In type 2 diabetes with increased CV risk, tirzepatide reduced HbA1c vs. glargine at 52 wk
Once tirzepatide is approved by the FDA, it may be a treatment option for patients with type 2 diabetes who are overweight, have high risk for atherosclerotic cardiovascular (CV) disease, and have no gastrointestinal symptoms, an ACP Journal Club summary said.
An international, industry-funded phase 3 trial found better glycemic control with the novel dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist tirzepatide than with insulin. The trial included patients with type 2 diabetes treated with any combination of metformin, sulfonylurea, or a sodium-glucose co-transporter-2 (SGLT2) inhibitor who had established cardiovascular (CV) disease or a high risk of CV events. They were randomized to one of three doses of tirzepatide or insulin glargine; at 52 weeks, the investigational drug had met the noninferiority margin.
The study was published online by The Lancet on Nov. 13, 2021. The following commentary by Madhusree Singh, MD, was published in the ACP Journal Club section of Annals of Internal Medicine on March 1.
Once licensed for use, tirzepatide will be one of several newer medications for type 2 diabetes. The findings of the SURPASS-4 trial by Del Prato and colleagues show that, compared with add-on glargine, add-on tirzepatide reduced HbA1c and weight without causing clinically important hypoglycemia, although patients had more nausea and vomiting. Where it fits in the pharmacopeia may be for a patient with type 2 diabetes who is overweight, has high risk for atherosclerotic CV disease, and no gastrointestinal symptoms. Tirzepatide may offer an alternative to glucagon-like peptide-1 receptor agonists (GLP-1 RAs); however, side effects may be greater with this agent.
The CV safety profile seems acceptable in this cohort at high CV risk, but no CV benefit was shown, at least for the median 85 weeks of study. There are good long-term studies showing CV outcome benefits with SGLT2 inhibitors and GLP-1 RAs; longer-term data of major CV events for tirzepatide are needed. In patients with heart failure and impaired kidney function, it is also unknown if tirzepatide has comparable CV benefits to SGLT2 inhibitors.
In an overweight person with type 2 diabetes that is not well controlled, tirzepatide may be another choice if GLP-1 RAs are not a good option, but gastrointestinal symptoms may increase with higher doses of tirzepatide. The cost of the drug will be a factor in prescribing as well. We need comparative studies of GLP-1 RAs and SGLT2 inhibitors vs. tirzepatide to better assess when each drug should be prescribed. A patient with upper gastrointestinal symptoms will probably not be a good candidate for this drug, at least at the higher doses.