What is the strongest medicine for diabetes?

Medication for Type 2 Diabetes

Making lifestyle changes—such as eating healthfully, exercising, and losing weight—is the most effective way to manage type 2 diabetes and prevent complications. If these changes aren’t enough, NYU Langone doctors may recommend medication to control blood sugar levels.

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For some people, one medication may be sufficient to lower blood sugar levels. Others may need a combination of two or more medications. Medications are most effective when combined with lifestyle changes.

Many people with type 2 diabetes need to take medication to control blood sugar levels for the rest of their lives. Sometimes, however, losing weight and improving your overall health may eventually eliminate the need for medication.

Oral Medications

For people with mild to moderate type 2 diabetes, medications taken by mouth are effective in controlling blood sugar levels. Some increase the body’s sensitivity to insulin, also described as decreasing insulin resistance. Others enhance the effects of hormones that help control blood sugar levels.

Biguanides

One commonly prescribed medication for type 2 diabetes is metformin, which belongs to a class of medications known as biguanides. This medication is taken daily by mouth.

The medication makes your liver and muscles more sensitive to insulin and reduces glucose production in the liver. This allows the body to use glucose more efficiently.

In rare instances, metformin can cause mild gastrointestinal symptoms, such as stomach upset and diarrhea. These symptoms can be avoided if the medication is started at a low dosage and is slowly increased.

Sulfonylureas

Doctors commonly prescribe sulfonylurea medications, such as glyburide, glipizide, and others, to lower blood sugar levels in people with type 2 diabetes.

These medications increase insulin production in the pancreas. Sulfonylurea medications are often prescribed in combination with metformin.

Side effects can include hypoglycemia, or low blood sugar levels, and increased hunger and weight gain. Your doctor monitors you carefully in order to avoid these.

Thiazolidinediones

Medications belonging to a class called thiazolidinediones, or glitazones, reverse insulin resistance by improving insulin sensitivity in muscle, liver, and fat cells. They also help prevent the liver from releasing excess glucose.

Taken once daily, glitazones are often prescribed in combination with other medications for type 2 diabetes. Because they increase insulin sensitivity, they may reduce the amount of medication needed to increase insulin production.

These medications can cause fluid retention, which may exacerbate congestive heart failure in people who have that condition. They may also increase the risk of bladder cancer, as well as fractures in people with osteoporosis. Your doctor weighs your risk of these conditions into account when recommending these medications.

Gliptins

Gliptins, also called DPP4 inhibitors, block the action of an enzyme called DDP4. They enhance the effects of a hormone that stimulates insulin production and prevents the liver from releasing too much glucose. Our doctors may prescribe these medications for people who have difficulty controlling blood sugar levels after meals.

Gliptins, taken daily, are prescribed alone or in combination with metformin. These medications are generally well tolerated but may cause hypoglycemia in people who are using them with other medications for type 2 diabetes.

Meglitinides

Meglitinides, also known as glinides, rapidly lower blood sugar levels by stimulating the pancreas to release insulin after meals. These medications are often prescribed for people with moderately high glucose levels. Because meglitinides work rapidly for a short period of time, they’re most effective when taken before meals.

The most common side effect of these medications is hypoglycemia, especially when taken with other medications for type 2 diabetes. Other side effects include headache, nausea, and stomach pain.

Glucosidase Inhibitors

Glucosidase inhibitors, sometimes called “starch blockers,” reduce blood sugar levels by blocking an enzyme called glucosidase. This enzyme helps break down carbohydrates in the small intestine, allowing carbohydrates to release sugar into the bloodstream. These medications help slow the intestine’s absorption of carbohydrates.

Taken at the beginning of meals, glucosidase inhibitors can help prevent a sharp increase in blood sugar levels. When taken with other medications to control blood sugar levels, these medications can cause hypoglycemia. Common side effects include bloating, nausea, diarrhea, and gas.

Gliflozins

Gliflozins, or SGLT2 inhibitors, are a newer class of medications that prevent the kidneys from reabsorbing glucose. The excess sugar is eliminated in the urine.

Gliflozins can be taken alone or in combination with metformin. Common side effects include vaginal yeast infections and urinary tract infections.

Insulin

For people with more severe type 2 diabetes—meaning blood sugar levels that are consistently high—doctors usually prescribe insulin. Insulin is a hormone produced in the pancreas that’s responsible for signaling muscles and other body tissues to use sugar from food.

There are several different kinds of insulin, most of which are given by injection. When injected once a day, long-acting forms of insulin lower glucose levels for up to 24 hours. Short-acting forms, which are injected before meals, lower glucose levels immediately, preventing food from causing a spike in blood sugar levels.

