Combining the popular weight-loss medication tirzepatide with another hormone mimic may boost the drug’s effectiveness, according to the results of a recent clinical trial.
While the findings imply the groundbreaking medication could help more people return to a healthier level of body fat, a reported increase in uncomfortable side effects may also dissuade many from giving it a go.
In a 48-week investigation conducted by pharmaceutical giant Eli Lily, an experimental treatment called EloraTZP helped adults with obesity and type 2 diabetes lose an average of nearly a quarter of their body mass; considerably more than the 14.8% achieved with the highest dose of tirzepatide, produced and sold by Eli Lilly under the brand name Mounjaro.
The results suggest that targeting three complementary hormonal pathways offers a more powerful approach to managing obesity and blood sugar levels.
Tirzepatide already targets two distinct pathways involved in regulating metabolism: one activated by the hormone glucagon-like peptide-1 (GLP-1), the other by glucose-dependent insulinotropic polypeptide (GIP). These hormones each play a critical role in regulating our blood sugar and appetite, making them useful targets for treating obesity and type 2 diabetes.
Eloralintide is an experimental drug that mimics the effects of the hormone amylin. Naturally released by the pancreas after eating, amylin also helps regulate appetite and promotes feelings of fullness.
By combining the two medications, EloraTZP is designed to build on the effects of tirzepatide while introducing a complementary mechanism for controlling food intake.
In Eli Lily’s recent Phase 2b study, 367 adults received different doses of eloralintide, tirzepatide, their combination, or a placebo. At the highest combination dose – 9 mg of eloralintide and 15 mg of tirzepatide – participants lost an average of 23.3% of their starting body weight after 48 weeks.
By comparison, those receiving 15 mg of tirzepatide alone lost an average of 14.8%.
The combination also resulted in a greater improvement in blood glucose control. Participants on the highest dose experienced an average 2.9% drop in HbA1c, a measure of longer-term blood sugar levels. Tirzepatide alone reduced it by 2.4%.
Even lower-dose combinations showed substantial effects, with weight reductions ranging from 13.2% to 19.9%.
Adding another hormone-targeting drug wasn't without drawbacks. Gastrointestinal problems, such as nausea, were the most common adverse events, generally experienced as doses were increased. These were more frequent among people receiving the combination than those taking either drug alone.
Up to roughly a quarter of participants receiving EloraTZP discontinued treatment because of adverse events. The equivalent figure for tirzepatide alone was barely 3%. That difference could prove important. A treatment that produces greater weight loss isn't necessarily a better option if patients won’t tolerate it.
The results reflect growing interest in treatments that combine the body’s hormonal signals to reduce obesity. Amylin-based drugs are attracting particular attention because they may complement the appetite-suppressing effects of incretin-based treatments.
Eli Lilly is already investigating eloralintide as a standalone obesity treatment in additional clinical trials.
The company now plans to initiate Phase 3 testing on EloraTZP, using an optimized dose-escalation schedule in an attempt to make it more tolerable. It also plans to develop a co-formulated version, potentially allowing both drugs to be delivered in a single injection.
Significant questions remain. The current findings come from a relatively small, mid-stage trial involving people with type 2 diabetes. The results were also reported through a press release and not in a peer-reviewed publication, and would also need to be confirmed in larger studies.
For now, the findings offer another indication that the future of obesity medicine may involve more than finding a single hormone to switch on or off.
Combining several complementary signals could deliver greater benefits. Provided the body can tolerate the treatment.
Source: Eli Lilly
