Results strengthen the drug’s potential role in both weight and glycaemic control.
Another major trial of orforglipron has landed, paving the way for Eli Lilly Australia’s upcoming TGA submission.
The latest trial, ATTAIN-2, included more than 1600 adults with obesity and co-existing type 2 diabetes.
Participants were randomly assigned in a 1:1:1:2 ratio to once-daily orforglipron 6mg, 12mg, 36mg or placebo.
Across all doses, weight loss was superior to placebo. Participants assigned to 12mg and 6mg doses achieved a mean weight loss of 7% and 5% respectively, compared to less than 3% in the placebo group.
But the real star was the 36mg dose, which showed the most significant improvements across the board.
The group achieved a mean bodyweight reduction of nearly 10%, with more than a quarter losing at least 15% of their weight from baseline.
More than 67% achieved weight loss of at least 5%, and nearly 46% reduced their bodyweight by 10% or more. Waist circumference was reduced by more than 8cm compared to less than 3cm for the placebo group.
Orforglipron also led to a substantial reduction in glycated haemoglobin (HbA1c) in the 36mg group, with a nearly 2% reduction compared to less than half a percent in the placebo group.
Around 75% of the 36mg group reached an HbA1c less than 7%, a widely accepted treatment target for people with diabetes, compared to around 30% of the placebo group.
The phase three, double-blind, placebo-controlled trial was conducted across ten countries, including Australia, over 72 weeks.
An Eli Lilly spokesperson confirmed with The Medical Republic that orforglipron would be submitted for TGA approval for the management of obesity and overweight by the end of this year.
“Clinically meaningful findings from the orforglipron ATTAIN and ACHIEVE clinical trial programs form the basis of this regulatory submission,” they said.
“Orforglipron is the first oral small molecule (non-peptide) GLP-1 agonist, taken without food and water restrictions, to successfully complete phase 3 trials in both patients with type 2 diabetes and those living with obesity and overweight.
“While unable to comment on when orforglipron may be prescribed to Australian patients, we are committed to working constructively with the Federal Government to ensure that Australians can access the most effective medicines to manage chronic cardiometabolic conditions.
“Lilly also notes the urgent need for reform of Health Technology Assessment in Australia to support more timely and equitable access to innovative medicines through the Pharmaceutical Benefits Scheme.
“Eli Lilly is making substantial global investments to meet anticipated demand for orforglipron at launch.”
Inclusion requirements for ATTAIN-2 were a minimum BMI of 27, HbA1c of 53–86 mmol/mol and pre-existing type 2 diabetes with stable treatment for at least 90 days, including up to three oral antihyperglycaemic medications.
Participants also had to have a history of at least one self-reported unsuccessful dietary effort to lose weight.
Related
Average baseline bodyweight was 101kg, BMI was 36 and HbA1c was 64 mmol/mol. Mean participant age was 57 years, nearly half were female and 71% were white. Median duration of obesity was 16 years, and median duration of diabetes was seven years.
Participants received individualised dietary and exercise counselling throughout the study period alongside treatment or placebo.
Treatment discontinuation due to adverse events occurred in 6% of orforglipron 6mg group, around 9% of 12mg group, 10% of 36mg group and 4% of placebo group.
The overall incidence of reported adverse events was fairly balanced across treatment groups. Serious adverse events were reported by less than a tenth of participants overall, with no significant differences in reporting across groups.
A total of 10 deaths were reported during the study: four in the 12mg group, two in the 36mg group and four in the placebo group.
Of the six deaths in the orforglipron groups, the investigators considered all but one (in the 12mg group) to be unrelated to the study drug. Of the four deaths in the placebo group, all but one (advanced pancreatic cancer) were considered unrelated to study treatment.
