Is Jardiance a GLP-1? SGLT2 vs GLP-1 Compared

Jardiance (empagliflozin) is not a GLP-1. It belongs to a completely different drug class called SGLT2 inhibitors. The confusion is understandable because both types of medication are prescribed for type 2 diabetes, both can help with weight and heart health, and both have become household names in recent years. But they work through entirely different mechanisms, carry different side-effect profiles, and have distinct strengths depending on what your doctor is trying to treat.

How SGLT2 Inhibitors Actually Work

SGLT2 inhibitors like Jardiance target a protein in the kidneys called sodium-glucose cotransporter 2. Under normal conditions, your kidneys filter glucose out of the blood and then reabsorb most of it back. SGLT2 inhibitors block that reabsorption step, so glucose is excreted in urine instead of being recycled into the bloodstream. This reduces glucose reabsorption by roughly half to sixty percent.¹ The mechanism is independent of insulin, which is a key distinction. Whether your body produces enough insulin or responds well to it, the drug still works because it acts on the kidneys, not on the pancreas or gut.

Other SGLT2 inhibitors you may have heard of include dapagliflozin (Farxiga) and canagliflozin (Invokana). They all share the same basic mechanism but differ slightly in potency and approved uses. The entire class traces its roots to phlorizin, a compound identified in apple tree bark back in 1835, though it took until the early 2010s for modified versions selective enough for clinical use to reach the market.²

How GLP-1 Receptor Agonists Work

GLP-1 receptor agonists mimic a gut hormone called glucagon-like peptide-1. Normally, your intestines release GLP-1 after you eat, which tells your pancreas to produce more insulin and reduces glucagon (a hormone that raises blood sugar). GLP-1 also slows stomach emptying and signals the brain that you are full. The natural hormone is broken down within minutes, so GLP-1 receptor agonists are engineered versions that last much longer in the body, from hours to a full week depending on the drug.³

The most well-known GLP-1 drugs right now are semaglutide (Ozempic, Wegovy, Rybelsus), liraglutide (Victoza, Saxenda), and tirzepatide (Mounjaro, Zepbound), although tirzepatide actually targets both GLP-1 and another incretin hormone called GIP. The first drug in this class, exenatide, was derived from a compound found in the saliva of the Gila monster lizard, identified in 1992 and approved in 2005.²

So the fundamental difference is where these drugs act. SGLT2 inhibitors work at the kidney to dump excess glucose. GLP-1 receptor agonists work through the pancreas, gut, and brain to regulate insulin, appetite, and digestion. Jardiance does none of the appetite-suppressing or insulin-stimulating things that GLP-1 drugs do.

Blood Sugar Control

Both drug classes lower HbA1c, the standard measure of average blood sugar over the previous two to three months. Head-to-head data consistently shows that GLP-1 receptor agonists bring HbA1c down a bit more than SGLT2 inhibitors. A systematic review and network meta-analysis found that GLP-1 receptor agonists were superior to SGLT2 inhibitors in HbA1c reduction, with an additional drop of about 0.4 percentage points.⁴ Another comparative study confirmed that while both treatments produced meaningful HbA1c reductions, GLP-1 agonists had a slight edge.⁵

That said, the difference is modest. For many people, the gap between the two classes matters less than other factors like side effects, cost, or which organ-protection benefits are more relevant. An SGLT2 inhibitor that you tolerate well and take consistently is going to serve you better than a GLP-1 drug that makes you too nauseated to eat.

Weight Loss

This is where the two classes diverge more sharply. SGLT2 inhibitors produce modest weight loss, generally in the range of 1.5 to 2 kilograms more than placebo, sustained for up to four years. That weight loss comes from the calories lost through urinary glucose excretion, along with some reduction in body fat inflammation.⁶

GLP-1 receptor agonists produce substantially more weight loss because they suppress appetite directly through brain signaling and slow gastric emptying. In people with type 2 diabetes, GLP-1 drugs typically lead to a five to ten percent reduction in body weight. Newer agents push this even further: tirzepatide, the dual GIP/GLP-1 drug, has shown weight reductions of 15 to 20 percent in clinical trials.⁶ If weight loss is a primary treatment goal, GLP-1 drugs have a clear advantage over SGLT2 inhibitors.

