lower all-cause mortality compared to patients who were not taking metformin.2

It is also the number one go-to medication for type 2 diabetes for several years, despite all the new designer medications coming on the market trying to replace it.

How does metformin save lives? Mainly through cardioprotection. Metformin reduces cardiovascular risk in humans.3  Most people with T2DM will most likely die from a cardiovascular event, especially if they are not on metformin.4,5,6

Metformin has so many positive effects on the body, no one really knows for sure all the ways it preserves life. It produces modest weight loss in the near term5 and blunts weight gain when given chronically.It normalizes hypertension,7 improves heart failure,8 preserves the kidneys,9 improves lipid levels,10 reduces the reoccurrence of colonic polyps and is being used experimentally in several different types of cancers.11 It reduces occurrence of strokes and atrial fibrillation.12,13 It helps in neurodegenerative diseases.14 There is no end to the life-preserving effects of this drug.

Why are so many people taking themselves off of metformin? Because it causes diarrhea. About 10% of metformin users get diarrhea. It’s the type of diarrhea that usually goes a way with time. It is often alleviated when the dose is slowly tapered up, when given in the delayed release form, and/or when taken with food.

It has recently been discovered that just like the newer diabetic medications, metformin also has activity in the gut to lower blood sugar.15 Thirty percent of metformin is excreted unchanged in the feces. It never even enters the bloodstream. It has activity in the lower gastrointestinal tract to produce satiety though a feedback mechanism to reduce consumption of food and ultimately sugar. Then it may have other activities to inhibit absorption of excess sugar into the blood stream. Then it regulates the liver and inhibits it from producing excess sugar through gluconeogenisis. Then once the sugar is actually in the bloodstream, metformin reverses insulin resistance, allowing the blood sugar to enter the cell and be used efficiently.

The medical experts at the National Institute on Aging, compare the longevity effects of metformin to calorie restriction. Both theories involve the way our bodies use energy.

When cells are no longer inundated with glucose and constantly being forcsfed, they wake up, become alive and vibrantly healthy.

The opposite is true. When we overeat chronically, our cells are forcefed glucose. Insulin resistance occurs as a result of protecting the internal cell functions from being overloaded with glucose. The cells shut down and are no longer as receptive to receiving new energy into the cell. It’s similar to a wooden stove being continually overloaded with wood. It cannot function properly under those circumstances and the door to the stove becomes difficult to open. The wood is analogous to glucose. The man opening the door is analogous to insulin. The stove door is analogous to the insulin receptor.

I tell all my patients that eating until we are 80% full is key to a healthy metabolism. I’m a strict advocate of this practice myself. But in reality, I know many people cannot accomplish this goal long term. Fortunately for drugs like metformin, people who are not as disciplined and motivated can still have a long healthy life. I wish the best for my patients, that is why I highly recommend that they take the medications that their doctors prescribe in addition to diet and exercise.


1. Martin-Montalvo A, Mercken EM Mitchell SJ, et al. Metformin improves health span and lifespan in mice. Nature Comm. 2013. doi; 10.1038/ncomms3192.

2. Roussel R, Travert F, Pasquet B, et al. Metformin use and mortality among patients with diabetes and atherlosclerosis. Arch Intern Med. 2010;170:1892–1899.

3.) Home PD. Impact of the UKPDS--an overview. Diabetic Med. 2008;25(suppl 2):2–8.

4.) Gu K, Cowie CC, Harris MI. Mortality in adults with and without diabetes in a national cohort of the US population, 1971–1993. Diabetes Care. 1998;21:1138–1145.

5.) UK Prospective Diabetes Study (UKPDS) Group. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes. Lancet. 1998;352:854–865.

6.) Holman R, Paul S, Bethel M, Matthews D, Neil H. 10-year follow-up of intensive glucose control in type 2 diabetes. N Engl J Med. 2008;359:1577–1589.

7.) Landin K, Tengborn L, Smith U. Treating insulin resistance in hypertension with metformin reduces both blood pressure and metabolic risk factors. J Intern Med. 1991;229:181–187.

8.) Roumie CL, Greevy RA, Grijalva CG, et al. Association between intensification of metformin treatment with insulin vs sulfonylureas and cardiovascular events and all-cause mortality among patients with diabetes. JAMA. 2014;311:2288–2296.

9.) Hung, SC, et al. Metformin use and mortality in patients with advanced chronic kidney disease: national, retrospective, observational, cohort study.  Lancet Diab Endocrinol. 3(8):605–614.

10.) Roumie CL, Huizinga MM, Liu X, et al. The effect of incident antidiabetic regimens on lipid profiles in veterans with type 2 diabetes: a retrospective cohort. Pharmacoepidemiol Drug Saf. 2011;20:36.

11.) Metformin Active in Reducing Colorectal Polyp Recurrence. Higurashi T, Hosono K, Takahashi H, et al. Metformin for chemoprevention of metachronous colorectaladenoma or polyps in post-polypectomy patients without diabetes: a multicentre double-blind, placebo-controlled, randomised phase 3 trial. Lancet Oncol. 2016;17:475-483.

12.) Cheng YY, Leu HB, Chen TJ, et al. Metformin-inclusive therapy reduces the risk of stroke in patients with diabetes: a 4-year follow-up study. J Stroke Cerebrovasc Dis. 2014;23:e99-e105.

13.) Chang SH, Wu LS, Chiou MJ, et al. Association of metformin with lower atrial fibrillation risk among patients with type 2 diabetes mellitus: a population-based dynamic cohort and in vitro studies. Cardiovasc Diabetol. 2014;13:123.

14.) Metformin Linked to Lower Neurodegenerative Disease Risk. American Diabetes Association 2016 Scientific Sessions; June 11, 2016; New Orleans, Louisiana. Abstract 72-OR/72.

15.)  Buse JB, DeFronzo RA, Rosenstock J, et al. The Primary Glucose-Lowering Effect of Metformin Resides in the Gut, Not the Circulation. Diabetes Care. 2016;39(2):198-205.