Type 2 diabetes often progresses over time, and many people eventually need more than one medication to keep their blood sugar in range. According to the American Diabetes Association (ADA), if someone’s A1C is 1.5% to 2% above their goal at diagnosis, starting with two medications may be a better option.
Jardiance (empagliflozin) and metformin are two widely prescribed drugs for lowering blood sugar and reducing the risk of diabetic complications. When used together, they target blood sugar in different ways.
In practice, Jardiance is taken once daily in the morning, with or without food. Immediate-release metformin is usually taken twice daily with meals, while extended-release metformin is taken once daily with the evening meal. There is no need to separate the two medications, and they can be taken together if timing overlaps.
This article explains how each drug works, when they are typically taken, who may benefit from combination therapy, and practical tips for fitting them into your daily routine.
Understanding Jardiance (empagliflozin)
Here’s what to know about Jardiance.
How does Jardiance work?
Jardiance is a sodium-glucose cotransporter 2 (SGLT2) inhibitor. It blocks glucose reabsorption in the kidneys, causing the body to pass excess sugar in the urine. Because it works in the kidneys, its blood-sugar-lowering effect does not depend on insulin.
Clinical studies show that empagliflozin reduces urinary glucose reuptake by about 64 grams/day at 10 mg and 78 grams/day at 25 mg, which lowers blood sugar and encourages modest weight loss. Its diuretic effect also reduces blood pressure without increasing heart rate.
Beyond glucose control, Jardiance offers cardiovascular and kidney benefits. A 2025 systematic review of randomized controlled trials found that empagliflozin reduces major adverse cardiovascular events and provides a 14-38% reduction in cardiovascular mortality with 23-35% fewer hospitalizations for heart failure.
These benefits have made SGLT2 inhibitors preferred second-line agents for people with heart failure or chronic kidney disease on top of metformin.
How do you take Jardiance for diabetes?
For adults with type 2 diabetes or heart-failure indications, the typical starting dose is 10 mg once a day. The dose may be increased to 25 mg once daily if needed.
The drug can be taken with or without food, and the official medication guide recommends taking it once in the morning. Clinical guidelines advise sticking to the same time each day to maintain steady drug levels.
When is the best time of day to take Jardiance?
Because Jardiance promotes urination, many people take it in the morning to reduce nighttime trips to the bathroom.
A pharmacokinetic study in 2021 compared 10 mg empagliflozin taken in the morning versus at night and found that both schedules appear equally effective. The drug was absorbed properly either way, and the glucose-lowering effect did not meaningfully change based on timing.
The most important factor is consistency. Take it at the same time each day unless your healthcare provider advises otherwise.
Is Jardiance safe?
Yes, but like all medicines, Jardiance has benefits and risks. The StatPearls medical review lists several noteworthy adverse effects:
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- Low blood pressure & dehydration – Empagliflozin causes diuresis and can lead to volume depletion and symptomatic hypotension, especially in older adults or those taking diuretics, ACE inhibitors, or ARBs.
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- Genital and urinary infections – Increased glucose in the urine raises the risk of genital yeast infections and urinary tract infections. Signs include itching, burning, or unusual discharge.
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- Ketoacidosis – SGLT2 inhibitors can precipitate ketoacidosis, sometimes with normal blood sugar levels. Risk factors include dehydration, pancreatic disorders, and excessive alcohol use.
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- Renal issues – Empagliflozin is not recommended when the estimated glomerular filtration rate (eGFR) is less than 30 mL/min/1.73 m². The medicine can increase creatinine and lower eGFR, so kidney function must be checked regularly.
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- Hypoglycemia – On its own, Jardiance rarely causes hypoglycemia, but the risk increases when combined with insulin or sulfonylureas.
Other rare but serious concerns include Fournier gangrene and an increased risk of foot amputations, reported with some SGLT2 inhibitors. Seek medical attention if you notice unusual pain, swelling, or infection.
Understanding Metformin
For decades, metformin has remained the first-line medication for type 2 diabetes.
