Jardiance (empagliflozin) and metformin are prescribed together because they lower blood sugar through completely different mechanisms, giving you better glucose control than either drug alone. This combination also offers benefits beyond blood sugar, including weight loss, lower blood pressure, and protection for your heart and kidneys.
They Work on Different Parts of Your Body
The core reason these two medications pair so well is that they attack high blood sugar from two separate angles. Metformin works primarily in the liver, where it reduces the amount of glucose your liver produces and releases into your bloodstream. Jardiance works in the kidneys, where it blocks a protein that normally reabsorbs sugar from your urine back into your blood. With that protein blocked, excess glucose leaves your body when you urinate instead of recirculating.
Because these pathways don’t overlap, the drugs complement each other without doubling up on the same biological process. This also means the combination carries a low risk of hypoglycemia (dangerously low blood sugar), since neither drug forces the pancreas to produce more insulin the way some older diabetes medications do.
Better Blood Sugar Control Together
Metformin is typically the first medication prescribed for type 2 diabetes. It works well for many people, but over time blood sugar levels can creep upward as the disease progresses. When metformin alone no longer keeps your A1C at target, adding a second drug with a different mechanism is the standard next step. Jardiance is one of the most commonly chosen additions.
In clinical trials of people already taking metformin, adding Jardiance brought A1C levels down further, with greater reductions seen in those who started with higher A1C values. The combination is effective enough that a fixed-dose pill called Synjardy XR combines both drugs in a single tablet, available in several strengths ranging from 5 mg of empagliflozin with 1,000 mg of metformin up to 25 mg of empagliflozin with 1,000 mg of metformin.
Weight Loss and Blood Pressure Benefits
One of the practical advantages of this pairing is that both drugs are weight-neutral or weight-favorable. Metformin tends to cause modest weight loss or at least doesn’t cause gain. Jardiance goes further: because you’re literally excreting glucose (and its calories) in your urine, weight loss is a consistent side effect.
In studies of people taking metformin who then added Jardiance, the weight loss at 24 weeks ranged from about 1.4 kg to 2.9 kg (roughly 3 to 6.5 pounds) compared to those who stayed on metformin with a placebo, depending on the dose and starting weight. By 76 weeks, some groups lost over 4 kg (about 9 pounds) more than the placebo group. People who weighed more at the start tended to lose more.
Jardiance also lowers systolic blood pressure, which showed up consistently across clinical trials regardless of participants’ starting blood pressure. For someone with type 2 diabetes who is also managing weight and blood pressure, this combination addresses multiple risk factors at once.
Heart and Kidney Protection
This is where the combination becomes especially compelling. Type 2 diabetes significantly raises the risk of heart failure, heart attack, and kidney disease. Jardiance has strong evidence for reducing cardiovascular events and slowing kidney damage, effects that appear to go beyond just lowering blood sugar.
Metformin also offers some kidney-protective effects by reducing cell damage and inflammation in kidney tissue. Research comparing the drugs individually and together found that the combination produced additive protective effects on the kidneys. Animals treated with both drugs showed lower markers of inflammation and less kidney tissue damage than those treated with either drug alone. Blood markers of kidney function, including urea and creatinine, improved more with the combination.
Both medications also reduce inflammation, which is a key driver of the organ damage that makes diabetes so dangerous over time. Jardiance in particular has notable anti-inflammatory and antioxidant properties beyond its glucose-lowering effect.
What Side Effects to Expect
Each drug brings its own set of potential side effects, and taking them together means you could experience effects from either one.
Metformin’s most common issues are gastrointestinal: nausea, diarrhea, stomach discomfort, and decreased appetite, especially when you first start taking it. These usually improve over a few weeks. A rare but serious concern with metformin is lactic acidosis, a buildup of lactic acid in the blood. Symptoms include unusual tiredness, muscle cramping, fast or shallow breathing, and stomach pain that doesn’t resolve.
Jardiance’s side effects reflect its mechanism. Because it increases sugar in your urine, it creates an environment where yeast and bacteria thrive. Urinary tract infections are more common, and genital yeast infections affect both women and men. Women may notice vaginal itching or discharge; men may experience redness, itching, or swelling around the penis. These infections are usually mild and treatable, but persistent or severe urinary symptoms warrant prompt attention.
Importantly, the combination does not significantly increase the risk of low blood sugar compared to metformin alone, which is a major advantage over some other add-on medications.
Who Can Safely Take Both
Kidney function is the main factor that determines whether this combination is appropriate. Jardiance relies on the kidneys to work, so it is not recommended for blood sugar control in people whose estimated kidney filtration rate (eGFR) falls below 30. People with eGFR below 60, older adults, and those taking water pills may face a higher risk of dehydration or low blood pressure on Jardiance, so kidney function and fluid status are typically checked before starting.
Metformin has its own kidney thresholds. It is generally not started in people with severely reduced kidney function, because impaired kidneys increase the risk of lactic acidosis. Your kidney function will be tested before you begin either drug and periodically while you take them.
For most people with type 2 diabetes and at least moderate kidney function, the combination of Jardiance and metformin offers a well-matched pair: two drugs that lower blood sugar through independent pathways, don’t cause hypoglycemia, promote modest weight loss, lower blood pressure, and protect the organs most vulnerable to diabetes-related damage.