Metformin: 10 Things You Should Know
Medically reviewed on Apr 22, 2018 by L. Anderson, PharmD
Metformin is a Workhorse for Type 2 Diabetes
Metformin, also known by the brand names:
- Glucophage XR
and others, and has been available for the oral treatment of type 2 diabetes since 1995.
Metformin helps to control blood sugar (glucose) levels and is sometimes used in combination with insulin or other medications.
Metformin is a true workhorse for diabetics: a 2017 study published in Diabetes Care showed that the number of people who started metformin as their first treatment has increased since 2005, while sulfonylureas, another popular diabetes treatment, remained the most popular second-line agent. In fact, metformin is recommended in guidelines as the first-line drug treatment for new patients, along with diet and exercise.
Metformin is Truly Lifesaving
We know that starting type 2 diabetes treatment with metformin helps to prevent the need for additional diabetes medications in the long-term. But what else does it do?
A study from the Annals of Internal Medicine demonstrated that starting diabetes treatment with metformin is also linked with a lower long-term risk of:
- heart attack
- and death
than starting with a sulfonylurea, like glyburide or glipizide.
However, researchers can't say whether the difference is due to extra risk from sulfonylurea drugs, added benefits from metformin, or both.
Diabetes is Expensive but Metformin is Affordable
There are several different strengths of metformin, too. It may be that instead of taking the 1,000 mg (milligram) tablet of metformin per dose you could take two 500 mg tablets and save money.
Always ask for the least costly version of generic metformin, as some generics may be more expensive.
If at any time you feel like you cannot afford your medications, have a frank discussion with your doctor or pharmacist to look at other options.
Free samples, discount coupons, and even a switch to a more affordable drug class may be possible.
Insulin Resistance and the A1C
There are many forces at work when a patient is diagnosed with type 2 diabetes.
Insulin resistance is one of them, where the hormone insulin is not used effectively and too much sugar is left in the blood. Metformin works to make the body's cells more sensitive to insulin and decreases the amount of sugar naturally produced in the liver.
Guidelines from the American Diabetes Association (ADA) state that blood sugar levels should be targeted to the individual patient. Blood glucose targets (A1C) are individualized based on:
- duration of diabetes
- age/life expectancy
- comorbid conditions
- known CVD or advanced microvascular complications
- hypoglycemia unawareness
- individual patient considerations.
While metformin is a recommended first-line therapy, some patients may need to be started on a second drug at the same time to reach blood sugar goals.
The ADA suggests that the A1C measurement should be less than 7% for most nonpregnant adults with diabetes. However, more or less stringent glycemic goals may be appropriate for each individual.
In March 2018, the American College of Physicians (ACP) relaxed their recommendations on target A1C levels, suggesting that A1C should be between 7 and 8 percent for most adults with type 2 diabetes. For adults who achieve an A1C below 6.5 percent, the group suggests stepping down diabetes treatment to keep that level from going even lower. The ADA was not in complete agreement with these recommendations.
Can't You Smell That Smell?
Pharmacists and patients are well aware that metformin may come with a fishy smell when you open the bottle. The smell does not mean the drug is spoiled, it's just due to it's inherent characteristics.
Metformin is associated with relatively few side effects, but nausea may be one of them, possibly due to this 'fishy' odor.
According to a report published in the Annals of Internal Medicine, some extended-release forms of metformin have a lower odor, and may be less likely to cause nausea. If you can't tolerate your metformin, let your doctor know. A switch to the extended-release form or a different manufacturer may do the trick.
Hypoglycemia: A Smaller Risk, But Still There
Hypoglycemia, or excessively low blood sugar, can occur due to the use of many diabetes medications.
One advantage of metformin is its low risk of causing hypoglycemia in only about 1% to 10% of patients. However, if someone has not eaten adequately, plays in strenuous sports without eating, or is also taking other other glucose-lowering agents such as sulfonylureas or insulin, hypoglycemia can set in.
Drinking alcohol with metformin can also lead to low blood sugar. Elderly or malnourished patients, and those with adrenal or pituitary insufficiency are especially at risk for low blood sugar.
Lactic Acidosis: A Rare Side Effect
A serious side effect called 'lactic acidosis' is listed in the patient education sheet for metformin. It's important you know about it, but it's also important you realize it's a very rare side effect.