A new short-acting form of insulin comes in a powder that can be inhaled. It’s used before meals, allowing some people to eliminate the need to inject short-acting insulin at mealtimes.

Your doctor decides which type of insulin is best for you based on the severity of your condition.

If insulin doesn’t control diabetes, you may benefit from a gastric bypass procedure, which is a type of weight loss surgery that reduces the size of the stomach.

GLP-1 Agonists

GLP-1 agonists mimic the action of glucagon-like peptide 1, a hormone that helps lower blood sugar levels after meals. These medications help the body release more insulin and prevent the liver from releasing excess glucose after meals. Because they lower blood sugar levels after meals, GLP-1 agonists cannot be taken with short-acting forms of insulin, which have the same effect.

GLP-1 agonists are given via an injection under the skin. Some formulations are given once or twice daily. Long-lasting versions can be used once a week. Some people experience nausea and vomiting when beginning treatment with a GLP-1 agonist.

Glucose Monitoring

Your doctor may also teach you how to use a glucose monitor, a portable electronic device that uses a small drop of blood to measure your glucose level. It can determine your blood sugar levels in seconds. Regularly monitoring your blood sugar level helps to ensure your medication is working as it should.

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Understanding medicine — Type 2 diabetes

Most people need medicine to control their type 2 diabetes.

This helps keep your blood sugar level as normal as possible to prevent health problems.

You may have to take it for the rest of your life, although your medicine or dose may need to change over time.

Adjusting your diet and being active is usually also necessary to keep your blood sugar level down.

Medicines for type 2 diabetes

There are many types of medicine for type 2 diabetes. It can take time to find a medicine and dose that’s right for you.

You’ll usually be offered a medicine called metformin first.

You may need to take extra medicines, or a different medicine such as insulin, if:

• treatment is not keeping your blood sugar levels within a healthy range
• you have heart problems or need to lose weight

Your GP or diabetes nurse will recommend the medicines most suitable for you.

Your medicine might not make you feel any different, but this does not mean it’s not working. It’s important to keep taking it to help prevent future health problems.

Metformin

Metformin is the most common medicine for type 2 diabetes. It can help keep your blood sugar at a healthy level.

It comes as tablets you take with or after meals.

Common side effects of metformin include feeling or being sick and diarrhoea. If this happens to you, your doctor may suggest trying a different type called slow-release metformin.

Other diabetes medicines

If metformin does not work well enough on its own, you cannot take it or you have other health problems, you may need to take other medicines alongside or instead of metformin.

• other tablets that help lower your blood sugar, such as gliclazide, glimepiride, alogliptin, linagliptin or pioglitazone
• tablets that lower your blood sugar and help your heart pump blood around your body, such as dapagliflozin or empagliflozin
• injections that lower your blood sugar and help you lose weight, such as exenatide or liraglutide

Insulin

You’ll need insulin if other medicines no longer work well enough to keep your blood sugar within a healthy range.

Sometimes you may need insulin for a short time, such as if you’re pregnant, if you’re ill, or to bring your blood sugar level down when you’re first diagnosed.

You inject insulin using an insulin pen. This is a device that helps you inject safely and take the right dose.

Using an insulin pen does not usually hurt. The needles are very small, as you only inject a small amount just under your skin. Your diabetes nurse will show you where to inject and how to use your pen.

Your GP or diabetes specialist will recommend the type of insulin treatment that’s best for you.

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Side effects

Your diabetes medicine may cause side effects, but most people do not get any.

The side effects you may get depend on which medicines you’re taking.

Do not stop taking your medicine if you get side effects. Talk to your doctor, who may suggest trying a different medicine.

Low blood sugar (hypos)

Some diabetes medicines can cause low blood sugar, known as hypoglycaemia or hypos.

If you take medicine that can cause hypos, your doctor might recommend that you check your blood sugar regularly. You’ll be given a testing kit and shown how to do a finger-prick test.

If you take insulin at least twice a day and have frequent or severe hypos, you might also be offered a continuous glucose monitor (CGM) or flash monitor.

This is a small sensor you wear on your skin that lets you check your blood sugar level at any time.

How to get free prescriptions for diabetes medicine

If you take diabetes medicine, you’re entitled to free prescriptions for all your medicines.

To claim your free prescriptions, you’ll need to apply for an exemption certificate. This is known as a PF57 form.

• fill in a form at your GP surgery
• you should get the certificate in the post about a week later – it’ll last for 5 years
• take it to your pharmacy with your prescriptions

Save your receipts if you have to pay for diabetes medicine before you receive your exemption certificate. You can claim the money back if you include the receipts along with your completed PF57 form.