How does metformin work?
Metformin is a biguanide that lowers blood sugar in two main ways:
1. It tells your liver to make less sugar. Your liver naturally releases glucose into your bloodstream. In people with type 2 diabetes, the liver often releases too much. Metformin slows that down.
2. It helps your body use insulin better. Insulin helps move sugar from your blood into your cells for energy. Metformin makes your muscles and other tissues more responsive to insulin, so they absorb sugar more efficiently.
It is generally weight-neutral or can cause modest weight loss and is inexpensive.
Metformin’s benefits go beyond blood sugar as well. The landmark UK Prospective Diabetes Study (UKPDS) showed that metformin use in overweight adults with type 2 diabetes reduced diabetes-related endpoints, myocardial infarction, and all-cause mortality compared with conventional therapy.
Subsequent observational studies and meta-analyses have confirmed associations between metformin use and lower all-cause and cardiovascular mortality and fewer heart-failure hospitalizations.
How many mg of metformin can you take a day?
Metformin comes in immediate-release and extended-release forms. According to the Mayo Clinic:
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- Immediate-release tablets – Adults often start at 500 mg twice daily (morning and evening) or 850 mg once daily. The dose may increase gradually to a maximum of 2,550 mg/day, divided into two or three doses. These tablets should be taken with meals to reduce stomach upset.
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- Extended-release (XR) tablets – Usually taken once daily with the evening meal, starting at 500-1000 mg and increasing to 2,000-2,500 mg/day. Metformin XR tablets are swallowed whole and should not be crushed or chewed.
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- Liquid – For those who have difficulty swallowing pills, a liquid form is available and is taken with meals. Doses start at 5 mL once a day, taken with the evening meal, and increase to 20 mL per day.
When is the best time to take metformin?
Traditional advice is to take metformin with food to lessen stomach and bowel side effects. But emerging research suggests that timing may influence its glucose-lowering effect.
A pharmacokinetic modeling study from 2023 found that metformin levels in the blood are 42% higher in the morning than in the evening. It also suggested that a dose taken at 23:30 or 11:30 PM could result in higher levels by the next morning because the body clears the drug more slowly overnight.
Another study published in Diabetologia suggests that taking metformin 30 to 60 minutes before a meal may improve post-meal blood sugar control compared to taking it at the start of the meal.
However, these findings are not yet incorporated into clinical practice. There is no consensus on changing the long-standing recommendation of taking metformin with meals. If you tolerate the medication well, your healthcare provider may consider adjusting the timing to improve blood-sugar control, but such changes should be individualized.
What are the side effects and risks of metformin?
Most people tolerate metformin, but some experience side effects. Nausea, diarrhea, gas, bloating, and stomach pain are common when starting therapy. Other effects include weight loss, headaches, and a metallic taste. Starting with a low dose and taking the medicine with food helps minimize these symptoms.
Severe side effects are rare but important to understand:
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- Vitamin B12 deficiency – Long-term metformin use can interfere with vitamin B12 absorption. Vitamin B12 deficiency can cause nerve damage, anemia, memory problems, and other blood issues. It can be hard to diagnose and often requires several tests. Experts suggest checking B12 levels if you have been on metformin for four years or more.
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- Lactic acidosis – This potentially life-threatening condition occurs when lactate builds up in the blood. It is extremely rare and usually linked to kidney impairment or acute illness. Analysis of FDA adverse-event reports found that diabetes, heart disease, and hypertension are associated with higher odds of metformin-associated lactic acidosis.
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- Hypoglycemia – Metformin alone rarely causes low blood sugar, but the risk increases when it is used with insulin or sulfonylureas.
Because metformin is excreted by the kidneys, guidelines recommend that it should not be started if eGFR is below 45 mL/min/1.73 m² and is contraindicated when eGFR is under 30 mL/min/1.73 m². People with liver disease, heart failure, or heavy alcohol use also need careful monitoring.
Can you take Jardiance and metformin together?
Yes. Using Jardiance and metformin together can provide greater blood sugar control and complementary cardiovascular and kidney protection.
