Metformin/ Glimepiride

Metformin and Glimepiride combination medication is prescribed to help regulate blood sugar levels in individuals with type 2 diabetes mellitus.

Metformin/ Glimepiride

Zoryl M, Glyciphage-VG


Intas Laboratories, Sanofi Aventis

Tablets (SR)

500 mg / 1 mg


Metformin/ Glimepiride


Throughout the history of medicine, few drugs have had much impact as Metformin and Glimepiride. Metformin, derived from the lilac plant, has been used for centuries as a herbal remedy for various ailments. However, its powerful antidiabetic effects were only discovered in the century.

On the other hand, Glimepiride, a third-generation sulfonylurea, emerged later as a breakthrough in diabetes management. These medications together represent a shift in how we treat type 2 diabetes and highlight the vital role of antidiabetic agents in modern medicine.

Given the increasing prevalence of diabetes, a deep understanding of these drugs is crucial. Not do they help control blood sugar levels, but they also play a pivotal role in reducing the risks associated with diabetes complications. Metformin and Glimepiride serve as examples of advancements made in this field.



Composition of Metformin/Glimepiride

Looking into the world gives us valuable insights into the intricate makeup and functions of these medications. Metformin and Glimepiride have chemical structures and properties that determine how they work in our bodies.

Let's start with Metformin, also known as N, N dimethylbiguanide. It may have a structure but it operates through various mechanisms. Its hydrophilic nature makes it safe to use compared to antidiabetic drugs.

On the other hand, Glimepiride belongs to the sulfonylurea class and has a complex chemical name;

  • 1 [[p [2 (3 ethyl 4 methyl 2 oxo 3 pyrroline 1 carboxamido)ethyl]phenyl]sulfonyl] 3 (trans 4 methylcyclohexyl)urea. This class is known for its ability to stimulate insulin secretion. The lipophilic side chains in Glimepiride help it be absorbed better and have a lasting effect making it an effective option, for managing blood sugar levels over time.
  • Moving on from the ingredients Metformin contains metformin hydrochloride while Glimepiride tablets contain glimepiride as their active ingredient. These medications also have ingredients (excipients) that serve specific purposes like improving stability aiding in absorption or controlling drug release. Some common excipients include povidone, magnesium stearate, and microcrystalline cellulose; however, their amounts and specific formulations may vary depending on the manufacturer.

Uses of Metformin/Glimepiride

The introduction of Metformin and Glimepiride in the pharmacology field has revolutionized how diabetes is managed. These medications not play a crucial role in treating Type 2 Diabetes Mellitus (T2DM) but also offer various additional benefits ensuring comprehensive care for diabetic patients.

  • Treating Type 2 Diabetes Mellitus; T2DM is a metabolic disorder characterized by insulin resistance and dysfunction of beta cells. Metformin and Glimepiride effectively combat these issues. Metformin reduces glucose production in the liver and improves insulin sensitivity in skeletal muscles. Its unique mechanism sets it apart from antidiabetic drugs making it the preferred initial treatment option. Glimepiride, on the hand, is a sulfonylurea that stimulates insulin release from pancreatic beta cells. This helps increase insulin levels and improves blood glucose control.(1)
  • Managing Blood Glucose Levels; Hyperglycemia, a challenge for individuals with diabetes, can lead to various complications such as nephropathy and retinopathy. Both Metformin and Glimepiride excel at maintaining optimal blood glucose levels through their yet complementary mechanisms. By working, they can effectively regulate blood sugar fluctuations associated with T2DM providing patients with a sense of metabolic stability.(2)


Blood Glucose Levels

  • Reducing Cardiovascular Risks in Diabetic Patients; Cardiovascular complications remain a cause of illness among people with diabetes. Luckily Metformin and Glimepiride have been found to provide benefits for heart health. Metformin has received praise for its ability to lower the risk of related deaths. This may be attributed to its impact on endothelial function, reduced tendency for blood clotting, and influence on lipid profiles. Similarly, Glimepiride also shows effects on cardiovascular well being potentially due to its multiple beneficial properties, such as improved endothelial function and anti-inflammatory effects.(3)(4)

