Hi today, i’m going to discuss dual incretin therapy. This type of therapy is really the most exciting new therapy in the treatment of type 2 diabetes and we’ve had top line results from some of the clinical trials that have been performed. But we’re going to learn a lot more at the upcoming ada meetings, when the full trial results will be reported. So, first of all a little background, so we’ve had glp-1 receptor agonists around for a while now and we all know how they work and we’re pretty familiar with them. When it comes to gip.
It seemed to me that, at least in trials where they just looked at gip alone, that there wasn’t a great benefit, but it turns out that when you combine the two, when you make an agent that is synergistic and is both gip and a glp-1 receptor, agonist Called a twin incretin that you now begin to have incredible benefits, much more a1c reduction and weight loss than we saw with glp1 receptor antagonism alone.
This new medication is called Tirzepatide and is a novel, gip, glp-1, receptor agonist, and it’s based on the native gip sequence. That’s then been modified. The initial phase II trials showed significant a1c and weight loss benefits. It’s a once weekly injection and it did have gi side effects at that point fairly similar to those that we see with glp1 receptor agonist.
But i’m going to talk about that more in a minute, so the studies that have been done are called the surpass clinical trials, and this is a huge, clinical trial program. Frankly, because this is a new class of drugs, they’ve enrolled more than 13 000 participants with type 2 diabetes around the globe and, I believe, there’s ten clinical trials. Five are the pivotal trials and there’s also a cardiovascular outcome studies and they basically look at a variety of different doses. So one milligram five milligram, 10 milligram and 15 milligram and they compare it to placebo or an active comparator and they’re basically looking at everything. So, for instance, surpass one compares to zepatite to placebo, surpass two compares it to one milligram of cementite.
They compare it to insulin deglodec, they compare it to glargine, they compare it to a sglt2 inhibitor to metformin. So this is a very comprehensive approach to looking at these agent to see what it does compared to agents. We’re used to using the primary endpoint for all of these trials is the change in a1c from baseline, but there are many secondary endpoints, including change in body weight and seeing how many people achieve specific targets, as well as the impact on rates of hypoglycemia.
Dr julio rosenstock has taught me most of what I know about these agents and is going to be one of the presenters at the ADA. But he basically states that all four trials that basically have been announced and will be discussed, reported that they met their primary and secondary endpoints and that Tirzepatide showed substantially greater reductions in a1c and body weight compared to placebo and all active comparators.
So this has great potential to advance our ability to treat people with type 2 diabetes. On the other hand, I think we need to know a little bit more. I personally always want to make sure that they’re safe, that any new agent is safe for my patients, and I do know that these agents probably have more gi side effects than we see at the higher doses of the existing glp1 receptor agonist.
They seem to have a higher dropout rate in the clinical trials due to gi side effects compared to the more traditional agents. So we need to get a sense of how these drugs behave in terms of side effects. But if you look at the data that we’ve seen thus far, they’re pretty darn impressive in terms of a1c reduction and weight loss and hopefully, there’ll be another tool that we have to treat our patients with type 2 diabetes. Thank you.
Read More: Once-Weekly Tirzepatide for Obesity