Retatrutide

Retatrutide

Tilpotide is the best weight-loss drug among the GLP-1 drugs that have been developed.

In the Phase III SURMOUNT-1 study of obese subjects without type 2 diabetes, after 72 weeks of treatment with tilpotide, participants in the 15mg dose group lost an average of up to 22.5% (24 kg) of body weight;

In the Phase III SURMOUNT-2 study of obese subjects with type 2 diabetes, after 72 weeks of treatment with tilpotide, participants in the 15mg dose group lost an average of 15.7% of their body weight.

Lilly said at the time that it was the first investigational drug to achieve an average weight loss of more than 20 percent in a Phase 3 clinical trial. Because of the outstanding weight loss effect, tilpotide was sold immediately. Although the growth rate of the latest three quarters was less than market expectations, total sales of tilpotide still reached $4.37 billion, and the total amount of the first three quarters was as high as $11 billion, narrowing the gap with Novo Nord Semaglutide again.

In Lilly’s latest projections, Retatrutide will outperform Tipotide.

Under the condition of safety and tolerability, the highest dose of the drug at 48 weeks can reduce weight by 22% to 24%, while reducing the glycated hemoglobin (HbA1c) by 2% in diabetic patients at 36 weeks.

Lilly last year published a Phase II study of Retatrutide weight loss. The results showed that participants in the 12mg Retatrutide group lost 17.5 percent of their body weight after 24 weeks of treatment, which reached 24.2 percent at 48 weeks. And from the weight loss curve, it has not reached a plateau. Another Phase II trial involving patients with type 2 diabetes showed a 2.02% reduction in HbA1 at 24 weeks in the 12mg dose group (0.01% in the placebo group).

If it can maintain this effect, Lilly is not too excited about Retatrutide, and it is only a matter of time before Tipotide becomes a head-to-head competitor.

The key reason why Retatrutide can show stronger potential than tilpotide lies in its mechanism. Retatrutide is currently the fastest glucose-reducing and weight-reducing drug targeting GLP-1R/GIPR/GCGR. It adds a GCG on the basis of the single target GLP-1 and double target GLP-1/GIP used in the past.

All three are hormones closely related to blood sugar levels. GLP-1 and GIP are secretins that promote insulin secretion, induce satiety and reduce appetite, while GCG can induce energy expenditure and increase lipid metabolism.

Previous studies have found that combining GLP-1 signaling with GIP, GCG, or both can enhance insulin responses beyond those produced by GLP-1 alone. Telpotide has shown strong competitiveness in the GLP-1R/GIPR dual target, and Retatrutide builds on it by activating GCGR to increase energy expenditure, thereby achieving glycemic control and weight loss beyond the dual target.

Based on confidence in the mechanism and validation of past clinical data, Lilly is accelerating the clinical development of Retatrutide. Previously, Lilly had initiated eight Phase 3 trials for Retatrutide, including five for weight loss and three for type 2 diabetes. Among them, the number of patients with weight loss indications was more than 5,000.

Although telpotide’s weight-loss indication was just approved in November last year, it is gaining momentum. But, for Lilly, it was more of a head-to-head experiment that had to be done. From GLP-1 single target to dual-target weight loss drugs, GLP-1 combined therapy, there are countless entrants, and no one is willing to miss this potential market.

It’s better to iterate than to be subverted by others.