1. PubMed Central - Glimepiride and Metformin Combinations in Diabetes Comorbidities and Complications: Real-World Evidence

2. SciELO - Metformin plus low glimepiride doses improve significantly HOMAIR and HOMAbCELL without hyperinsulinemia in patients with type 2 diabetes

3. Ocford Academic - Glimepiride use is associated with reduced cardiovascular mortality in patients with type 2 diabetes and chronic heart failure: a prospective cohort study 

4. Science DIrect - Metformin and the heart: Update on mechanisms of cardiovascular protection with special reference to comorbid type 2 diabetes and heart failure

How Metformin/Glimepiride Works

The therapeutic successes of Metformin and Glimepiride are highlighted by their ways of working specifically designed to address the complexities of Type 2 Diabetes Mellitus. Exploring their pharmacodynamics reveals a web of interactions that coordinate their effectiveness.

  • Mechanism of Action in the Body; The core action of Metformin lies in its ability to activate the AMP-activated protein kinase (AMPK) pathway. This activation sets off a chain reaction in metabolic pathways resulting in improved glucose uptake and reduced glucose production. On the hand, Glimepiride belonging to the sulfonylureas class binds to specific receptors on pancreatic beta cells. This binding promotes calcium influx, ultimately triggering a series of events that lead to insulin release.
  • Impact on Insulin Resistance and Pancreatic Beta Cells; Metformin effectively tackles insulin resistance, a major challenge in T2DM. Through its AMPK activation mentioned earlier, Metformin enhances insulin sensitivity in peripheral tissues. At the time, glimepiride's effects stimulate insulin production to compensate for its deficiency seen in T2DM patients. This dual approach aims at improving the condition from different angles.
  • Effects on Liver Glucose Production; Metformin skillfully reduces liver glucose production by inhibiting key enzymes involved in hepatic gluconeogenesis. Doing it helps keep the contribution of liver-derived glucose to overall blood sugar levels under control. This modulation of the liver plays a role in the antihyperglycemic effectiveness of Metformin.

Dosage and Administration

When it comes to determining the dosage for drugs like Metformin and Glimepiride it's important to approach it with care. Individualization becomes crucial in order to maximize the effectiveness of the treatment while minimizing any side effects. Here are some standard dosing recommendations;

1. Metformin is usually started at a dose of 500 mg or twice a day and adjustments are made based on how well your blood sugar levels respond. The maximum daily dose is typically not more than 2000 mg.

2. Glimepiride is typically initiated at a dose of 1 to 2 mg and adjustments are made based on your blood glucose profiles. The highest recommended daily dose is 8 mg. There are factors that need to be considered when adjusting the dosages;

1. Kidney function plays a role, in determining the appropriate Metformin dosage. If you have kidney problems, your doctor may lower the dose. Even discontinue its use.

2. For Glimepiride, extra caution should be taken if you're elderly or underweight to prevent episodes of blood sugar levels (hypoglycemia). Your doctor will tailor your dosage accordingly. Timing and frequency of administration also matter;

1. Metformin has extended-release formulations that allow for daily dosing while immediate-release versions may require splitting the doses throughout the day.

2. Glimepiride has a lasting effect and is usually taken once daily with your first main meal of the day to align with its insulin-secreting effects.

Side Effects of Metformin/Glimepiride

Metformin and Glimepiride have established themselves as components of diabetes management. However, it is crucial to recognize that, like any medication, they can have side effects. Being aware of these side effects, categorized as common and rare, empowers healthcare professionals to anticipate complications and effectively address them.

Common Side Effects

These are the side effects that many patients may experience. They are usually not severe. It can be managed, but it is important to inform and monitor patients about them.