Lactic acidosis is a build-up of lactic acid in your blood due to low oxygen levels. Lactic acidosis can occur in people with severe kidney or liver disease. According to the manufacturer, metformin can be used in mild to moderate kidney disease with an eGFR (estimated GFR) greater than 45 mL/min/1.73 m2. Metformin use is contraindicated (should not be used) in patients with severe renal impairment (eGFR below 30 mL/min/1.73 m2).
Besides kidney disease, other conditions that may predispose patients to lactic acidosis, and where metformin use is contraindicated, include:
- liver disease
- alcohol abuse, binge drinking
- acute heart failure
- have surgery
- age 65 or greater
- radiologic studies with contrast
- a past history of lactic acidosis during metformin therapy
- certain drug interactions
- hypoxic states (a lack of oxygen reaching the tissues) • have a heart attack, severe infection, or stroke
Lactic acidosis has been reported in about one in 33,000 patients taking metformin over one year. Although rare, if lactic acidosis does occur, it can be fatal in up to half the people who develop it.
A 2018 case report outlines a 54-year old woman taking metformin who presents with lactic acidosis to the emergency department. A Naranjo assessment score of 8 was obtained, which indicates a probable relationship linking the lactic acidosis with metformin use.
What Are the Signs of Lactic Acidosis?
If you take metformin, have your electrolyte levels checked 1 to 2 weeks after starting treatment.
Signs of lactic acidosis include:
- Feeling very weak or tired
- Unusual muscle pain or weakness
- Trouble breathing
- Stomach discomfort, nausea, vomiting
- Feeling cold
- Feeling dizzy
- Suddenly developing a slow or irregular heartbeat
If you notice any of these signs, stop taking metformin and call your doctor right away.
Will Metformin Help Me Lose Weight?
Many people with type 2 diabetes have insulin resistance and need to lose weight. Of course, for anyone, the best way to lose weight is gradually through a combination of a healthy diet and daily exercise.
However, large studies have looked at weight loss in patients taking metformin, and weight loss is variable. In some studies, patients have lost from 4 to 6.5 pounds (lbs.), while in other studies, they've only about 2 lbs. However, weight loss does seem to be the norm, even if only a slight weight loss, in contrast to the weight gain that often occurs with insulin or sulfonylurea treatment.
In general, while metformin is a useful drug to control blood sugar in diabetes, weight loss due to metformin alone may not be enough. Patients should use an appropriate diet and regular exercise for weight control in type 2 diabetes.
How Should I Take Metformin?
Metformin comes in a regular-release and extended-release tablets in varying strengths. Metformin is usually taken with a meal. It may be taken twice a day, but some forms of metformin are taken only once daily.
Metformin can cause stomach upset, nausea or diarrhea at the beginning of treatment, but for many people these effects will subside over time. Taking with a meal can help to minimize stomach upset and diarrhea.
To also help lessen these reactions and determine the most effective dose, your doctor will start you on a low dose and gradually increase it over time. In adults, the maximum daily dose of regular-release metformin is 2550 mg and the maximum daily dose of extended-release metformin is 2000 mg.
PCOS: An Off-Label Use for Metformin
Polycystic ovary syndrome (PCOS) is a disorder in which an imbalance of sex hormones can cause changes in the menstrual cycle, ovarian cysts, trouble getting pregnant, acne, facial hair growth, insulin resistance and other health problems. PCOS affects 5 to 15 percent of women of childbearing age, and they may have elevated diabetes risk and heart disease risk throughout life.
Metformin is one treatment used "off-label" to treat PCOS. Your doctor may prescribe diabetes medicines that reduce insulin resistance. Several medicines used to treat type 2 diabetes, including metformin (Glucophage), can decrease testosterone levels, restore normal menstrual cycles and restore fertility.
Finished: Metformin: 10 Things You Should Know
- Umeda T, Minami T, Bartolomei K, et al. Metformin-Associated Lactic Acidosis: A Case Report. Drug Saf Case Rep. 2018 Feb 9;5(1):8. doi: 10.1007/s40800-018-0076-1. Accessed April 22, 2018 at https://www.ncbi.nlm.nih.gov/pubmed/29427160
- Salpeter SR, Greyber E, Pasternak GA, et al. Risk of fatal and nonfatal lactic acidosis with metformin use in type 2 diabetes mellitus. Cochrane Database Syst Rev. 2010 Apr 14;(4):CD002967. Accessed April 22, 2018 at https://www.ncbi.nlm.nih.gov/pubmed?term=20393934
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