Best Metformin Alternatives For Type 2 Diabetes
Diabetes

7 Best Metformin Alternatives For Type 2 Diabetes

When you are diabetic, you need to be more cautious with consuming medicines. There are 7 other options of Metformin that you should know, Understand more in detail.

May 06, 2021
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Glucophage
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Actos
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Post Highlights

Metformin is the most commonly prescribed medication for the treatment of diabetes. It is also one of the most prescribed drugs globally. As with other drugs, it is possible to experience side effects during the treatment, or the medicine may not be suitable. Metformin can commonly cause gastrointestinal side effects, often leading to switching to another drug.

Let me help you know about the two types of diabetes that a person can face, which is Type1 and type 2 diabetes. Both are considered chronic diseases that will act on glucose production and the sugar you need in the body.

Glucose is the foremost thing that your body cells need, so Insulin is a critical requirement.

  • People who have type1 diabetes don't develop Insulin in the body.
  • For people with type 2 diabetes, glucose does not react to insulin as it should.

These two types of diabetes have harmful effects on the body and can increase blood sugar levels.

Although there are many type-2 diabetic drugs, patients would be offered Metformin alternatives according to the national guidance on managing type 2 diabetes.

Here we will summarise Metformin alternative drugs, which may be prescribed to type 2 diabetic patients who cannot tolerate Metformin.
Terminology Found In This Post

What Is Metformin?

Metformin is generally perceived as a 'gold standard for treating diabetes. Metformin is the only type 2 diabetic drug classified as a biguanide. Newly diagnosed type 2 diabetic patients, particularly overweight, who failed to implement lifestyle changes to control sugar 'level' in the body, usually get prescribed or buy Metformin online. Metformin is marketed under the trade names Glucophage, Glucophage XR, Fortamet, Glumetza, and Riomet.

However, the official guide on managing type 2 diabetes in adults recommends using Metformin as a first-line drug to treat type 2 diabetes.

Metformin can be prescribed independently or in conjunction with other type-2 diabetes drugs. Drugs reviewed in this post can be used as an alternative treatment to Metformin or in conjunction with Metformin if patients fail to control their condition. Metformin can also be prescribed to treat polycystic ovary syndrome.

Metformin: Mechanism Of Action

Metformin has several actions which cause control of glucose (sugars) in the body. It mainly reduces glucose production in the liver and stops glucose from being absorbed in the intestine. Metformin also increases glucose uptake, particularly in skeletal muscle.

Lastly, Metformin improves sensitivity to Insulin (Wiernsperger & Bailey, 1999), which regulates body sugar levels. Metformin does not increase insulin release. Therefore there is no risk of hypoglycemia with Metformin unless used with other antidiabetic drugs.

Metformin Alternatives

1. Lifestyle Changes

Studies have confirmed that it is possible to achieve remission from type 2 diabetes by restricting calorie intake.

According to the twin cycle hypothesis, excess fat in the liver causes an extra supply of fat in the pancreas, leading to impaired organ functioning.

The pancreas produces Insulin which is the key to sugar control in the body.

Reduced intake of calories decreases glucose production and helps lose weight.
The most crucial factor determining the success of remission from diabetes is the duration of the condition. Patients who had type 2 diabetes for less than four years achieved a fast reduction in blood glucose.

On the other hand, only 50% of patients with type 2 diabetes (8 years or longer) reached normal sugar levels with a calorie-restricted diet (Taylo, 2020).

2. Modified-release Metformin Alternative To Standard Metformin

Modified release Metformin (also known as slow or prolonged release) can be offered to patients who cannot tolerate standard release Metformin. Modified-release Metformin provides better gastrointestinal tolerability (Jabbour & Ziring, 2011). Modified-release Metformin can be supplied on a trial basis instead of standard release Metformin to patients who experience gastrointestinal side effects (NICE, 2020).
Modified-release Metformin is usually taken once or twice daily, while standard, immediate-release Metformin can be taken up to three times a day.

