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Empagliflozin and Metformin: A Promising Combination for Managing Type 2 Diabetes

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10 min read


Empagliflozin and Metformin combination treats type 2 diabetes by lowering the amount of glucose the liver produces.

Written by

Dr. Kinjal Shah

Medically reviewed by

Dr. Raveendran S R

Published At October 27, 2023
Reviewed AtOctober 27, 2023


Two active components comprise the combination drug Empagliflozin and Metformin: Empagliflozin and Metformin. Metformin is a biguanide, whereas Empagliflozin is a sodium-glucose cotransporter-2 (SGLT2) inhibitor. By boosting the quantity of glucose discharged in the urine and lowering the amount of glucose generated by the liver, they reduce blood sugar levels in people with type 2 diabetes. This drug is frequently used with diet and exercise to treat diabetes and is commonly taken orally once or twice a day. As part of an all-encompassing treatment strategy, it may also be used with additional diabetic drugs.

Drug Group

The combination of Empagliflozin and Metformin is classified as an anti-diabetic drug. It combines two different pharmacological classes, an SGLT2 inhibitor (Empagliflozin) and a biguanide (Metformin), to give people with type 2 diabetes mellitus (T2DM) thorough glycemic control.

Available Doses and Dosage Forms:

The combination of Empagliflozin and Metformin is offered in a range of dosages and dosage forms to meet the needs of different patients and achieve varied therapeutic objectives. Typical dosages and formats include:

  • Tablets of five mg (milligrams) or 500 mg of Empagliflozin or Metformin

  • Tablets of five mg/1000 mg Empagliflozin/Metformin.

  • Tablets of 10 mg/500 mg Empagliflozin/Metformin.

  • Tablets of 10 mg/1000 mg Empagliflozin/Metformin.

For Patients:

What Is Type 2 Diabetes?

A chronic metabolic condition called type 2 diabetes mellitus (T2DM) is characterized by high blood glucose levels brought on by insulin resistance and decreased insulin production. By making it easier for glucose to enter cells, the hormone insulin aids in controlling blood sugar (glucose) levels. In T2DM, the body's cells develop an immunity to the actions of insulin, which results in decreased glucose absorption and increased blood glucose levels. The pancreas may eventually find it difficult to generate enough insulin to overcome this resistance, raising blood glucose levels.

How Does Empagliflozin and Metformin Work?

  • Empagliflozin: It functions by inhibiting the kidney's sodium-glucose co-transporter 2 (SGLT2) protein. Reabsorbing glucose into the circulation is carried out by this protein. Empagliflozin reduces glucose reabsorption by inhibiting SGLT2, causing more glucose to be discharged in the urine. This reduces blood glucose levels without insulin and aids in weight reduction since it burns calories through glucose excretion.

  • Metformin: A biguanide, Metformin primarily affects the liver to decrease glucose synthesis. Additionally, it improves peripheral tissues' sensitivity to insulin, such as muscle cells, enabling them to react to insulin and absorb glucose more effectively. Metformin also reduces the amount of glucose absorbed by the digestive system.

Empagliflozin and Metformin work together to increase insulin sensitivity, accomplish more thorough glycemic control, and may even have additional advantages like weight loss because of their unique modes of action.

What Is the Dosage of Empagliflozin and Metformin?

Depending on the precise combination pill provided and the patient's unique characteristics, the dosage of Empagliflozin/Metformin may change. Here are a few typical dosages:

  • Empagliflozin and Metformin - five mg/500 mg Tablets:

    • Empagliflozin: Five mg.
    • Metformin: 500 mg.
  • Empagliflozin and Metformin - five mg/1000 mg Tablets:

    • Empagliflozin: Five mg.
    • Metformin: 1000 mg.
  • Empagliflozin and Metformin - 10 mg/500 mg Tablets:

    • Empagliflozin: 10 mg.
    • Metformin: 500 mg.
  • Empagliflozin and Metformin - 10 mg/1000 mg Tablets:

    • Empagliflozin: 10 mg.
    • Metformin: 1000 mg.

