Tirzepatide vs Metformin: Efficacy, Dosing, Side effects

Tirzepatide vs Metformin

Tirzepatide vs Metformin is a comparison of the two medicines used to treat diabetic patients.

Tirzepatide is one of the highly potent newly approved diabetes medicines while metformin is one of the most commonly used diabetes drugs worldwide.

Tirzepatide is being tested for the treatment of obesity in diabetic and non-diabetic individuals while metformin is used for the treatment of metabolic syndrome, insulin resistance syndromes, and PCOS (polycystic ovarian syndrome) apart from its use as a diabetes drug.

What is Tirzepatide?

Tirzepatide is a glucose-dependent insulinotropic polypeptide (GIP) and Glucose like peptide 1 (GLP1) receptor agonist.

It is a dual agonist drug which is why it is also known as “twincretin” and is superior in efficacy to the currently available drugs.

It is marketed by Eli Lilly under the brand name “Mounjaro“. Mounjaro is administered as a once-weekly subcutaneous injection.

Mounjaro costs about 1023.04 USD per fill [Ref]

What is Metformin?

Metformin is a biguanide that is also used as an antihyperglycemic drug in the treatment of type 2 diabetes mellitus.

It acts by decreasing intestinal absorption of glucose and by decreasing the production of glucose in the liver.

Metformin is one of the cheapest medicines and prices vary from as low as a few cents per pack to a few dollars per pack per month.

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Tirzepatide vs Metformin: Dosing Schedules



2.5 mg is injected subcutaneously – once a week.

The dose is increased by 2.5 mg every four weeks until the target dose or the maximum dose is achieved.

The maximum dosage is 15 mg once a week.


500mg – twice a day or 850 mg – once daily. The maximum dose is 2550 mg daily in divided doses


500-1000mg orally – once daily. The dose can be given up to 1000 mg twice daily.


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Mechanism of Action of Tirzepatide vs Metformin



Tirzepatide acts by activating both GLP-1 and GIP receptors which are involved in glucose control, the production of insulin, delaying gastric transit time, reducing body weight, and decreasing the production of glucagon.

This co-administration of GLP1 AND GIP receptors results in a significantly increased insulin response.

Metformin acts by decreasing hepatic glucose production, increasing insulin sensitivity, and by decreasing intestinal glucose absorption.

It inhibits the activity of mitochondrial complex 1 thereby causing antidiabetic effects.

Metformin works by inhibiting the production of enzymes required for gluconeogenesis thereby limiting glucose production.

It also increases insulin sensitivity by decreasing fat synthesis and increasing fat oxidation.


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Clinical efficacy of Tirzepatide vs Metformin for type 2 diabetes:

The current data does not contain any head-to-head trials that compare the clinical efficacy of Tirzepatide and Metformin. However, some studies focus on the clinical efficacy of both drugs.

According to the latest ADA recommendations, metformin is classified as one of the highly active antidiabetes medicine while Tirzepatide is a drug with the highest potency compared to all diabetes medicines approved to date.

Efficacy of Type 2 Diabetes Medications (in descending order)



Intermediate potencyDPP-IV Inhibitors
  • Sitagliptin
  • Vildagliptin
  • Linagliptin
  • Alogliptin
  • Saxagliptin
Intermediate to high potencySGLT2 Inhibitors
High potencyMetformin
  • Metformin
  • Pioglitazone
2nd Generation Sulfonylureas
  • Glyburide
  • Gliclazide
  • Glimepiride
High to very highly potencyGLP-1 Receptor agonists
  • Insulin analogs
  • Human Insulin
Very high potencyGIP and GLP-1 Receptor agonists

A clinical trial that compared the effects of Tirzepatide and Semaglutide concluded that Tirzepatide 5,10 and 15 mg were superior to Semaglutide 1 mg a total of 82-86% of participants achieved HbA1c levels of less than 7%.

The study also concluded that Tirzepatide also causes significant reductions in body weight. [Ref]

Another study suggests that Tirzepatide improves beta-cell function and insulin sensitivity and has the potential to reduce disease severity and improve overall metabolic health. [Ref]

Another recent study suggests that obesity and type 2 diabetes are two deeply linked diseases and Tirzepatide has shown significant reductions in both HbA1c and body weight.

It has given favorable outcomes in SURPASS-1 to SURPASS-5 trials and was superior to other drugs such as Semaglutide and dulaglutide. [Ref]




A1C reduction⇓ 1.2%
  • 5 mg: 2.01%
  • 10 mg: 2.24%
  • 15 mg: 2.30%
Weight reduction⇓ 2.7 kg
  • 5 mg: 7.6 kgs
  • 10 mg: 9.3 kgs
  • 15 mg: 11.2 kgs

A study published in the American Journal of Medicine concluded that metformin therapy reduced FPG and HbA1c levels in a dose-dependent manner. Low doses were also seen to provide benefits but maximum doses provided the maximum benefits. [Ref]

Metformin is the most widely prescribed drug as a first-line treatment for prediabetes and type 2 diabetes and its use as a combination therapy with other SGLT-1 inhibitors has also shown beneficial outcomes in the control of hyperglycemia.

The American Diabetes Association (ADA) recommends Metformin as the first-line treatment for type 2 diabetes.

Metformin significantly lowers blood glucose levels but it does not stimulate insulin secretion with no improvements in plasma insulin response to glucose however, Tirzepatide is known to improve insulin secretion and insulin sensitivity.

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Side Effects of Tirzepatide vs Metformin:



Most Common

  • Abdominal pain

Less Common

  • irregular heartbeat
  • Heartburn
  • Skin rash or redness
  • Swelling
  • Nausea or vomiting
  • Blurred vision
  • Chest congestion
  • Cold sweats
  • Depression
  • Fatigue
  • Seizures
Most Common

  • Low blood pressure
  • Diarrhea
  • Nausea
  • Stomach pain

Less Common

  • Weakness
  • Dizziness
  • Irregular heartbeat
  • Muscle pain
  • Hypoglycemia


Disease Interactions:

Metformin may increase your risks of:

  • Lactic acidosis
  • Vitamin B12 Deficiency
  • Hypoglycemia
  • Cardiovascular risk

Tirzepatide may increase your risks of:

  • Thyroid cancer
  • Pancreatitis
  • Acute kidney disease
  • Retinopathy
  • Severe gastrointestinal disease
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Use in Pregnancy and Lactation:

Metformin is probably the only oral medicine used to treat gestational diabetes and type 2 diabetes in pregnancy. (Glyburide can be used rarely).

Tirzepatide has not been studied in pregnancy but is generally considered contraindicated. It should be stopped 12 weeks before a planned pregnancy.


Tirzepatide and metformin, both are beneficial for the treatment of type 2 diabetes mellitus. The absence of head-to-head clinical trials makes it difficult to compare both drugs.

But the present data suggest that Tirzepatide is a new and potentially beneficial treatment for type 2 diabetes and metformin is the most widely used drug for the treatment of prediabetes and diabetes with long-term safety and efficacy.

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What do you think?

Written by Dr. Ahmed

I am Dr. Ahmed (MBBS; FCPS Medicine), an Internist and a practicing physician. I am in the medical field for over fifteen years working in one of the busiest hospitals and writing medical posts for over 5 years.

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