Popular brands of modified-release Metformin:

  • Sukkarto SR
  • Glucophage SR
  • Yaltormin SR

A NICE guide on the management of type 2 diabetes (NICE, 2020) recommends mainly three alternatives (classes) of drugs:

  • a dipeptidyl peptidase?4 (DPP?4) inhibitor (gliptins) or
  • pioglitazone or
  • a sulfonylurea

3. Sulfonylurea Type 2 Diabetic Drugs

Sulfonylurea drugs are considered as Metformin alternatives. Commonly sulfonylureas are used together with metformin to control diabetes.

Gliclazide is the most widely used sulfonylurea in the UK (OpenPrescribing.net, 2021).

Gliclazide vs Metformin: what is the difference?

Sulfonylureas like Gliclazide increase insulin release from pancreatic beta cells. Therefore this class of antidiabetic drugs is only practical because pancreatic cells are still present (Sola et al., 2015). Diabetes is a condition that is characterized by progressive loss of insulin-producing ?-cells (Weir GC, Bonner-Weir, 2013).
Overall, Gliclazide has a distinct mechanism of action from Metformin.

Gliclazide vs Metformin: common side effects

British National Formulary (BNF) lists the following possible common side effects:

  • Abdominal pain
  • Diarrhea
  • Hypoglycemia (low sugar level)
  • Nausea

Some common side effects (gastrointestinal) for Gliclazide are similar to Metformin. As previously discussed, hypoglycemia is not a side effect of Metformin treatment.

Other Sulfonylureas are licensed in the UK to treat type-2 diabetes but are less commonly prescribed. These include:

  • Glibenclamide: Glibenclamide is a prescription-only drug. It is commonly known as Glyburide in the USA. Diabeta is the most common name for this medicine.
  • Glimepiride: Glimepiride is less preferred than Metformin as it can lead to weight gain. It is not possible to buy Glimepiride over the counter. The most common Glimepiride brand is Amaryl.
  • Glipizide: Glipizide is often confused with Glibenclamide. The two drugs are different. Glipizide's most common brand is Glucotrol. It was, however, withdrawn in October 2021 in the UK.
  • Tolbutamide: This is a fast-acting Sulfonylureas. The common brand name of Tolbutamide is Orinase. 

4. Gliptins

As per the statistics of openprescribing.net in the period between March 2020 to February 2021, the most commonly used Gliptins drug is Sitagliptin. 

Many people buy Januvia, which is Sitagliptin's most common brand.

The following three drugs were sold after that in the same order.

  • Linagliptin (brand name: Trajenta)
  • Alogliptin (brand name: Vipidia)
  • Saxagliptin (brand name: Onglyza)

Gliptins: mechanism of action

Gliptins (scientific name: DPP-4 inhibitor) enhances insulin secretion in response to glucose presence. Gliptins also reduce the production of glucose by the liver. Gliptins have improved glycemia (presence of sugars in the body) with a low risk of hypoglycemia (Ahrn et al., 2011).

Gliptins: side effects

Gliptins are generally well tolerated. Side effects differ between each gliptin. The table below lists ubiquitous and familiar side effects for each gliptin:

Sitagliptin Headache, Hypoglycemia
Linagliptin Hypoglycemia
Alogliptin Abdominal pain, Gastrooesophageal reflux disease, Diarrhoea, Skin itchiness, Rash, Headache, Hypoglycemia, Increased risk of infection, skin reactions

When used in combination with other antidiabetic drugs, particularly with Insulin and sulphonylurea, but not when used with Metformin. When used in combination with Metformin and sulphonylurea; The low frequency of side effects explains the popularity of Sitagliptin and linagliptin, both prescribed in almost similar volumes.

One of the uncommon side effects that patients need to be aware of (its symptoms) is the risk of acute pancreatitis (inflammation of the pancreas), mainly characterized by persistent, severe abdominal pain. The estimated risk of acute pancreatitis with gliptins is one to two cases for every 1000 patients treated for two years.

