New diabetes drugs took centre stage at this month’s American Diabetes Association Scientific Sessions in New Orleans, with a wave of newer candidates and next-generation formulations overshadowing established players such as semaglutide and tirzepatide.
Among the headline results, Eli Lilly’s experimental oral drug orforglipron beat oral semaglutide on blood sugar control and weight loss in head-to-head trial results.
The phase 3 ACHIEVE 3 trial, published in The Lancet [link here], tested a 36mg dose of orforglipron against oral semaglutide in patients with type 2 diabetes whose blood sugar was not adequately controlled by metformin alone.
After a year, patients on orforglipron had their HbA1c reduced by 1.9%, compared with 1.5% for those on semaglutide. Weight loss was 8.2% versus 5.3%, the trial found. However, more patients on orforglipron reported gastrointestinal side effects, and the drug was linked to a slightly greater increase in heart rate.
Lead author Professor Julio Rosenstock, from the University of Texas, said the results supported orforglipron as another oral treatment option for patients with type 2 diabetes.
Cagrisema linked to diabetes remission
Two phase 3 trials, also published in The Lancet, gave new insight into Novo Nordisk’s once-weekly cagrilintide-semaglutide combination, branded Cagrisema.
The REIMAGINE 1 trial [link here] enrolled patients recently diagnosed with type 2 diabetes. Those given a 2.4mg or 1mg dose of Cagrisema had greater reductions in HbA1c than those on placebo after 40 weeks. Patients then stopped treatment for 12 weeks, after which more of those who had been on Cagrisema were in diabetes remission and had improved beta-cell function than those who had been on placebo, lead author Dr Vanita Aroda, an endocrinologist at Brigham and Women’s Hospital, told a briefing at the meeting.
The REIMAGINE 2 trial compared Cagrisema with semaglutide alone and with placebo in patients also taking metformin. The 2.4mg dose of Cagrisema produced greater reductions in HbA1c than semaglutide alone, regardless of whether patients were also on an SGLT2 inhibitor.
In a Lancet commentary, Professor Andre Scheen, an endocrinologist at the University of Liège, said the results pointed to a possible “complementary action” between cagrilintide and semaglutide. He said a future head-to-head comparison with the dual agonist tirzepatide would be of major interest.
AstraZeneca’s oral GLP-1 candidate shows early promise
AstraZeneca also presented phase 2b results for its experimental oral drug elecoglipron, also known as AZD5004.
In the SOLSTICE trial, patients with type 2 diabetes who received the highest dose had their blood glucose reduced by 1.9% over 26 weeks, compared with 0.2% in the placebo group. Lead author Dr Aroda said the findings suggested small-molecule oral GLP-1 receptor agonists could offer a useful new treatment option for people with type 2 diabetes and related metabolic conditions.
In the separate VISTA trial, adults with obesity and at least one other health condition who took a 75mg dose of elecoglipron lost 11.8% of their body weight by 36 weeks, compared with 0.3% in the placebo group.
The meeting also featured new data on Lilly’s experimental triple agonist retatrutide, which cut weight by 15% in patients with type 2 diabetes — see our earlier coverage for details.