Tizepatide shows efficacy and safety in diabetes treatment

Article by Bruce Sylvester.

Investigative tirzepatide appears to improve glycaemic control and bodyweight in Type 2 diabetes patients, without raising the risk of hypoglycemia.

Researchers reported these findings on June 26, 2021 in The Lancet.

As background to the phase 3 study, the authors noted, “Analogues of the incretin GLP-1 have helped to transform the face of type 2 diabetes treatment, combining effective reductions in glycaemia with clinically useful weight loss. More importantly, GLP-1 analogues are proven to reduce mortality, the risk of cardiovascular events, and progression of diabetic kidney disease. However, the achievable doses and efficacy of GLP-1 analogues can be limited by their adverse effects, mainly gastrointestinal in nature, such as nausea, vomiting, gastro-oesophageal reflux, and alterations in bowel habit. In the search for the next step beyond GLP-1, researchers have explored suitable companion treatments to obtain enhanced efficacy.” 

Tirzepatide is a dual agonist of GLP-1 and GIP receptors.

The researchers conducted a 40-week, double-blind, randomized, placebo-controlled, and international phase 3 trial (SURPASS-1).

They enrolled adult subjects (≥18 years) diagnosed with type 2 diabetes inadequately controlled by diet and exercise alone, and who were naive to injectable diabetes therapy.

From June 3, 2019, to Oct 28, 2020, they enrolled 478 subjects with a mean baseline HbA_1c of 7.9% and a mean age of 54 years. There were 231 (48%) female subjects. Mean diabetes duration was 4.7 years, and mean body-mass index was 31.9 kg/m^2..

The subjects were randomized to once-weekly injections of tirzepatide 5 mg (n=121), tirzepatide 10 mg (n=121), tirzepatide 15 mg (n=121) or placebo (n=124).

The primary endpoint was mean change in glycated hemoglobin (HbA_1c) at 40 weeks from baseline.

Subjects on each dose of tirzepatide achieved superior reductions in glycated hemoglobin (HbA_1c) when compared to placebo. Estimated mean treatment differences versus placebo were −1.91% with tirzepatide 5 mg, −1.93% with tirzepatide 10 mg and −2.11% with tirzepatide 15 mg, a statistically significant for all doses (p<0·0001).

Notably, among subjects on the 15 mg dose of tirzepatide, 52% achieved an HbA_1c target of less than 5.7%. And 86% achieved an HbA_1c of 6.5% or less without any clinically significant hypoglycemia.

Tirzepatide treatment induced a dose-dependent bodyweight loss from 7.0 to 9.5 kg.

Most common adverse events were gastrointestinal and dose-dependent, including mild to moderate nausea (18% in the group receiving 15 mg), diarrhea (12% in the group receiving 15 mg), and vomiting (6% in the group receiving 15 mg).

The authors concluded, “Tirzepatide showed robust improvements in glycaemic control and bodyweight, without increased risk of hypoglycaemia. The safety profile was consistent with GLP-1 receptor agonists, indicating a potential monotherapy use of tirzepatide for type 2 diabetes treatment.”