5. Metformin Alternatives: Pioglitazone

Pioglitazone tablets: 15mg, 30mg and 45mg.
Pioglitazone is the only thiazolidinedione licensed currently in the UK to treat diabetes. Although considered as a Metformin alternative, Pioglitazone is not commonly used on its own to treat diabetes.

Pioglitazone, however, can be used on its own or in combination with other antidiabetic drugs like Metformin or Sulfonylurea.
Pioglitazone is considered the second or third-line treatment of type 2 diabetes, usually when Metformin is not tolerated or cannot be used (eMC, 2020).

Pioglitazone: side effects

Common side effects associated with pioglitazone use (ibid):

  • Upper respiratory tract infection
  • Hypo-aesthesia (loss of sensation of part of the body)
  • Visual disturbance (usually at the beginning of the treatment)
  • Fracture bone (clinical trial in which 8100 patients took Pioglitazone observed higher rates of bone fractures by women who took Pioglitazone (2.6%), but not men).

Additionally, Pioglitazone was subject to a drug safety update: Pioglitazone: risk of bladder cancer. According to this update and scientific evidence, Pioglitazone is associated with a small increased risk of bladder cancer. There was no evidence to suggest that the same is observed in humans during the approval process for Pioglitazone's license.

As the above document suggests, the evidence for increased cancer risk came from animal studies. European review on Pioglitazone indicates that the benefit of the treatment outweighs the risk, which is 'likely to be small.

There are other special warnings related to Pioglitazone (eMC, 2020):

  • Causing fluid retention, which may exacerbate or precipitate heart failure
  • Caution use with Insulin elderly because of increased risk of severe heart failure
  • Rare incidents of liver dysfunction
  • Weight gain
  • Eye disorders(worsening diabetic macular oedema with decreased visual acuity & ability to recognize shapes)

It is clear from the above why Pioglitazone is not considered the first-line treatment for type 2 diabetes. When looking at prescribing statistics for Pioglitazone, it is clear that this drug is becoming a less popular choice in managing type-2 diabetes.

6. Repaglinide: The Forgotten Metformin Alternative

Interestingly, the NICE guide on type-2 diabetes management mentions repaglinide as a Metformin alternative. As with other options, repaglinide is recommended when Metformin is not tolerated. The NICE guide suggests that repaglinide is equally effective as Metformin and cost-effective.

Repaglinide common side effects:

  • Hypoglycemia
  • Abdominal pain
  • Diarrhea
  • Repaglinide is rarely used in the UK

7. Metformin Alternatives: GLP-1 Agonists

Although the 'official guide does not suggest the drug(s) listed below as Metformin alternatives. Each pill, however, is licensed as monotherapy for type-2 diabetes when Metformin is not tolerated or contraindicated, alone or in combination with other antidiabetic drugs.

Glucagon-like peptide-1 receptor (GLP-1) agonists are a newer class of antidiabetic drugs. All GLP-1 agonists come in injectable pens, except for semaglutide, also available in tablets.

GLP-1 agonist's mechanism of action

GLP-1 agonists have multiple effects on the body (Collins & Costello, 2021):

  • Stimulate insulin secretion
  • Reduce the production of glucagon, which production of glucose in the liver
  • Decrease beta-cell death in the pancreas and promote an increase in their numbers

GLP-1 agonists: common side effects

Common side effects differ between each GLP-1 agonist. Some side effects, for example, gastrointestinal side effects, are similar within the class of GLP-1 agonists. Dulaglutide (the most common GLP-1 agonist) is associated with the following common side effects (eMC, 2021):

  • Hypoglycemia (when used in combination with other antidiabetic drugs)
  • Nausea, diarrhea, vomiting, abdominal pain
  • Decreased appetite
  • Dyspepsia (indigestion)
  • Flatulence (gas production)
  • Constipation
  • Fatigue

GLP-1 agonists have been shown to promote weight loss, lower blood pressure, and total cholesterol (ibid).
GLP-1 agonists prescribed in the UK (in order of popularity*):

  • Dulaglutide (brand name: Trulicity)
  • Liraglutide (brand name: Victoza)
  • Semaglutide (brand name: Ozempic)
  • Exenatide (brand name: Byetta)
  • Lixisenatide (bran name: Lyxumia)
  • based on England's prescribed items between Mar' 20th Feb '21. Data source: OpenPrescribing.net
    Dulaglutide, liraglutide, and semaglutide are considerably more prescribed than the remaining two drugs.

