Metformin vs Insulin: Uses, Differences, Side Effects

Insulin and metformin are some of the better-known types of diabetes medications, but how do they stack up against one another? 

We’ll compare the effectiveness, side effects, pros, cons, and more of metformin vs insulin in this article!

What is metformin?

Metformin is one of the most commonly prescribed medications for type 2 diabetes. It’s considered a first-line therapy, which means most patients diagnosed with type 2 diabetes start metformin as their first diabetes medication.

Metformin is the generic name that is most commonly prescribed because it is the most affordable for most patients, but the brand names Glucophage, Glumetza, and Fortamet might also be used. 

Metformin is taken orally in the form of tablets, with a typical dosing range between 500-2,550 milligrams daily. 

There are two types of metformin, regular and extended-release (XR). The extended-release version is only taken once daily and breaks down more slowly, which can reduce side effects for some patients.

Metformin is in a drug class called biguanides. Biguanides help reduce the amount of sugar your liver makes (gluconeogenesis) while improving insulin sensitivity, which helps reduce high blood sugar. 

Metformin doesn’t cause low blood sugar (hypoglycemia), which is one of its major benefits. Because it doesn’t cause low blood sugar, people with type 2 diabetes can take metformin along with other medications like sulfonylureas and injectable insulin.

While metformin is most commonly used for type 2 diabetes, it’s also used “off-label” to help treat polycystic ovarian syndrome (PCOS), a hormonal disorder in women often stemming from insulin resistance. 

What is insulin?

Insulin is a hormone that a healthy pancreas without diabetes produces through its beta cells. Insulin lowers blood sugar levels by allowing the sugar to enter your body’s cells.

With type 1 diabetes, the beta cells are destroyed by your immune system, and you no longer produce enough insulin. With type 2 diabetes, you become insulin resistant, and your body doesn’t respond to insulin effectively. Over time, you can become insulin deficient.

Injectable insulin is made by inserting a gene that codes for the insulin protein into either yeast or bacteria. 

Up until 2006, medical insulin was primarily made from the pancreas of pigs, but it’s becoming less common with the use of newer techniques. 

Insulin is primarily injectable (except powdered insulin that can be inhaled, which isn’t very common) and is meant to be injected into the subcutaneous tissue. There are several types of insulin, which we’ll cover below.

Injectable insulin is approved for use in type 1 diabetes, type 2 diabetes, and gestational diabetes.

Basal/long-acting insulin

Long-acting insulin helps mimic your body’s “basal” insulin production. This is the slow, consistent release of insulin throughout the day. 

Long-acting insulin isn’t the same as short- and rapid-acting insulin, which works faster and doesn’t last as long.

Long-acting insulin is usually injected once or twice daily in the morning and at bedtime. In general, long-acting insulin lasts up to 24 hours after you inject it. Newer “ultra-long acting” insulins can last longer than that.

Insulin is available in vials, where you draw up your dose with a syringe, or in prefilled injector pens. The latter tends to be more convenient for most patients, but some people might prefer to use insulin vials and draw up their dose.

Here are some common types of long-acting insulin:

Lantus

One of the most common types of long-acting insulin, Lantus is the brand name for insulin glargine. 

Lantus was approved by the United States Food and Drug Administration (FDA) in 2000 and is usually injected once daily. 

Some patients might split their Lantus dose among morning and nighttime doses if they’re experiencing hypoglycemia (low blood sugar), especially overnight.

Levemir

Levemir is the brand name for insulin detemir. This type of insulin doesn’t typically last as long as Lantus in terms of duration, so it is more common for Levemir to be injected twice daily compared to Lantus, which is more often injected just once daily. The United States FDA approved Levemir in 2005.

Semglee

Semglee is a brand name for insulin glargine-yfgn, a newer type of long-acting insulin that was approved by the FDA in 2020. 

Glargine-yfgn is considered biosimilar to insulin glargine (Lantus), so Semglee and Lantus are considered interchangeable. 

