Initial Tirzepatide Data Show Promise as a Diabetes Treatment

Juan Pablo Frías, MD

New topline data shows tirzepatide yielded superior A1C and body weight reductions across 3 separate doses when compared to injectable semaglutide 1 mg in adults with type 2 diabetes.

Eli Lily and Company announced the preliminary data from the 40-week SURPASS-2 trial, where tirzepatide 15 mg reduced A1C by 2.46% and body weight by 27.3 pounds (13.1%), the highest dose tested.

In the 40-week, randomized, open-label trial, the investigators compared the efficacy and safety of tirzepatide to semaglutide as an add-on to metformin in 1879 adults with type 2 diabetes. The mean duration of diabetes for the patients was 8.6 years, with a baseline A1C.

Tirzepatide is a novel, investigational, once-weekly, dual glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 receptor agonist. The drug integrates the actions of both incretins into a single molecule, representing a new class of medicines studies for diabetes treatment.

The Results

A total of 92% of patients in 15 mg group achieved an A1C of less than 7%, the recommended target for individuals with diabetes by the American Diabetes Association, compared to 81% of the patients taking semaglutide.

For the lowest dosing in the trial, researchers found tirzepatide 5 mg reduced A1C by 2.09% and body weight by 17.2 pounds (8.5%), compared to semaglutide at 1.86% and 13.7 pounds (6.7%).

The researchers also found 51% of patients taking tirzepatide 15 mg achieved an A1C of less than 5.7%--which is the level of individuals without diabetes. That number is significantly higher than the comparison group, where just 20% achieved this target A1C.

"Head-to-head studies are the gold standard for clinicians assessing the efficacy of investigational treatments, and these results show that all three doses of tirzepatide delivered superior A1C and weight reductions compared to the highest approved dose of semaglutide to treat type 2 diabetes," said Juan Pablo Frías, MD, Medical Director, National Research Institute and Principal Investigator of SURPASS-2, in a statement.

"Newer treatment options may help people with type 2 diabetes achieve their A1C and weight loss goals. In SURPASS-2, tirzepatide delivered clinically meaningful efficacy, beyond what has been seen with an existing medicine in the established GLP-1 receptor agonist class." Of 8.28% and a baseline weight of 206.6 pounds.

Safety

The overall safety profile of the treatment was similar to previously reported SURPASS trials and the well-established glucagon-like peptide-1 (GLP-1) receptor agonist class. The most common adverse events, regardless of dosage, was gastrointestinal-related, including nausea (17.4% [5 mg], 19.2% [10 mg], 22.1% [15 mg], 17.9% [semaglutide]), diarrhea (13.2% [5 mg], 16.4% [10 mg], 13.8% [15 mg], 11.5% [semaglutide]), and vomiting (5.7% [5 mg], 8.5% [10 mg], 9.8% [15 mg], 8.3% [semaglutide]).

Hypoglycemia less than 54 mg/dl was found in 0.6% of the 5 mg group, 0.2% of the 10 mg group, and 1.7% of the 15 mg arm, as well as 0.4% of the semaglutide arm.

In addition, treatment discontinuation rates due to adverse events were 5.1% (5 mg), 7.7% (10 mg), 7.9% (15 mg), and 3.8% (semaglutide).

The complete data from the SUPASS-2 study will be presented during the upcoming American Diabetes Association’s 81st Scientific Sessions.