Heart Protection

Both classes reduce cardiovascular risk, but they do it in different ways and protect against somewhat different events. SGLT2 inhibitors stand out for reducing hospitalization for heart failure, while GLP-1 receptor agonists are more effective at reducing atherosclerotic cardiovascular events, particularly stroke.⁷ Both classes reduce cardiovascular mortality and all-cause mortality.

The SGLT2 inhibitor benefit in heart failure likely comes from their effect on fluid balance. By promoting sodium and glucose excretion, these drugs cause a mild reduction in plasma volume, which takes pressure off the heart. They also lower blood pressure through this mechanism and potentially through reduced nervous system activity.⁸ This is why SGLT2 inhibitors have been approved for heart failure treatment even in people who do not have diabetes. GLP-1 drugs, meanwhile, appear to reduce cardiovascular events through their effects on weight, blood sugar, inflammation, and possibly direct effects on blood vessel walls.

SGLT2 inhibitors were recognized as a strong second-line therapy after metformin for people with established cardiovascular disease, heart failure, or chronic kidney disease starting in 2018.⁹ So when a doctor prescribes Jardiance to someone who already has heart failure, that prescription is based on a robust evidence base specific to SGLT2 inhibitors, not anything borrowed from GLP-1 data.

Kidney Protection

Both drug classes offer kidney benefits, but the evidence is stronger and more direct for SGLT2 inhibitors when it comes to slowing the decline of kidney function. SGLT2 inhibitors reduce a process called glomerular hyperfiltration, essentially easing the workload on the kidneys’ filtering units. GLP-1 receptor agonists are particularly good at reducing albuminuria, the leaking of protein into urine that signals early kidney damage.¹⁰

A real-world comparison of matched patient groups found that those taking SGLT2 inhibitors had lower rates of worsening kidney disease and better blood pressure changes compared to those on GLP-1 receptor agonists, even though the GLP-1 group had a larger drop in HbA1c.¹¹ Indirect comparisons suggest SGLT2 inhibitors offer greater protection against kidney function decline, though direct head-to-head trials comparing the two classes specifically for kidney endpoints are still lacking.¹⁰

Side Effects

The side-effect profiles are quite different, which often matters as much as efficacy when choosing between the two.

SGLT2 inhibitors push glucose into the urine, which creates a sugar-rich environment that fungi love. Genital yeast infections are the most common side effect, particularly in women. There is also a risk, though uncommon, of diabetic ketoacidosis, a serious condition involving dangerous acid buildup in the blood. The FDA has flagged ketoacidosis cases occurring after SGLT2 inhibitor use.¹² Urinary tract infections and increased urination are also more common because of the mechanism. Some people experience low blood pressure or dizziness from the mild diuretic effect.

GLP-1 receptor agonists have a gastrointestinal side-effect profile that is nearly the opposite. Nausea is the most reported issue, followed by vomiting, diarrhea, and constipation.¹³ A large systematic review found that all evaluated GLP-1 drugs led to a significant increase in nausea risk, though the severity varied by specific drug.¹⁴ These gut symptoms usually improve over time as the dose is gradually increased, which is why GLP-1 prescriptions typically start at a low dose and escalate over weeks or months.

In short: SGLT2 inhibitors tend to cause problems “below the belt” (genital infections, urinary symptoms), while GLP-1 drugs tend to cause problems in the gut (nausea, vomiting). Neither class commonly causes hypoglycemia on its own, which is a meaningful safety advantage over older diabetes drugs like sulfonylureas or insulin.

Pills Versus Injections

Jardiance and other SGLT2 inhibitors are taken as daily oral tablets. Most GLP-1 receptor agonists are weekly injections, with a few exceptions like oral semaglutide (Rybelsus). This practical difference matters a lot to patients. Some people strongly prefer a daily pill; others find a once-weekly injection easier to remember than a daily tablet.

A retrospective study comparing adherence between weekly injectable semaglutide and daily oral empagliflozin (Jardiance) found no significant difference in one-year adherence rates, with roughly similar proportions of patients sticking with each medication. However, persistence was low in both groups: only about 40 to 45 percent of patients were still consistently taking either drug after a year.¹⁵ Those numbers reflect a reality across chronic disease management: people struggle to stay on medications long-term regardless of how convenient the dosing is.