Toujeo

Toujeo is a concentrated form of long-acting insulin with the same active ingredient as Lantus (insulin glargine) that has been approved since 2015. 

However, instead of the normal 100 units per milliliter concentration, Toujeo is more concentrated at 300 units per milliliter, which is a perk if you take a large amount of insulin.

Toujeo also has a longer shelf life compared to Lantus (up to 8 weeks for Toujeo compared to 28 days for Lantus), so it can be more cost-effective by not having to throw away expired insulin. 

Basaglar

Basaglar’s active ingredient has a similar chemical structure as Lantus (insulin glargine), but it isn’t considered interchangeable because it is made differently than Lantus. 

You can expect similar results when using Basaglar as you do with Lantus, but you might not be able to seamlessly switch from one type to the other since they aren’t considered interchangeable. Basaglar was FDA-approved in 2015.

Tresiba

Tresiba is the brand name for insulin degludec. It is a newer long-acting insulin that was approved in 2015. 

Tresiba should last even longer than Lantus and Levemir – at least 42 hours, according to the manufacturer. 

Tresiba medication is available in 100 units/mL and 200 units/mL concentrations, whereas Lantus and Levemir are only available in 100 units/mL concentrations.

Bolus/short-acting insulin

Bolus or short-acting insulin starts to work more quickly than long-acting insulin and doesn’t work as long (duration time) to lower your blood sugar levels. Bolus insulin is also called mealtime insulin and is generally injected before eating.

This type of insulin is either short-acting or rapid-acting.

Short-acting insulin starts to work around 30 minutes after you inject it, peaks around 2-3 hours after injection, and lasts around 3-6 hours after injection.

Rapid-acting insulin starts to work even faster, around 15 minutes after you inject it. It lasts around 2-4 hours and peaks around one hour after injection.

Short- and rapid-acting insulin comes with a higher risk of hypoglycemia because they work to lower your blood sugar in a shorter period. 

That means that if you inject bolus insulin and don’t eat a meal, your blood sugar might fall too low.

Here are some common short- and rapid-acting insulins:

Humulin R or Novolin R

Also called regular insulin, this type of insulin is considered short-acting and should be injected around 30 minutes before you begin a meal. 

Regular insulin lasts around 5-8 hours and peaks around 2-3 hours after you inject it.

Novolog (insulin aspart)

Novolog is a type of rapid-acting insulin that begins to work around 15 minutes after injection, peaks around one hour after injection, and lasts for about 3-5 hours.

Humalog (insulin lispro)

Humalog peaks around 1-2 hours after you inject it and lasts for around 2-4 hours. Like Novolog, you should inject Humalog within 15 minutes of starting a meal or immediately after finishing a meal.

Apidra (insulin glulisine)

Apidra is a newer rapid-acting insulin that should be injected 15 minutes before eating or within 20 minutes of starting a meal. It has a similar peak time and duration as Humalog.

Intermediate-acting insulin

Intermediate-acting insulin starts to work around 2-4 hours after injection and has a duration of around 12-18 hours, peaking around 4-12 hours after injection. 

This type of insulin is usually injected twice daily (morning and night) or once daily at bedtime.

NPH insulin (Insulin human isophane)

Intermediate-acting insulin is sold under many brand names such as Humulin N and Novolin N.

Premixed insulin

Premixed insulin contains a mix of either short or rapid-acting insulin and intermediate-acting insulin (NPH). 

There are several types of premixed insulin, but they are generally injected 15-20 minutes before a meal, 2-3 times per day.

Insulin pump therapy

Insulin pumps are especially popular among patients with type 1 diabetes. An insulin pump delivers insulin automatically based on the preferences set by the user. 

Insulin pumps reduce the need for multiple injections and can be paired with continuous glucose monitors to reduce fingersticks and the need to check blood sugar levels several times per day.

Does metformin work the same as insulin?