There Are Other Metformin Alternatives

Acarbose

Acarbose is a medication that helps in treating Type2 diabetes. With Acarbose, you can take other medicines too, but under the doctor's vision. Brand name of Acarbose is Precose. Common side effects that you might have is blurred vision and drowsiness. You can get Acarbose from different online pharmacies.

The dosage of Acarbose is mentioned below:

Initial Dose 25mg (Three times a day)
Continuation Dose 50mg to 100mg. 
Maximum Dose 100mg.

Caution: Dosage will differ as per the weight of the person.

Pioglitazone

Pioglitazone helps lower the blood sugar level of people who have Type2 diabetes. You can consume the medication as a combination suggested by your doctor. Generic name of Pioglitazone is Actos. Side effects that you might face are sore throat and tooth problems. For buying Pioglitazone, an online pharmacy could be the best option.

Dosage of Pioglitazone would be:

Initial Dose 15mg to 30mg per day
Continuation Dose 15mg to 45mg per day
Maximum Dose 45mg.

Care that should be taken: Inform your other conditions or sufferings before getting a dosage from a doctor.

Rosiglitazone

Rosiglitazone is a prescribed drug. It helps to treat people who have type 2 diabetes. Possible common effects that can be seen are mild headaches and symptoms of a cold. For getting Rosiglitazone drugs, you can opt for an online pharmacy. The brand name of the medicine is Avandia.

Dosage of the drug are as follows:

Initial Dose 4mg per day
Continuation Dose 8mg (only if the initial dose did not work)
Maximum dose 8mg

For better results: Consume a healthy diet and exercise well.

Albiglutide

Albiglutide is a drug that you can get through injection only. Albiglutide helps in improving blood sugar levels. You can buy the medicine from a doctor's prescription. You can get the medication in a brand name known as Tanzeum. Common side effects that might be seen are nausea and headache.

The dosage that you should take:

Initial dose 30mg once a week
Continuation dose 50mg (if the first dose did not work)
Maximum dose 50mg

Remember: Drink more liquids to keep your kidney working smoothly for the medicine.

Empagliflozin

Empagliflozin drug used in controlling blood sugar levels. It will work better if you have a proper diet and exercise daily. It will prevent you from not suffering from heart attacks or any heart-related issues. Common side effects that can be seen are dehydration and nausea. Other than the brand name Jardiance, you can get Empagliflozin online.

Dosage:

Initial dose 10mg
Continuation Dose 25mg only to people recommended
Maximum Dose 25mg

Caution: You can get infected on your penis or vagina after consuming Empagliflozin.

How To Switch On Metformin Alternative?

If, for some reason, you are looking for an alternate medication to the Metformin, let it be 'you find it not a suitable choice for you or anything like that; never immediately stop taking Metformin and switch to another drug. First, it is recommended to consult your certified family doctor or any doctor. Abrupt discontinuation of Metformin may lead to hyperglycemia. Stop taking medicine abruptly only if it shows to have a side effect or any allergic effects. Always keep in mind that the change in the alternative must be gradual and well planned. Henceforth do plan your treatment accordingly.

Final Words From Druggist

Patients who cannot tolerate or take Metformin have a great choice of Metformin alternative drugs. The most reasonable approach to initial treatment will be to try a modified-release form of Metformin if gastrointestinal side effects are troublesome.
As we learned from this post, many Metformin alternatives may cause similar gastrointestinal side effects as Metformin. Introducing a healthy lifestyle (exercise and diet control) can significantly impact glycaemic management. The selection of the best treatment is based on each patient's circumstances.

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