Cost Differences

Both drug classes are expensive, but GLP-1 receptor agonists consistently cost more. A real-world claims analysis found that GLP-1 users had average per-person per-month costs roughly $179 higher than SGLT2 inhibitor users, with the pharmacy cost difference accounting for about $108 of that gap.¹⁶ Out-of-pocket costs also differ: one study found that patients on a GLP-1 drug alone paid roughly double the out-of-pocket costs compared with those on an SGLT2 inhibitor alone.¹⁷

A cost-effectiveness analysis found that as first-line agents (replacing metformin), neither class is currently cost-effective at prevailing U.S. prices. The study estimated that SGLT2 inhibitor prices would need to fall by at least 70 percent, and GLP-1 drugs by a similar margin, before either could be considered cost-effective as initial therapy by standard thresholds.¹⁸ That analysis was done before some price changes and the arrival of generics in some markets, but the overall picture remains: these are premium medications, and insurance coverage varies widely.

Using Both Together

Because SGLT2 inhibitors and GLP-1 receptor agonists work through completely different mechanisms, there is growing interest and evidence for combining them. The logic is straightforward: one drug works at the kidney, the other works at the pancreas, gut, and brain. They do not interfere with each other and may add up to greater benefits than either alone.

Research supports this idea. Combination therapy has been found to produce additive effects on blood sugar control without increasing the risk of dangerous low blood sugar, along with synergistic effects on weight loss and blood pressure.¹⁹ A meta-analysis of real-world cohort studies found that the combination was associated with roughly half the risk of major cardiovascular events, about half the risk of kidney disease progression, and about half the risk of death from any cause compared to using either drug class alone.²⁰

A modeling study estimated the lifetime benefits for a 50-year-old patient starting combination therapy (an SGLT2 inhibitor, a GLP-1 drug, and a nonsteroidal mineralocorticoid receptor antagonist) compared to conventional care. The projected gains were substantial: an estimated 3.2 additional years free of major cardiovascular events, 5.5 additional years free of kidney disease progression, and about 2.4 extra years of life overall.²¹ These are modeled projections rather than results from a completed trial following patients for decades, but they reflect the direction the evidence is pointing.

What Happens When You Stop a GLP-1 Drug

One practical difference worth understanding is what happens after discontinuation. SGLT2 inhibitors work on a straightforward mechanism: as long as you take the pill, your kidneys excrete extra glucose. Stop the pill, and kidney function goes back to normal glucose reabsorption. Blood sugar rises back up, but without the dramatic rebound effects seen with GLP-1 drugs.

Stopping a GLP-1 receptor agonist, on the other hand, triggers a more conspicuous rebound. A systematic review found that virtually all studies observed weight regain after stopping GLP-1 treatment, with the amount regained at about 12 weeks ranging from roughly 10 to 80 percent of the weight initially lost.²² HbA1c also crept back up, with about half the initial improvement lost within 8 to 12 weeks, though it rarely returned all the way to pre-treatment levels even a year later.²²

A separate meta-analysis quantified this more precisely. In people with obesity who stopped a GLP-1 drug, the average weight regain was about 5.6 kilograms, along with increases in waist circumference, blood pressure, and fasting blood sugar. The rebound was more pronounced after longer treatment and was greater with semaglutide than with liraglutide.²³ This does not mean the drugs are a trap, but it does mean that GLP-1 therapy is typically intended as long-term treatment rather than a course you complete and stop. If you are considering one of these medications for weight management, planning for sustained use is an important part of the conversation with your doctor.

When Doctors Choose One Over the Other

The decision between an SGLT2 inhibitor and a GLP-1 receptor agonist often comes down to which problems are most pressing for a given patient. If heart failure is the primary concern, SGLT2 inhibitors have the strongest evidence. If the patient needs significant weight loss or has a history of stroke or atherosclerotic cardiovascular disease, GLP-1 drugs may be the better fit. For kidney protection in chronic kidney disease, SGLT2 inhibitors currently have more direct trial evidence, though GLP-1 drugs also help. For pure blood sugar control, both work well, with GLP-1 drugs having a small advantage.

Tolerability plays a role too. Someone prone to urinary tract infections or with a history of ketoacidosis risk factors may want to avoid SGLT2 inhibitors. Someone with severe gastroparesis or a strong aversion to needles may prefer the oral SGLT2 route. Cost and insurance coverage frequently end up being the deciding factor in practice, since both classes remain expensive and coverage can differ dramatically between plans. And increasingly, the answer is not “one or the other” but both, used together for patients with multiple cardiometabolic risk factors who can access and afford the combination.