No. Metformin works differently than insulin. Metformin doesn’t increase insulin production, nor does it provide insulin as injectable insulin does.

Instead, metformin works to reduce the amount of sugar made by your liver and can help with insulin resistance. 

Unlike insulin, metformin doesn’t come with the risk of low blood sugar, which is one of its significant benefits.

Metformin vs insulin uses

In general, metformin is used as a first-line treatment for type 2 diabetes and can be combined with several other diabetes medications.

Insulin is used as the primary treatment for patients with type 1 diabetes, but it can also be used in patients with type 2 diabetes who aren’t reaching their blood sugar target on non-insulin medications. 

It’s also ideal for patients with “type 1.5 diabetes”, which is type 2 diabetes that is more similar to type 1 because there is an element of insulin deficiency.

	Metformin	Insulin
Used for type 1 diabetes	Not generally, but can be used to reduce insulin requirements in some patients	Yes, as the sole treatment
Used for type 2 diabetes	Yes, primarily	Yes
Used for gestational diabetes	Yes	Yes
Approved for children as young as 2	No (minimum age is 10)	Yes, but can depend on the specific type
Used in very elderly/high-risk for low blood sugar patients	Yes	No

Effectiveness 

Insulin tends to be the most effective at lowering blood sugar levels, but it comes with the risk of hypoglycemia (low blood sugar). 

If your blood sugar levels aren’t well-controlled on other medications, your healthcare provider will likely recommend you start taking insulin, especially if your hemoglobin A1c is greater than 9% (which indicates poor blood sugar control).

Metformin tends to lower hemoglobin A1c by around 1%, whether used alone or with another diabetes medication. This is according to a meta-analysis of 35 studies, each lasting at least 12 weeks.

Insulin therapy tends to lower A1c more significantly than 1%, but because the dosages and schedules of insulin therapy vary so much, it’s more difficult to quantify typical results/effectiveness.

Side effects

In this section, we compare the side effects of metformin vs insulin.

Metformin

The most common side effects of metformin include:

• Heartburn
• Stomach pain
• Nausea or vomiting
• Bloating
• Gas
• Diarrhea
• Constipation
• Weight loss
• Headache
• Metallic taste in your mouth

If you take very large doses of metformin, you might develop lactic acidosis, a rare but serious health condition. The prevalence of lactic acidosis is very low and extremely rare.

Insulin

The potential side effects of insulin are similar regardless of the type and include:

• Low blood sugar (hypoglycemia), which is when your blood sugar is less than 70 mg/dL
• Allergic reactions
• Injection site reactions
• Changes in body fat distribution (lipodystrophy), one of the more common complications of injecting insulin
• Itching
• Rash
• Fluid retention (edema)
• Weight gain

Benefits of metformin vs insulin

Below, we compare the benefits of metformin vs insulin.

Benefits of metformin

• Doesn’t cause low blood sugar
• No injections (good for patients with a fear of needles)
• Can be combined with many other diabetes medications
• Suitable for elderly patients and other patients at high risk of hypoglycemia
• Safe and effective first-line treatment for type 2 diabetes

Benefits of insulin

• Very effective at lowering blood sugar levels and reducing A1c
• Only type of diabetes medication effective in treating type 1 diabetes
• Dose can be tailored to your needs, such as adjusting mealtime insulin dose based on what you eat
• Comes with fewer side effects such as stomach upset, etc. that metformin can cause

FAQs

Conclusion

This article compared two diabetes medications, metformin vs insulin. Metformin is a type of medication used to treat type 2 diabetes. Insulin is a different type of medication that is also used to treat type 2 diabetes as well as type 1 diabetes.

The main advantage of metformin is that it doesn’t cause low blood sugar, while the main advantage of insulin is that it is very effective at lowering blood sugar (but comes with a risk of low blood sugar).

Metformin and insulin can be used together, which has benefits for the treatment of type 2 diabetes.

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