In the latest trial results Eloralintide and Tirzepatide produced greater weightloss vs either product by themselves but a considerable amount – up to 23.3% body weight.
Weight Loss akin to Metabolic Surgery Results
Eloralintide is a once-weekly selective amylin receptor agonist, while tirzepatide is a dual GIP/GLP-1 receptor agonist. Their combination therefore targets three nutrient-stimulated hormonal pathways involved in appetite and glycemic regulation: amylin, GIP, and GLP-1.
The 48-week, randomized, double-blind, placebo-controlled trial enrolled ~360 adults with obesity or overweight and type 2 diabetes (T2D) in the US and Argentina. Participants were randomized to 10 treatment groups receiving placebo, various doses of eloralintide or tirzepatide alone, combinations of the two agents, or a sequential regimen in which eloralintide was added following tirzepatide dose escalation.
At baseline, mean body weight was 232.4 lb (105.4 kg), and mean HbA1c was 8.1%. The primary endpoint was the percentage change in body weight from baseline to week 48 with combination therapy versus placebo. Comparisons with tirzepatide and eloralintide monotherapy were secondary endpoints.
The Results
Weight loss increased with higher-dose combination regimens. At week 48, mean weight reductions were 13.2% with eloralintide 3 mg plus tirzepatide 5 mg, 19.4% with eloralintide 6 mg plus tirzepatide 5 mg, 19.9% with eloralintide 6 mg plus tirzepatide 10 mg, and 23.3% with eloralintide 9 mg plus tirzepatide 15 mg.
By comparison, mean weight loss was 14.8% with tirzepatide 15 mg alone and ranged from 8.2% to 12.3% with eloralintide monotherapy. Participants receiving placebo lost an average of 3.0% of body weight. In absolute terms, the highest-dose combination resulted in a mean weight loss of 54.1 lb, compared with 34.4 lb with tirzepatide 15 mg alone.
Billings emphasized how substantially expectations for pharmacologic weight loss have evolved in recent years. “We used to really try for 5% and 10%, and the fact that we’re starting at 15% is pretty incredible,” she said.
At higher thresholds of weight loss, 62% of participants receiving the add-on regimen of tirzepatide 15 mg plus eloralintide 3 or 6 mg achieved at least 20% weight loss by week 48. Additionally, 36% achieved at least 25% weight loss, while 19% achieved at least 30%. Across the high-dose combination regimens, as many as 25% of participants achieved at least 30% weight loss.
Billings characterized this magnitude of weight loss as “very much in line with what we might expect with metabolic surgery.”
A very promising combination, although more research is required but the outlook is very promising!