Lilly's amylin add-on pushes tirzepatide weight loss to 23 percent among patients who stayed on it

STAT reports the 23.3% figure for participants "who stayed on the treatment" at the top combination dose ^[7]. Against 14.8% on tirzepatide alone, that is a gap of 8.5 percentage points ^[1], or about 8.9 kg using New Scientist's averages of 24.5 kg and 15.6 kg ^[2]. The arms did not keep their participants equally ^[14]. Up to 27% of people in the combination groups dropped out, against 3% on tirzepatide alone and 17% on placebo ^[14]. At the high end, that is nine times the tirzepatide rate ^[3]. When attrition is that uneven, an on-treatment average describes the people who could tolerate the pair, and compares them with nearly everyone assigned to tirzepatide ^[7]. Neither report includes the weight loss counted across everyone randomised, including those who stopped.

Suppose the top-dose arm lost the highest dropout rate reported for any combination group, 27%, and every one of those people lost no weight at all. The arm's average would still be about 17.0% ^[6]. Treating tirzepatide's 3% dropout the same way gives about 14.4% ^[7]. Under those deliberately harsh assumptions the combination still leads, by about 2.6 points instead of 8.5 ^[8].

The placebo arm lost 3% ^[6], and randomisation against it is what lets the drugs take credit for the difference. "It's a pretty astonishing degree of weight loss," said David Preiss of the University of Oxford, who was not involved in the research ^[20]. Tirzepatide mimics two appetite-suppressing hormones, GLP-1 and GIP ^[3]. Eloralintide targets a third, amylin ^[2]. Lora Heisler of the University of Aberdeen, who was also not involved, said adding a drug that acts like amylin alongside tirzepatide effectively brings a third appetite-regulating pathway into play, and that this may explain why the combination appears to deliver substantially greater weight loss ^[9].

On blood sugar, the combination's edge over tirzepatide is small. The high-dose combination beat tirzepatide alone by half a percentage point ^[4], while tirzepatide beat placebo by 2.1 points ^[5]. "These are massive reductions [with EloraTZP]," Preiss said ^[11]. He said he would expect the changes to lower the risk of cardiovascular complications and high blood pressure, though further studies are needed ^[12].

In a clinic, the question is whether people keep taking it. Mild to moderate diarrhoea, nausea and vomiting were more common on the combination ^[13]. Preiss said those side effects are probably why so many in the combination groups dropped out ^[14]. "They might find the combination more difficult to tolerate; if the patient's already doing well on a drug like tirzepatide, then additional benefit may not outweigh the added treatment burden or side effects," Heisler said ^[15]. Preiss added that people who only need to lose a small or moderate amount of weight may not be candidates for it ^[16].

In this trial the two drugs went in as separate weekly shots ^[2]. Lilly says the larger follow-up trial will give them as one weekly injection ^[17]. Regulators would therefore judge a different formulation from the one whose side effects were measured here. If all goes smoothly, the US Food and Drug Administration could approve the approach within a few years, Heisler said ^[18]. Weight-loss drugs consistently work better in people who have obesity without diabetes, for reasons Preiss said are unclear, and he expects EloraTZP could do more in that group once trials test it ^[19]. I'd expect the next trial to be judged on how many people stay on the drug at least as much as on the average weight they lose.