Travelling with diabetes medicines

If you’re going on holiday:

• pack extra medicine – speak to your diabetes nurse about how much to take
• carry your medicine in your hand luggage just in case checked-in bags go missing or get damaged
• if you’re flying with a medicine you inject, get a letter from your GP that says you need it to treat diabetes

Page last reviewed: 18 August 2020
Next review due: 18 August 2023

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Breaking down diabetes: Drugs for diabetes, starting with the best — metformin

Metformin is physician-researcher Randall Stafford’s go-to drug for diabetes. He explains why in this installment in the series, Breaking down diabetes.

Author Randall Stafford Published on November 18, 2020 November 18, 2020

Editors’ note: We are revising two posts in the Breaking Down Diabetes series to reflect current findings on the most effective medications. The best place to begin the series is with the first post, On the road to diabetes: A look at what’s happening inside the body. A huge assortment of 100 medications are available to treat high blood sugar in Type 2 diabetes, including two historical breakthrough drugs, insulin and metformin. The pharmaceutical industry has successfully added a few new, innovative drugs, but the most effective drugs remain the older, less expensive medications. Let’s make some sense out of this mess of medications. Most are given by mouth (oral), but injected insulin, which I’ll address in a future blog post, remains a key medication. In addition, oral drugs have limited impact, so they are often used in combinations (including tablets containing two drugs). Patients frequently try multiple oral drugs before starting insulin.

Metformin is my go-to drug

With very few exceptions, I start patients on metformin first. To illustrate a patient’s experience with diabetes drugs, let’s check in on with Mrs. R., a 70-year-old with diabetes:

When she was first diagnosed 19 years ago, she started on metformin at 500 mg twice per day. These large tablets initially caused intestinal discomfort (a common side effect). Over time, the mild abdominal pain went away. This drug worked well for a few years, but Mrs. R gained some additional weight and the metformin was no longer adequate. The drug, glipizide was added. This also worked for many years, but in 2012, she needed a third drug, sitagliptin. Eventually, she would need insulin.

To understand Mrs. R’s experience, or the medications taken by you or a friend or family member, let’s start with the best medication, metformin. Approved by the U.S. Food & Drug Administration in 1994, metformin is so critical to diabetes treatment that if you don’t tolerate it at first because of abdominal side effects, it’s worth trying again. Many of my patients who did not tolerate this drug at first did better when they started at low doses and then worked to increase the amount they could easily tolerate. This is my first-line, go-to drug for diabetes, and I’m always surprised when I encounter a patient with Type 2 diabetes who’s not taking it. And, just to be clear, metformin is a generic and I have no financial interests related to its use. Interestingly, the origin of metformin can be traced back to a herbal remedy from French lilac that has been known since the Middle Ages.

Why metformin works

• It can help with weight loss, while nearly all other diabetes drugs cause weight gain.
• Metformin reduces high blood sugar, but rarely lowers blood sugar to levels below normal. Most other drugs have the potential to cause life-threatening hypoglycemia (low blood sugar).
• This drug can be continued even if it becomes necessary to start insulin.
• It’s inexpensive, costing pharmacies as little as $0.06 per day of treatment.

Metformin works by increasing the body’s response to insulin, effectively reversing the insulin resistance that causes Type 2 diabetes. Insulin resistance occurs when the body’s liver, muscle and fat cells require more and more insulin in the bloodstream to make them do their jobs.

It’s no surprise that it is widely used, with 72% of U.S. diabetes patients who take medications on metformin. It could be used even more often. If you have Type 2 diabetes, you need to be on metformin or have a good reason not to take it (like advanced kidney disease). If you’ve tried it and have had indigestion or other abdominal problems, it may be worth trying this wonder drug again.

There are six other major classes of blood-sugar lowering drugs used in Type 2 diabetes. Of these, the SGLT2 inhibitors (short for sodium-glucose co-transporter) are emerging as the next best drug after metformin. All of these medications can be combined with metformin to get blood sugar back towards normal levels. We will review these next-best drugs in the next blog post.

Randall Stafford, MD, PhD, a professor of medicine and director of the Program on Prevention Outcomes and Practices, practices primary care internal medicine at Stanford. He is developing practical strategies to improve how physicians and consumers approach chronic disease treatment and prevention.

This is the sixth piece in the series, «Breaking Down Diabetes,» created for those with or at risk for diabetes as well as their family and friends. Previous blog posts addressed the pre-diabetes, diabetes complications, and goals for diabetes beyond blood sugar. Some data for this report come from IQVIA, Inc., previously known as QuintilesIMS. For additional information, please contact rstaff@stanford.edu.