Results from the ACHIEVE-5 trial were presented at the American Diabetes Association annual meeting. The trial evaluated the addition of orforglipron to basal insulin in adults with inadequately controlled type 2 diabetes.

Francesco Giorgino, an MD at the University of Bari Aldo Moro in Italy, said, "Second, and of course most importantly, the primary endpoint was met in terms that the additional orforglipron was able to reduce HbA1c more than basal insulin alone. It was actually from baseline a change in A1C of even more than 2%. So people were starting with an HbA1c at baseline of 8.5% and they decreased this by 1.9%, 2.05% with the two highest doses of orforglipron." Participants receiving placebo in the trial experienced a reduction in HbA1c of 0.77% from baseline. The difference in HbA1c reduction between orforglipron and placebo exceeded 1.2%. Participants receiving basal insulin and orforglipron achieved HbA1c targets of less than 7%, equal to or less than 6.5%, and less than 5.7% at higher rates than those receiving insulin alone.

Giorgino said, "So there's an associated reduction in body weight by about 6 kg versus baseline, whereas in the placebo arm with insulin alone, there's a slight increase." The trial did not show an increased risk of hypoglycemia with the combined regimen of basal insulin and orforglipron compared to basal insulin alone. Data showed a numerical reduction in hypoglycemia rates.

Orforglipron is a non-peptide GLP-1 receptor agonist administered orally once daily. Giorgino said, "So orforglipron is of course a GLP-1-based therapy, so it's associated with some incidence of nausea and vomiting, but not much more than what you would expect for a GLP-1-based therapy." He added, "So the mean duration of the disease was about 15 years." Before the addition of orforglipron or placebo, participants underwent intensive force titration of basal insulin to achieve a fasting glucose of less than 100 mg/dL.