From the Guidelines
Tirzepatide should not be used as a first-line treatment for type 2 diabetes due to its lack of proven benefits in reducing all-cause mortality and major adverse cardiovascular events (MACE) compared to other available treatments, such as SGLT2 inhibitors and GLP-1 agonists 1.
Key Points
- Tirzepatide is a dual GIP and GLP-1 receptor agonist used for treating type 2 diabetes and obesity.
- The medication has a typical starting dose of 2.5 mg injected subcutaneously once weekly, with a maintenance dose of 5,10, or 15 mg weekly based on glycemic control and tolerability.
- Common side effects of tirzepatide include nausea, vomiting, diarrhea, and decreased appetite, which often improve over time.
- According to recent studies, SGLT2 inhibitors and GLP-1 agonists have been shown to reduce all-cause mortality and MACE in adults with type 2 diabetes, whereas tirzepatide has not demonstrated these benefits 1.
Clinical Considerations
- Patients with a history of pancreatitis, medullary thyroid cancer, or multiple endocrine neoplasia syndrome type 2 should avoid using tirzepatide.
- Glycemic control efforts should be tailored to individualized goals for A1C, with a recommended goal between 6.5% and 7.0% for most persons with type 2 diabetes.
- Combination therapy with agents having complementary mechanisms of action, such as GLP-1 RAs and SGLT2 inhibitors, may be beneficial for many individuals with type 2 diabetes.
- The choice of antihyperglycemic therapy should be based on the individual's characteristics, preferences, and access to therapies, as well as the strength of cardiovascular outcomes trial (CVOT) evidence of benefit 1.
From the FDA Drug Label
The FDA drug label does not answer the question.
From the Research
Overview of Tizepatide
- Tizepatide, also known as tirzepatide, is a dual GIP/GLP-1 receptor co-agonist approved for the treatment of type 2 diabetes in the USA, Europe, and the UAE 2.
- It is an acylated peptide engineered to activate the GIP and GLP-1 receptors, key mediators of insulin secretion that are also expressed in regions of the brain that regulate food intake.
Efficacy of Tizepatide
- Five clinical trials in type 2-diabetic subjects (SURPASS 1-5) have shown that tirzepatide at 5-15 mg per week reduces both HbA1c (1.24 to 2.58%) and body weight (5.4-11.7 kg) by amounts unprecedented for a single agent 2.
- A sizable proportion of patients (23.0 to 62.4%) reached an HbA1c of < 5.7% (which is the upper limit of the normal range indicating normoglycaemia), and 20.7 to 68.4% lost more than 10% of their baseline body weight 2.
- Tirzepatide was significantly more effective in reducing HbA1c and body weight than the selective GLP-1 RA semaglutide (1.0 mg per week), and titrated basal insulin 2, 3, 4.
Safety of Tizepatide
- Adverse events related to tirzepatide were similar to what has been reported for selective GLP-1RA, mainly nausea, vomiting, diarrhoea, and constipation, that were more common at higher doses 2, 5, 6.
- Cardiovascular events have been adjudicated across the whole study program, and MACE-4 (nonfatal myocardial infarction, non-fatal stroke, cardiovascular death and hospital admission for angina) events tended to be reduced over up to a 2 year-period, albeit with low numbers of events 2.
- The safety profile of tirzepatide was consistent with GLP-1 receptor agonists, indicating a potential monotherapy use of tirzepatide for type 2 diabetes treatment 6.
Clinical Trials
- The Phase 3 SURPASS 1-5 clinical trial programme was designed to assess efficacy and safety of once-weekly subcutaneously injected tirzepatide (5,10 and 15 mg), as monotherapy or combination therapy, across a broad spectrum of people with type 2 diabetes 3, 4.
- The SURPASS-1 trial showed that tirzepatide monotherapy was superior to placebo for changes from baseline in HbA1c, fasting serum glucose, bodyweight, and HbA1c targets of less than 7.0% (<53 mmol/mol) and less than 5.7% (<39 mmol/mol) 6.