A mainstay of diabetes management for many has always been insulin. Insulin is an incredibly effective way to control blood sugar levels, but in recent years, several other medications for managing diabetes have hit the market. One such drug is tirzepatide, sold under the brand names Mounjaro and Zepbound. Perhaps you have heard of these medications before, be it for the treatment of diabetes or weight loss.

With the wide array of antidiabetic agents on the market, what medication is right for you? This decision will be made by your doctor after a careful review of your medical history and disease presentation. Regardless, you may still be wondering what exactly the differences are between the two popular antidiabetic therapies: tirzepatide and insulin glargine. This article will help to elucidate these similarities and differences so that you can make more informed and educated decisions about your health.

What is tirzepatide?

Tirzepatide is a drug approved by the Food and Drug Administration (FDA) for two separate indications. These indications are approved and marketed under separate brand names and are as follows:

  • Mounjaro: Mounjaro is approved to control blood sugar levels in individuals with type 2 diabetes mellitus in combination with diet and exercise.
  • Zepbound: Zepbound is approved for chronic weight management in adults who are either obese (defined as a body mass index [BMI] of 30 kg/m2 or more) or overweight (defined as a BMI of 27 mg/kg2 or more) with at least one weight-related condition (e.g., high blood pressure, obstructive sleep apnea, dyslipidemia, cardiovascular disease, or type 2 diabetes mellitus) in combination with diet and exercise.

Because the two brand names contain the same active ingredient, sometimes providers will use one “off-label”, meaning it’s used for a non-approved indication. For example, a healthcare provider may prescribe Mounjaro “off-label” for weight loss, because the brand Mounjaro is not FDA-approved for this indication. Its active ingredient, tirzepatide, is however under the brand name Zepbound.

How does tirzepatide work?

Tirzepatide has potent activity in both type 2 diabetes and weight loss due to its dual mechanism of action as a glucagon-like peptide 1 (GLP-1) receptor agonist and a gastric inhibitory polypeptide (GIP) agonist.

Recall that type 2 diabetes is characterized by a lack of insulin production or the body’s inadequate response to insulin. When insulin is lacking, the body can not properly regulate its blood sugar levels appropriately. Through these two mechanisms, tirzepatide helps this deficit by activating pancreatic insulin release, thereby keeping blood sugar levels within range.

Tirzepatide has additional activity by slowing gastric emptying. When you ingest food, it moves through your digestive tract. This process is referred to as gastric emptying. Tirzepatide slows down this process, so you end up feeling fuller and more satiated for longer. In turn, you consume less food, thus losing weight in the process.

How efficacious is tirzepatide?

The efficacy of tirzepatide, particularly in diabetes, has been studied across a variety of treatment settings. The SURPASS trials are a series of studies that have evaluated tirzepatide’s effects on diabetes alone or in conjunction with other treatment modalities, including as monotherapy and in combination with sulfonylureas, metformin, sodium-glucose co-transport 2 (SGLT2) inhibitors, and different types of insulin. To start understanding its effects, let’s review the results from tirzepatide therapy alone.

SURPASS-1: Tirzepatide monotherapy

This study lasted 40 weeks and enrolled 478 patients who were randomized to either placebo or Mounjaro 5 mg, Mounjaro 10 mg, or Mounjaro 15 mg once weekly in addition to diet and exercise. Mounjaro therapy alone caused statistically significant decreases in hemoglobin A1c (HbA1c) versus placebo. It induced reductions in HbA1c of 1.8, 1.7, and 1.7 percent for Mounjaro 5, 10, and 15 mg, respectively, versus only 0.1 percent with placebo. Additionally, participants achieving an HbA1c of less than seven percent were 82, 85, and 78 percent with Mounjaro 5, 10, and 15 mg versus only 23 percent with placebo.

How does tirzepatide compare with insulin glargine?

Now, we know that tirzepatide is effective versus placebo in treating diabetes. But how does it stack up against other antidiabetic agents, like insulin? The SURPASS-4 trial aimed to answer this question. This study lasted 104 weeks and included over 2,000 adult participants with both type 2 diabetes and an elevated cardiovascular risk. Patients received either Mounjaro 5 mg, Mounjaro 10 mg, or Mounjaro 15 mg once weekly or insulin glargine 100 units/mL once a day. Participants were allowed to be on background therapy with either metformin, SGLT2 inhibitors, or sulfonylureas.