Dosage instructions are typically provided by a healthcare provider based on factors such as the patient's current blood glucose levels, renal function, response to treatment, and potential side effects.

How Effective Is Empagliflozin and Metformin?

It has been demonstrated that Empagliflozin and Metformin work well together to manage type 2 diabetes. Clinical studies have shown that it can enhance glycemic management, lower blood glucose levels, and offer further advantages, including weight loss, lowered cardiovascular risk, and possibly kidney protection.

The synergistic effects of Metformin and Empagliflozin are likely responsible for the combination's efficacy. Metformin's effects on lowering hepatic glucose synthesis and enhancing insulin sensitivity, coupled with Empagliflozin's capacity to improve urine glucose excretion, lead to more thorough glucose management.

What Are the Things to Inform the Doctor Before Taking the Drug?

Before initiating the use of Empagliflozin and Metformin or any pharmaceutical, it is imperative to provide the healthcare professional with essential information, including:

  • Medical History: The individual should divulge any prevailing medical conditions, such as kidney impairments, liver ailments, cardiac issues, or any prior instances of diabetic ketoacidosis, enabling the physician to tailor the treatment approach accordingly.

  • Current Medications: A comprehensive inventory of ongoing medications, dietary supplements, or herbal products is essential. This disclosure is pivotal in forestalling potential interactions between drugs and ensuring optimal treatment outcomes.

  • Allergies: Communicating hypersensitivities to medications, foods, or substances empowers the medical team to select medications that align with the individual's sensitivities, preventing adverse reactions.

  • Pregnancy or Breastfeeding: If the individual is expecting, planning to conceive, or breastfeeding, a collaborative discussion with the doctor regarding the medication's potential risks and benefits is fundamental for making informed decisions.

  • Renal Function: Given Empagliflozin's renal excretion, a comprehensive evaluation of renal function is imperative. This evaluation allows the medical practitioner to calibrate the treatment regimen appropriately.

  • Cardiovascular History: A comprehensive understanding of one's cardiovascular history, encompassing any cardiovascular disease, heart failure, or related conditions, is pivotal in devising a treatment plan that aligns with the individual's health profile.

  • Upcoming Surgery: Communicating any impending surgical procedures, including dental interventions, is critical. This information enables the healthcare provider to optimize the medication regimen considering the surgical context.

  • Alcohol Consumption: Transparent communication regarding alcohol consumption is integral due to potential interactions between alcohol and certain medications. Providing accurate information empowers the healthcare team to make well-informed decisions.

How Is Empagliflozin and Metformin Administered?

Administering the Empagliflozin and Metformin combination involves a set of essential considerations to guarantee its safety and efficacy:

  • Dosage and Timing: The healthcare provider should determine the specific dosage and timing for the Empagliflozin and Metformin combination, considering the individual's medical history and requirements. Strict adherence to the prescribed dosage instructions is vital.

  • Dosing Frequency: Individuals are advised to take the combination once daily. The healthcare provider will guide on the optimal time for administration, often in conjunction with a meal, to mitigate the potential gastrointestinal effects of Metformin.

  • Renal Function: Given that Empagliflozin is excreted via the kidneys, individuals with impaired renal function may require dosage adjustments to ensure the safe and efficient utilization of the medication.

  • Monitoring: Regular monitoring of blood glucose levels is a crucial indicator of the medication's effectiveness. This data aids healthcare providers in making necessary adjustments to the treatment plan as required.

  • Combination Tablets: Convenience is offered through the combination tablets, which provide both medications in a singular dose. This streamlined approach enhances convenience and adherence to the treatment regimen.

  • Missed Dose: In the event of a missed dose, consulting the healthcare provider is advisable to determine whether the missed dose should be taken or if any modifications to the schedule are necessary.

