(No investment advice, yadda yadda) I thought I’d give you a glimpse into a slice of the healthcare week. You may have been reading a lot about newly launched obesity drugs and I covered some of this in my podcast last year with Stephan Guyenet in anticipation.

But, the R&D does not stop with current obesity research. A US biopharma company has revealed data on what is dubbed “Triple G” - so called because it is a triple combination of a GIP, a GLP-1 and a glucagon.  

Sorry all those who gave up university science or never even went there but, in sum, 

This approach is the concurrent activation of the glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic peptide (GIP), and glucagon (Gcg) receptors (i.e. triagonism). The idea is that this combines the anorectic and insulinotropic activities of GLP-1 and GIP with the energy expenditure effect of glucagon.

There is about 50 years or more of science within that statement so don’t feel bad about not knowing. If you really want to understand more check out this journal paper in Cell.  The bottom line is that the phase II results were very striking (although need to replicated in phase 3)

The date showed that patients on the highest dose lost 22% of their bodyweight on a placebo-adjusted basis at the 48-week point.

As reported by Elizabeth Cairns of  Evaluate Pharma:

“....prompted one delegate to ask whether future obesity trials might look at getting patients out of the obese or even overweight categories altogether, bringing their body mass index down to 25 or less. The average weight loss of 58lb (26kg) seen in the trial could take a patient from a BMI of 35 to “a skinny 28”, Dr Julio Rosenstock of Velocity Clinical Research, another presenter at the symposium, said.

Dr Jastreboff had earlier pointed out that the weight reduction curve was still continuing at 48 weeks, suggesting that even greater weight loss could be produced after longer treatment. Maybe obesity resolution is not such a crazy thing to aim for.” [My emphasis, but it’s not out of reach, maybe??]

There are potential side effects though, so it’s not a complete home run yet.

That will only be a possibility, however, if patients can tolerate retatrutide. Nausea and vomiting were more of a problem with the triple G than with Wegovy and Mounjaro, and SVB analysts singled out the 7% rate of cutaneous hyperesthesia – hypersensitivity of the skin – as something requiring further investigation and management. 

They also highlighted a patient in retatrutide’s highest dose group who had prolonged QT interval, albeit a subject who was also on ondansetron for nausea, a drug that is associated with this irregular heart rhythm. Still, prolonged QT interval also occurred in the phase 2 diabetes trial of Pfizer’s oral GLP-1 danuglipron, and this is a signal that will be watched for as the incretin class outcome trials report. 

For now, the discontinuations seen with the high dose of retatrutide, all of which were due to gastrointestinal issues, are most worrisome. Dr Jastreboff said that dose escalation was still being optimised, suggesting that phase 3 trials might use a slower titration schedule. The dose for phase 3 has yet to be determined, she added.