Results indicated that Mounjaro at doses of 10 and 15 mg once weekly for a period of 52 weeks caused statistically significant decreases in HbA1c versus once daily administration of insulin glargine. HbA1c decreases were 2.1, 2.3, and 2.4 percent for Mounjaro 5, 10, and 15 mg versus 1.4 percent with insulin glargine. Additionally, subjects achieving an HbA1c of less than seven percent were 75, 83, and 85 percent with Mounjaro 5, 10, and 15 mg versus only 49 percent with insulin glargine. Likewise, based on these results, we can see that Mounjaro therapy is more efficacious than insulin glargine.
What are other notable differences between Mounjaro and insulin glargine?

Aside from clear differences in efficacy, there are notable differences between these two medications about their dosing, side effect profile, and more. Let’s review.

Indication

While both Mounjaro and insulin glargine are referred to as antidiabetic medications, it is important to distinguish what types of diabetes they treat. Mounjaro only treats type 2 diabetes mellitus, the most common form of diabetes and one that typically presents later in life (although more and more children and adolescents are being diagnosed with diabetes each year). It does not treat type 1 diabetes. This is because, in type 1 diabetes, the pancreas makes very little or no insulin at all. Thus, stimulating pancreatic insulin release via Mounjaro’s mechanism of action will not work in these patients.

Alternatively, insulin glargine can be used in both type 1 and type 2 diabetes. Insulin glargine is a type of long-acting insulin that mimics insulin made by the body. For that reason, it can supplement insulin in both type 1 and type 2 diabetics.

Dosing

First and foremost, Mounjaro is given as a once-weekly injection into the thigh, abdomen, or upper arm. The starting dose for Mounjaro is 2.5 mg, after which the dose can be titrated up in 2.5 mg increments every four weeks to a maximum dose of 15 mg weekly. It can be administered at any time of day, with or without regard to meals. The once-weekly dosing is very convenient for patients, as it is not something they necessarily have to remember to do daily.

Insulin glargine differs in that it is a once-daily injection. It can be administered at any point during the day; however, it should be given at the same time every day. The starting dose for insulin glargine in individuals with type 2 diabetes not currently on insulin is 0.2 units/kg daily or up to 10 units daily. The dose will need to be adjusted based on your particular metabolic needs and therapy response.

Side effects

Common side effects experienced with tirzepatide, occurring in more than five percent of individuals, are typically related to the gastrointestinal (GI) tract. These include things like nausea, vomiting, diarrhea, constipation, indigestion, low appetite, and stomach pain. It can also cause injection site reactions, allergies, hair loss, fatigue, and gastroesophageal reflux disease (GERD). Alternatively, insulin glargine can cause things like low blood sugar, injection site reactions, rash, allergic reactions, swelling, weight gain, and lipodystrophy (fat loss).

The two drugs also have varying warnings and precautions associated with their use. Some warnings associated with tirzepatide therapy include:

  • Pancreatitis (inflammation of the pancreas)
  • Severely low blood sugar
  • Allergic reactions
  • Acute kidney injury
  • Complications of diabetic retinopathy
  • Acute kidney injury
  • Serious gastrointestinal (GI) disease

Some warnings associated with insulin glargine include:

  • Dangerously low blood sugar
  • Allergy
  • Dangerously low potassium levels
  • Changes in blood sugar with changes in insulin requirements
  • Fluid retention and heart failure when used with thiazolidinediones

Conclusion

In summary, there are several distinct differences between tirzepatide and insulin glargine therapies. Tirzepatide can be used to treat type 2 diabetes and for chronic weight management. Alternatively, insulin glargine is indicated for both type 1 and type 2 diabetes and is not indicated for weight.

Another key difference is that tirzepatide is administered as a once-weekly injection, while insulin glargine is given as a once-daily injection. Thus, tirzepatide may provide greater convenience for patients with a less frequent dosing schedule.

Finally, one trial compared tirzepatide therapy to insulin glargine therapy in individuals with diabetes. Those patients on tirzepatide demonstrated increased efficacy on parameters such as HbA1c decreases and percent of patients achieving an HbA1c of less than seven percent. Thus, if choosing between the two options, individuals may see more robust results with tirzepatide.