  • Healthcare Provider Consultation: Regular and transparent communication with the healthcare provider is essential for addressing concerns, managing side effects, and conveying any alterations in health status. The healthcare provider can offer guidance and address queries regarding administering the Empagliflozin and Metformin combination.

What Are the Side Effects of Empagliflozin and Metformin?

The following are possible adverse effects of Empagliflozin and Metformin:

  • Gastrointestinal Distress: Abdominal pain and gastrointestinal symptoms, such as nausea, vomiting, diarrhea, and Metformin-specific symptoms, might occur.

  • Urinary Tract Infections: The mechanism of action of Empagliflozin may make urinary tract infections more likely. Increased frequency, urgency, discomfort, or burning feeling while urinating may be symptoms.

  • Genital Fungal Infections: An additional risk of genital fungal infections, which may result in itching, redness, or pain, is a possible adverse effect of Empagliflozin.

  • Hypoglycemia: Taking anti-diabetic drugs like Metformin and Empagliflozin might cause low blood sugar levels (hypoglycemia). However, this is rare. This risk is critically high if the drug does not match an acceptable nutritional intake.

  • Low Blood Pressure and Dehydration: The diuretic action of Empagliflozin may cause dehydration and a decline in blood pressure. It is essential to drink enough water when using this medicine.

  • Lactic Acidosis: Despite its rarity, Metformin can cause lactic acidosis, a dangerous illness characterized by muscular discomfort, respiratory problems, and a general sensation of weakness. People who have poor liver or renal function are more vulnerable.

Dietary Guidelines:

Diet is crucial for controlling type 2 diabetes and can affect how well Empagliflozin and Metformin work. Here are some food recommendations:

  • Carbohydrate Intake: Watch the consumption of carbohydrates to help control blood sugar levels. Incorporating the medicine into a carbohydrate diet can help prevent hypoglycemia.

  • Water intake: Due to the diuretic properties of Empagliflozin, it is essential to drink plenty of water to avoid dehydration and preserve kidney function.

  • Drinking Alcohol: If one wants to do so, do it sparingly and be mindful of drug interactions. Alcohol may make hypoglycemia more likely.

  • Regular Meals: Controlling portion sizes and meal times can help stabilize blood sugar levels. Create a customized meal plan in cooperation with a licensed dietician.

  • Fruit and Vegetables: Make a diet high in fruits, vegetables, healthy grains, and lean proteins a priority. These decisions may have a favorable effect on controlling blood sugar.

  • Consult a Registered Dietitian: A registered dietitian with knowledge of diabetes management can assist in developing a personalized dietary plan compatible with the medication schedule.

  • Monitor Blood Sugar: Regularly check the blood sugar levels to see how food and medicines affect them.

Missed Dose:

  • Missed Dose of Metformin: If a dose of Metformin is omitted, the individual should take it as soon as possible unless it is near the next scheduled dose. In such cases, skipping the missed dose and returning to the regular dosing routine is advised.

  • Missed Dose of Empagliflozin: In situations where a dose of Empagliflozin is overlooked, it should be taken as soon as remembered on the same day. If an entire day has transpired, forgoing the missed dose and resuming the customary dosing regimen the following day is recommended.

Refraining from ingesting a double dose is essential to compensate for a missed one, as this could heighten the risk of adverse reactions.


When a potential Empagliflozin and Metformin combination overdose is suspected, promptly seeking medical attention or contacting a poison control center is imperative. Overdose symptoms may encompass severe hypoglycemia (markedly low blood sugar), lactic acidosis (in the case of Metformin), and other unfavorable effects. Swift medical intervention is critical to managing any potential complications.


Prudent storage of the Empagliflozin and Metformin combination is pivotal in upholding its potency and safety:

  • Temperature: The medication should be stored at room temperature, removing excessive heat, moisture, and direct sunlight.

  • Original Packaging: Maintaining the tablets within their original container is advisable, ensuring the packaging is securely sealed to avert moisture infiltration.