In a phase 3 trial involving adults with type 2 diabetes whose glucose was uncontrolled on metformin and sitagliptin, adding empagliflozin 10 mg or 25 mg lowered HbA1c by 0.7% and 0.8%, respectively, compared with placebo after 24 weeks. More participants also reached HbA1c targets (< 7% or < 6.5%), fasting glucose improved, and benefits continued during a 28-week extension.
The combination also reduced body weight and albuminuria, with a safety profile similar to placebo. These results show that adding empagliflozin to metformin improves glycemic control without major safety concerns.
When is the best time to take Jardiance and metformin?
When using separate tablets, take Jardiance in the morning, with or without food. With metformin, the timing depends on the formulation:
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- Immediate-release metformin – Commonly taken twice daily with breakfast and dinner.
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- Extended-release metformin – Taken once daily with the evening meal.
There is no strict requirement to separate Jardiance and metformin doses. Taking them together at breakfast is acceptable if you are on twice-daily metformin, then take the second metformin dose with dinner.
For once-daily metformin, you might take Jardiance in the morning, then take the metformin dose in the evening with your dinner.
Dosing schedule for combination products (Synjardy)
There is already a single-pill combination of empagliflozin (Jardiance) and metformin. The brand name is Synjardy. It comes in immediate-release tablets and extended-release versions.
Standard Synjardy tablets are taken orally twice daily with meals, while Synjardy XR (extended release) is taken once daily with a morning meal. Tablets should be swallowed whole. Do not split or crush.
Available Synjardy Dosages
Synjardy Tablets (Immediate-Release):
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- 5 mg empagliflozin / 500 mg metformin
- 5 mg empagliflozin / 1,000 mg metformin
- 12.5 mg empagliflozin / 500 mg metformin
- 12.5 mg empagliflozin / 1,000 mg metformin
Synjardy XR Tablets (Extended-Release):
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- 5 mg empagliflozin / 1,000 mg metformin ER
- 10 mg empagliflozin / 1,000 mg metformin ER
- 12.5 mg empagliflozin / 1,000 mg metformin ER
- 25 mg empagliflozin / 1,000 mg metformin ER
Other factors to consider when taking Jardiance and metformin
Beyond timing, a few practical factors can affect how you take these medications.
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- Sleep patterns – Jardiance increases urination, so taking it too late in the day may cause nighttime bathroom trips and disrupt sleep. For most people, morning dosing works best. If you work night shifts or sleep during the day, take Jardiance when you wake up for your main active period.
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- Meal schedules – Metformin is taken with food to reduce stomach upset. If you regularly skip breakfast, do not force a morning dose just to follow a standard schedule. Instead, align your dose with your eating schedule for better tolerance and consistency.
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- Kidney and liver function – Impaired kidney function necessitates dose adjustments or avoidance for both drugs. Regular monitoring helps determine the safest schedule.
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- Other medications – Loop diuretics, ACE inhibitors, and ARBs can amplify Jardiance’s diuretic effects, raising the risk of hypotension. Furosemide and certain blood-pressure drugs also increase the risk of metformin-associated lactic acidosis. Your doctor may suggest taking such medicines at different times or adjusting doses.
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- Pregnancy and breastfeeding – Empagliflozin is not recommended during the second and third trimesters of pregnancy. Metformin is sometimes used in pregnancy, but timing and dosing should be managed by an obstetrician.
Bottom line
Taking Jardiance and metformin together delivers improved blood-sugar control and cardiovascular protection. Evidence shows that taking Jardiance once daily in the morning maintains consistent levels and minimizes nighttime bathroom trips. Metformin should generally be taken with meals to reduce gastrointestinal side effects. Combination tablets like Synjardy simplify the regimen by pairing both drugs in one pill, but they should still be taken with meals.
The best schedule is the one that you can follow consistently with minimal side effects. Ask your doctor to personalize your medication timing around your routine and health status.
Frequently Asked Questions
Related Articles
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