  • Digestive Issues; One commonly reported side effect, especially with Metformin, is gastrointestinal (GI) symptoms. These can include feeling nauseous, vomiting, having an abdomen, or experiencing diarrhea. Fortunately, these symptoms tend to go as the body gets used to the medication.
  • Low Blood Sugar; Both Metformin and Glimepiride can lower blood sugar levels significantly and cause hypoglycemia. Glimepiride is particularly known for its capacity to stimulate insulin production and increase this risk. It is crucial for patients to regularly monitor their glucose levels and learn how to recognize the signs of blood sugar.
  • Skin Reactions: Glimepiride may lead to allergic skin reactions such as rashes, redness, or itching. It's important to distinguish these reactions from skin conditions and address them promptly.

Severe Side Effects

Although it is less common, it is important to monitor and address any serious side effects that may occur.

  • One potential concern with Metformin is the risk of developing a condition called lactic acidosis. This condition involves a decrease in blood pH accompanied by lactate levels. It's crucial to recognize and intervene in such cases as it can be life-threatening.
  • Another issue that may arise, particularly when Glimepiride is taken in doses or combined with other antidiabetic medications is severe hypoglycemia. This requires the administration of glucose and possibly adjusting the medication dosage.
  • Furthermore, although rare, there have been reports of liver or kidney dysfunction associated with these medications, Glimepiride. To prevent health complications, regular monitoring of organ function becomes essential.

Off-label Uses of Metformin/Glimepiride

Apart from their role in managing diabetes, Metformin and Glimepiride have been found to be useful in other medical situations. These off-label uses, while not the intended purposes, highlight the versatility and potential of these medications.

  • Management of Polycystic Ovary Syndrome (PCOS); Metformin, with its ability to make the body more sensitive to insulin, has gained popularity in managing PCOS, a disorder commonly seen among women of reproductive age. By reducing insulin levels, Metformin can help alleviate many symptoms associated with this syndrome including anovulation.
  • Weight. Obesity; Metformin has shown promise in aiding weight loss efforts in individuals with diabetes. Although the exact mechanisms are not fully understood yet, it is believed that Metformin's effects extend beyond controlling blood sugar levels.
  • Potential Cancer Prevention; Early investigations suggest that Metformin may play a role in preventing cancer and serving as a therapy for breast and pancreatic cancers. While it is not currently approved for these uses, this emerging application holds exciting possibilities for future usage of the medication.

Interactions with Other Drugs

The delicate dance of how drugs interact with each other is constant. Requires careful coordination. For established medications like Metformin and Glimepiride, understanding how they work together with other drugs is crucial for maximizing the therapeutic benefits while minimizing potential risks.

  • When combined with medications that lower blood glucose levels, such as DPP 4 inhibitors or GLP 1 agonists, Metformin and Glimepiride can have a stronger effect in lowering blood sugar. This can be used to achieve the desired targets or may require adjusting the dosage to prevent episodes of low blood sugar.
  • There are medications, like NSAIDs, certain antihypertensive, and other sulfonylureas, that can increase the risk of hypoglycemia when taken alongside Glimepiride. Being aware of these interactions is essential to avoid drops in blood sugar levels.
  • Alcohol can Weaken or enhance the hypoglycemic effects of these antidiabetic medications due to its various effects on the body. Beta-blockers can mask blood sugar symptoms, making it harder to recognize its occurrence. Additionally, specific diuretics and corticosteroids may reduce the effectiveness of Metformin and Glimepiride, which might require adjusting their dosage.

Warnings and Contraindications

Metformin and Glimepiride despite their benefits, in managing blood sugar levels have certain considerations and precautions. It is important to be aware of these details to ensure their effective use.


Patients who have impaired liver or kidney function face risks when taking these medications. It is important to monitor and adjust the dosage for patients with liver or kidney insufficiency to prevent adverse reactions, such as lactic acidosis caused by Metformin. It is crucial to inform patients about the danger of combining alcohol with Metformin. Drinking alcohol in excessive amounts increases the risk of lactic acidosis. Patients should be advised to moderate their alcohol consumption and understand the risks associated with this combination.


