GLP-1 Agonists vs. SGLT2 Inhibitors: 6 Differences Between These Diabetes Medications

There are many treatments available for people living with Type 2 diabetes. While many people start with metformin, it’s not always enough on its own. Thankfully, there are still dozens of options beyond metformin. Two to consider are glucagon-like peptide-1 (GLP-1) agonists and sodium-glucose cotransporter-2 (SGLT2) inhibitors.

GLP-1 agonists and SGLT2 inhibitors are two classes of diabetes medications that have grown in popularity over the past decade. While they’re both expert-recommended treatment options, they have several differences. And these distinctions help your diabetes care team pick the one that’s right for you.

Below, we’ll detail six notable differences to consider when comparing GLP-1 agonists versus SGLT2 inhibitors.

1. Most GLP-1 agonists are injections, while SGLT2 inhibitors are available as oral pills

One of the most obvious differences between these classes is their available dosage forms. Most GLP-1 agonists come as injections you give to yourself at home. The frequency of injections varies between individual medications. Some of the most well-known GLP-1 agonists, such as Ozempic (semaglutide), are injected once a week.

All currently available SGLT2 inhibitors come as oral pills that you take once a day. Some people feel more comfortable taking a pill compared to giving themselves a shot. And that’s OK if you feel this way. Just make sure your healthcare professional knows if you have a preference. They’ll take this into account when selecting a medication to prescribe.

Good to know: Rybelsus (semaglutide) and Wegovy tablets (oral semaglutide) are GLP-1 agonist pills. They might be options your prescriber considers if they’d rather you take a GLP-1 agonist but you’d prefer an oral medication.

2. GLP-1 agonists and SGLT2 inhibitors work differently for diabetes

How GLP-1 agonists and SGLT2 inhibitors work for diabetes is another major difference. Both can help lower blood glucose (blood sugar) and hemoglobin A1C (HbA1c or A1C) — your average sugar over the past 3 months. But they do this in different ways.

GLP-1 agonists act like the gut hormone GLP-1 that’s naturally found in your body. They work to lower sugar by:

• Signaling your pancreas to release insulin after you eat

• Helping your body use its natural insulin better

• Telling your liver to make less new sugar

• Slowing down how quickly food leaves your stomach

SGLT2 inhibitors block the actions of the protein SGLT2. They lower sugar levels by preventing the body from reabsorbing sugar through the kidneys. This extra sugar is then removed from the body through your urine (pee).

3. GLP-1 agonists may be better choice if weight loss is one of your health goals

Weight loss with GLP-1 agonists is one of this class’s most well-known effects. In fact, some GLP-1 agonists, such as Wegovy (semaglutide), are FDA approved for chronic weight management. But even those that are only approved for Type 2 diabetes are sometimes prescribed off-label for weight loss.

Because of this, the American Diabetes Association (ADA) recommends GLP-1 agonists if weight loss is one of your diabetes health goals.

Keep in mind that SGLT2 inhibitors do promote moderate weight loss for some people. But not everyone loses weight while taking them. GLP-1 agonists typically cause more significant weight loss.

4. SGLT2 inhibitors may be a better choice if you also have heart failure

It’s common for people with Type 2 diabetes to also have heart failure. If this applies to you, your prescriber may prefer an SGLT2 inhibitor over a GLP-1 agonist.

SGLT2 inhibitors really shine when it comes to their heart failure benefits. This class of medications can take stress off this vital organ. And that can mean a lower risk of hospitalizations and death due to heart failure. Because of this, the ADA recommends SGLT2 inhibitors as a first-choice treatment for people with Type 2 diabetes who also have heart failure.

It's likely that Wegovy (semaglutide) has benefits for people with a type of heart failure called heart failure with preserved ejection fraction (HFpEF). Research suggests the medication can lower the risk of HFpEF-related hospitalizations and death. So it's possible we may see Wegovy approved for HFpEF in the near future.

Good to know: Some SGLT2 inhibitors, such as Jardiance (empagliflozin), are FDA approved to treat heart failure in adults even if you don’t have Type 2 diabetes.

5. Some GLP-1 agonists may lower your A1C more than SGLT2 inhibitors

If A1C-lowering potential is top of mind for your prescriber, they’d likely choose a GLP-1 agonist over an SGLT2 inhibitor. That’s because GLP-1 agonists can lower A1C by as much as 1.5% (up to 2% in some studies). SGLT2 inhibitors reduce A1C by up to 1%.

Keep in mind that your A1C is influenced by many factors, including diet, exercise, and other medications. And you may experience a greater or lesser A1C reduction than what’s discussed here. Combining your medication with healthy lifestyle changes can help you get the most out of your diabetes treatment.

6. GLP-1 agonists and SGLT2 inhibitors have different side effects

GLP-1 agonists and SGLT2 inhibitors also differ in what side effects they typically cause. GLP-1 agonists tend to cause gastrointestinal side effects. SGLT2 inhibitors are more likely to cause urinary-related issues.

Common GLP-1 agonist side effects include:

• Nausea

• Vomiting

• Diarrhea

• Upset stomach

• Constipation

• Gas

• Bloating

Common SGLT2 side effects include:

• Genital yeast infections (more common in women than men)

• Urinary tract infections

• Having to urinate more often

• Nausea

• Constipation

When taken on their own, GLP-1 agonists and SGLT2 inhibitors both have small risks for causing low blood sugar (hypoglycemia). The risk of this serious side effect goes up if you also take insulin, sulfonylureas, or glinides. It’s important to treat hypoglycemia quickly if it happens to you.

Each medication class has more serious side effects to consider before starting one of them. And some medications in a class may have different risks for certain side effects than others. Ask your prescriber for more details on your specific medication.

Can you take a GLP-1 agonist and SGLT2 inhibitor at the same time?

Yes, you can take both a GLP-1 agonist and an SGLT2 inhibitor if needed. These medication classes work differently and can be safely combined. Plus, taking both may provide greater A1C reduction than either could by itself.

But you likely wouldn’t start both a GLP-1 agonist and an SGLT2 inhibitor at the same time. It’s more common to try one class and add another if the first isn’t working well enough by itself. For instance, if you haven’t met your goal A1C level with the highest dosage of Ozempic (a GLP-1 agonist), your prescriber may suggest adding Jardiance (an SGLT2 inhibitor).

How to save on GLP-1 agonists and SGLT2 inhibitors

There are ways to save on GLP-1 agonists and SGLT2 inhibitors. GoodRx can help you navigate your options, including GoodRx discounts, copay savings cards, and patient assistance programs.

By searching your medication’s name on GoodRx’s homepage, you can find details for all the savings opportunities available for it.

If you're new to using GoodRx for semaglutide savings, pay an introductory price for the first two fills: $199 per month for Ozempic or Wegovy injections, or $149 for the Wegovy pill (only available for certain doses). After that, most ongoing fills are $299 or $349 per month, depending on the medication and dose. You can also access Zepbound KwikPen (tirzepatide) through GoodRx starting at $299 per month.

Subscribers to GoodRx for Weight Loss can also access FDA-approved, brand-name GLP-1 medications like Wegovy or Zepbound.

Why trust our experts?

Written by:

Christina Aungst, PharmD

Christina Aungst, PharmD, is a pharmacy editor for GoodRx. She began writing for GoodRx Health in 2019, transitioning from freelance writer to editor in 2021.

Reviewed by:

Stacey McCoy, PharmD, MS, BCPS

Stacey McCoy, PharmD, MS, BCPS, is a clinical pharmacy specialist with over 20 years of experience in various practice areas, including nearly 13 years as an emergency medicine specialist.

Our editorial standards

Meet our experts