Diabetics on Lilly's orforglipron shed 10.5% of their weight

Eli Lilly has reported the results of a third phase 3 trial of oral weight-loss therapy orforglipron, clearing the way for regulatory filings around the world.

The results of the ATTAIN-2 study, which involved people with obesity or overweight with type 2 diabetes, showed that the oral GLP-1 agonist achieved an average weight loss of 10.5% at the highest dose (36 mg once daily) after 72 weeks, and also helped patients improve their blood glucose control.

The readout comes less than three weeks after Lilly saw its share price slump on the results of the ATTAIN-1 study in overweight or obese people with a weight-related health issue, but without diabetes, which revealed a loss of 12.4% at the same time point.

Lilly's stock recovered in the following days as investors came to terms with the result, which was a couple of percentage points lower than hoped, and as the company emphasised the potential of orforglipron to support patients earlier and over a longer period than current injectable weight-loss therapies like Lilly's Zepbound (tirzepatide) and Novo Nordisk's Wegovy (semaglutide).

The new results – in a patient population that is known to find it very difficult to shed weight – helped Lilly's share price firm by just under 2% in pre-market trading at the time of writing.

Orforglipron remains ahead of most potential rivals in the oral category, although, Novo Nordisk filed for approval of an oral version of Wegovy earlier this year that could become the first oral GLP-1 treatment for obesity if the FDA's decision, due before the end of the year, is positive.

Novo Nordisk's marketing application came on the back of the OASIS 4 study, which showed a weight loss of 13.6% with a 25 mg once-daily oral dose after 64 weeks. That was lower than a 15.1% reduction with a 50 mg dose, but that formulation does not appear to have been submitted for approval, potentially because of a less favourable side-effect profile. All GLP-1 drugs are associated with gastrointestinal side effects like nausea and vomiting.

In ATTAIN-2, two lower doses of orforglipron (6 mg and 12 mg) achieved weight loss of 5.5% and 7.8%, respectively, while a placebo group shed 2.2%. Half of all patients on the 36 mg dose met the objective of losing 10% or more weight, and there was a 1.8% reduction for this group in haemoglobin A1c, a biomarker for blood glucose control.

Around 85% of patients on the top dose reduced their A1c level to below 7%, the target for blood sugar-lowering therapy, and in 75% levels were cut to 6.5%.

"Th[is] data show[s] the potential for orforglipron to offer an efficacy, safety, and tolerability profile consistent with the injectable GLP-1 class," said obesity specialist Louis Aronne, a former president of The Obesity Society.

"Orforglipron could help health care providers expand treatment options for patients who prefer oral therapies without compromising clinical results," he added.