  • Childproof Container: If supplied in a childproof container, ensuring proper resealing after each use is essential to forestall unintended consumption by children.

  • Out of Reach: Safeguarding the medication beyond the reach of children and pets is essential to prevent inadvertent ingestion.

  • Disposal: Expired or unused medication should be disposed of by local regulations. Flushing medications down the toilet or pouring them into drains should only be undertaken if explicitly instructed.

  • Preservation of Information: Keeping the medication's packaging and any pertinent information for future reference is prudent.

For Doctors:


The combination of Empagliflozin and Metformin is prescribed to address the management of type 2 diabetes mellitus. This co-administration serves the purpose of regulating blood glucose levels in individuals diagnosed with this specific medical condition.


The appropriate dosage of the Empagliflozin and Metformin combination hinges on individual patient variables. Various dosage alternatives include:

  1. Empagliflozin and Metformin: Five mg/500 mg Tablets.

  2. Empagliflozin and Metformin: Five mg/1000 mg Tablets.

  3. Empagliflozin and Metformin: 10 mg/500 mg Tablets.

  4. Empagliflozin and Metformin: 10 mg/1000 mg Tablets.

Dosing Considerations:

Several crucial considerations must be accounted for in determining the appropriate dosing strategy for the Empagliflozin and Metformin combination:

  • Personalization: Tailoring the dosage to the individual depends on factors like the patient's existing glycemic control, response to treatment, renal function, and other pertinent medical aspects.

  • Renal Function: Given that Empagliflozin and Metformin are eliminated through renal processes, evaluating renal function is pivotal. Dosage adjustments might be necessary for individuals with compromised kidney function.

  • Titration: Commencing with a lower dosage and incrementally adjusting it upward might be contemplated by the healthcare provider to attain optimal glycemic control while minimizing potential adverse effects.

  • Adherence: The convenience of combination tablets can foster adherence to the recommended treatment regimen.

  • Monitoring: Regular monitoring of blood glucose levels is essential for gauging the effectiveness of the medication and making appropriate dosage modifications when necessary.

  • Concurrent Medications: The use of any other medications must be factored in to forestall possible interactions that could influence the efficacy or safety of the Empagliflozin and Metformin combination.

What Are the Pharmacological Aspects of Empagliflozin and Metformin?


  • Empagliflozin: It affects the renal tubules' sodium-glucose co-transporter 2 (SGLT2). Empagliflozin increases glucose excretion through urine by decreasing the reabsorption of glucose in the kidneys. Independent of insulin action, this activity lowers blood glucose levels. Additionally, due to the caloric loss brought on by glucose excretion, Empagliflozin may cause a little weight reduction.

  • Metformin: It lessens the liver's ability to produce glucose, preventing an excessive flow of glucose into the circulation. Additionally, it improves peripheral tissues' sensitivity to insulin, such as muscles, enabling cells to absorb glucose and respond to insulin more efficiently. The intestinal absorption of glucose may be reduced with Metformin.


Empagliflozin and Metformin work together to improve glycemic control by making use of their complementary modes of action:

  • Dual Glucose Regulation: Empagliflozin inhibits SGLT2, which lowers renal reabsorption of glucose and increases urine excretion of glucose. This effect is complemented by Metformin's impact on hepatic glucose synthesis and peripheral insulin sensitivity.

  • Improved Insulin Sensitivity: Metformin increases the sensitivity of peripheral tissues to insulin, enabling cells to absorb glucose from the circulation more effectively.

  • Caloric Loss: Empagliflozin's method for excreting glucose causes a loss of calories, which might help with weight loss.


  • After being taken by mouth, Empagliflozin is absorbed through the digestive system. It is mostly broken down in the liver and excreted through the kidneys and feces. Its elimination half-life is 12.4 hours or such.

  • Metformin mostly affects the liver and is absorbed in the upper small intestine. Through the kidneys, it is eliminated intact since it is not metabolized. Metformin has an elimination half-life of about 6.2 hours.