Severe Kidney Disease; If a patient has kidney impairment, it is not recommended to use Metformin due to the way it is eliminated from the body through the kidneys. Accumulation of the medication can lead to risks and complications.

Metabolic Acidosis; Conditions that cause an increase in acidity in the body, such as acidosis or diabetic ketoacidosis, should be considered as absolute reasons to avoid using Metformin.

Hypersensitivity to Metformin or Glimepiride; If a patient has experienced allergic reactions or hypersensitivity to either Metformin or Glimepiride in the past, it is important to avoid using these medications. Repeated reactions can be more severe and potentially life-threatening.

Careful Administration and Important Precautions

The key to administering drugs effectively is finding the balance between achieving therapeutic benefits and avoiding potential risks. When it comes to Metformin and Glimepiride, this balance becomes more crucial. It requires an understanding of how they should be administered, especially when dealing with vulnerable populations, and taking the necessary precautions accordingly.

Administration to Special Populations

Each patient has a distinct pharmacological profile, and certain groups of people can magnify the differences in drug response. When it comes to patients their advanced age often leads to various physiological changes that affect how drugs are metabolized and how sensitive they are to them.

  • For both Metformin and Glimepiride, it is important to adjust the dosage for elderly patients while closely monitoring for any adverse reactions, especially hypoglycemia. In the case of nursing mothers maintaining a delicate balance between their well-being and that of their unborn or nursing child is crucial.
  • Although there isn't evidence of harm, it is advisable to use Metformin and Glimepiride cautiously during pregnancy considering alternatives when appropriate. Breastfeeding mothers should be aware that while Metformin is generally considered safe, Glimepiride may be passed into breast milk. Caution should be exercised.



  • When dealing with children as patients, there are challenges related to how drugs interact with their developing bodies. While Metformin has been approved for use in pediatric populations, the use of Glimepiride is more limited and requires close supervision along with appropriate dosage adjustments.

children patients

Children patients


In the event of taking too much medication, it is crucial to recognize and manage the situation promptly. The symptoms and signs of an overdose can vary from gastrointestinal issues like nausea to more severe complications such as significant drops in blood sugar levels accompanied by neurological problems.

In some cases, lactic acidosis may occur when taking Metformin, which can be identified by experiencing difficulty in breathing, rapid breathing, and a decrease in blood pH. To address an overdose right away, it is important to stop taking the medication and seek immediate medical assistance. If there is a drop in blood sugar levels, it is vital to quickly supplement with glucose. In cases of acidosis, urgent hospitalization may be necessary, along with the potential need, for hemodialysis.

Handling Precautions

Ensuring the safety of pharmaceuticals is crucial, particularly when individuals like children or pets are in the household. Here are some important guidelines for handling medications

1. Safe Storage and Disposal; Always keep medications in their containers and store them out of reach of children. When medications expire or are no longer needed, it's important to dispose of them. You can. Utilize community take-back programs or follow the instructions provided on the packaging for safe disposal.

2. Preventing Accidental Ingestion: child packaging for medications is essential as an extra precautionary measure. Additionally, it's important to educate all family members about the significance and potential risks associated with these medications to minimize the chances of ingestion. By following these measures, we can ensure an environment when handling medications at home, especially when there are vulnerable individuals such as children or pets involved.

Storage Information

The quality and effectiveness of any medication are closely tied to how it's stored. Proper storage conditions are crucial to maintaining the potency and safety of Metformin and Glimepiride.

  • It is best to store them in a dry place, preferably at room temperature (around 20 25°C or 68 77°F). Avoid storing them in areas with humidity, such as bathrooms or kitchens. Remember, it's important not to consume medications beyond their expiration date.
  • The expiration date indicates not the effectiveness but also the safety of the medication, as using degraded products can be harmful.
  • To protect these medications, from degradation caused by light exposure, it is wise to store them in their original opaque containers. Always ensure that the container is tightly sealed to prevent moisture and potential contaminants from entering.

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