In a phase 2 trial of patients with type 2 diabetes, retatrutide provided clinically meaningful glycemic control and “robust reductions in body weight,” researchers report. A single peptide with agonist activity at the glucose-dependent insulinotropic polypeptide (GIP), GLP-1, and glucagon receptors, retatrutide was studied in people with obesity in a phase 2 trial reported in last Thursday’s PNN.
At 42 U.S. research and healthcare centers in 2021-2022, 281 adults aged 18 to 75 years with type 2 diabetes (HbA1c of 7.0% to 10.5%) and BMIs between 25 and 50 were randomized to once-weekly injections of placebo, dulaglutide 1.5 mg, or retatrutide maintenance doses of 0.5 mg, 4 mg (starting dose 2 mg), 4 mg (no escalation), 8 mg (starting dose 2 mg), 8 mg (starting dose 4 mg), or 12 mg (starting dose 2 mg). The primary endpoint was the change in HbA1c from baseline to 24 weeks, and safety was assessed in all participants who received at least 1 dose of study treatment. A secondary endpoint was the change in body weight at 36 weeks.
Over 24 weeks, retatrutide reduced least-squares mean changes from baseline in HbA1c by 0.43% at the lowest doses to 2.02% at the highest dose. The decreases with placebo and dulaglutide were 0.01% and 1.41%, respectively. Body weight at 36 weeks was decreased by 3.19% to 16.94% with retatrutide, 3.00% with placebo, and 2.02% with dulaglutide.
“Mild-to-moderate gastrointestinal adverse events, including nausea, diarrhoea, vomiting, and constipation, were reported in 67 (35%) of 190 participants in the retatrutide groups (from six [13%] of 47 in the 0.5 mg group to 12 [50%] of 24 in the 8 mg fast escalation group), six (13%) of 45 participants in the placebo group, and 16 (35%) of 46 participants in the 1.5 mg dulaglutide group,” the authors write. “There were no reports of severe hypoglycaemia and no deaths during the study.”