Clinical Toxicity

Key clinical toxicity considerations encompass:

  1. Hypoglycemia.

  2. Genital and urinary tract infections.

  3. Dehydration and hypotension.

  4. Lactic acidosis.

Clinical Studies:

Clinical trials offer crucial insights into the safety and effectiveness of the combination in type 2 diabetes management:

  • Efficacy Assessment: Trials gauge the combination's ability to lower blood glucose, often measured through reductions in HbA1c levels.

  • Adverse Event Monitoring: Participants are closely observed for potential side effects like hypoglycemia, infections, and gastrointestinal discomfort.

  • Cardiovascular Impact: Cardiovascular outcomes are scrutinized to understand the impact on heart health.

  • Renal Function Evaluation: Given Empagliflozin's influence on the kidneys, trials investigate its effects on renal function.

  • Weight Variation: Studies analyze any changes in weight due to Empagliflozin's mechanism of caloric loss.

  • Inclusive Demographics: Trials encompass diverse groups, including the elderly and those with renal conditions, to ensure efficacy and safety across patient profiles.

  • Long-Term Observations: Extended trials provide insights into the combination's effectiveness over prolonged periods.

  • Comparative Insights: Some trials compare the combination to alternative treatments to ascertain relative advantages.

What Are the Contraindications?

Contraindications delineate situations where medication use is discouraged due to potential risks. For the Empagliflozin and Metformin combination, contraindications encompass:

  • Severe Renal Impairment: Usage is contraindicated in individuals with markedly reduced kidney function, indicated by an estimated glomerular filtration rate (eGFR) below a specified threshold.

  • Metabolic Acidosis History: Individuals with a history of metabolic acidosis, including diabetic ketoacidosis, should avoid the combination.

  • Hypersensitivity: Those with known hypersensitivity to Empagliflozin, Metformin, or any combination components should refrain from its use.

Warnings and Precautions:

Before prescribing Empagliflozin and Metformin, healthcare providers should factor in the following precautions:

  • Dehydration and Low Blood Pressure: Empagliflozin's diuretic effect heightens the risk of dehydration and low blood pressure, necessitating adequate fluid intake.

  • Ketoacidosis: Monitoring for ketoacidosis signs is vital, particularly during fasting, caloric restriction, or alcohol consumption.

  • Renal Function Monitoring: Regular renal function checks, including eGFR, are crucial, particularly in patients with existing kidney issues.

  • Urinary Tract Infection Susceptibility: Patients should be educated about heightened urinary tract infection risk and the importance of timely treatment.

What Are the Drug Interactions of Empagliflozin and Metformin?

The Empagliflozin and Metformin combination can interact with various medications, including:

  • Diuretics: Co-use with diuretics may elevate dehydration and hypotension risks.

  • Insulin and Insulin Secretagogues: The combination can amplify insulin and insulin secretagogues' hypoglycemic effects, necessitating vigilant monitoring.

  • Renal Function-Modifying Drugs: Medications influencing renal function may interact with Empagliflozin and Metformin, affecting their efficacy and safety.

  • Cationic Medications: Certain antiretrovirals and contrast agents, acting as cationic drugs, can reduce Metformin absorption and impact its efficacy.

Specific Considerations:

  • Renal Impairment: Tailored dosing or alternate treatments should be contemplated for patients with varied degrees of renal impairment.

  • Hypoglycemia Risk: Individuals using insulin or insulin secretagogues alongside the combination face heightened risk.

  • Surgery and Imaging: Temporary discontinuation before surgery or contrast-agent-involved imaging is advisable due to acute kidney injury risk.

  • Alcohol: Patients should comprehend potential alcohol interactions that influence blood sugar control.

Source Article IclonSourcesSource Article Arrow
Dr. Raveendran S R
Dr. Raveendran S R



metformintype 2 diabetes mellitus
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