June 4, 2023

Ildiko Lingvay discusses the STEP 2 findings, and why a higher semaglutide dose may be optimal for most people with type 2 diabetes.

I think the the biggest benefit is having a substantial weight loss of 10 percent in a population that it’s notoriously hard to help with weight loss and achieving that on top of improvements in other comorbidities like lowering blood sugar lowering blood pressure cholesterol and improving the cardiovascular risk factors that we know about like crp for example and

Also while improving the quality of life so that for me it’s sort of the the drug that hits it all and helps patients not from just one standpoint but from from a holistic standpoint so you had a weight loss of approximately nine point six percent and then in um in step one it was more like 15 is there a particular reason why it’s less in your trial absolutely

Yes so patients with diabetes have a much much harder time losing weight well we don’t fully understand why that is that there’s some potential explanations what that it has to do with what other medications they’re on to treat diabetes it might have to do with how much glucose they’re excreting and then when they stop excreting that because their blood sugar

Gets better all those calories are retained there are many potential explanations for that and not one good one but bottom line patients with diabetes have a very hard time losing weight on the opposite side they very much need to lose weight because uh with weight loss we know that their diabetes improves their other comorbidities improve so weight loss for

Patients with diabetes is really the quintessential intervention for their overall health so a 10 weight loss in this population is actually fantastic it’s twice as much as any other medication that is approved for obesity has done in clinical trials and while it it in absolute numbers doesn’t seem as high as step one or step three which enrolled only patients

Without diabetes in the context of diabetes this is a phenomenal result assuming the higher dose of stomachache got approved when would you use a higher dose and when would you prefer to use the lower dose in people with diabetes so um it’s an interesting conversation and it’s something that actually i’m trying to fight at a more conceptual level because for

Reasons that i think are not very physiologic but more have to do with the regulatory and cost and how issues companies cover this dichotomy between between on diabetes those and obesity dose is now present in in the previous drug which is little glutathione is gonna be present for this drug as well and potentially in others in the future and it’s really a

Very um artifactual uh differentiation right between the two dosages because our patients with diabetes like you said most of them have obesity and they would benefit from the higher dose from a weight loss perspective but i’ll tell you sort of the background and how this happened to be and that’s because uh for this medication and it seems like for the class

In general there’s a different dose response curve for glucose versus weight so what i mean by that as the dose goes up the effect on blood sugar goes up but at some point just like with the effect of any drug this plateaus or it becomes a smaller increment for a continuous increase in the dose so the optimal dose for blood sugar lowering it was found to be

Somewhere there in the 0.5 to 1 which means at that those most patients get the desired reduction in glycemia that you’re looking for but what’s been noticed is that the those response curve for weight loss it’s offset and as you keep going up on the dose they might not get a whole lot more improvement on glucose they still get an improvement on glucose but

Not incrementally that big they do get significant increment on the weight part so that’s why that’s how we ended up with these different dosages for different indications even though like you said it’s for the same patients so a dose of 2.4 was found to be optimal for weight loss um like it it provides the best uh benefit for the dose well for the glucose 0.5

To 1. dose that it’s it’s sort of the optimal point for most patients now that being said coming back to my patients with diabetes um my goal is to um when i treat patients with diabetes i like to not only treat their blood sugar which is sort of the consequence of that disease but look at the patient more holistically and see why did they get diabetes to begin

With and in most of the cases that will be because of the weight and the weight causes the diabetes and many other comorbidities that we have therefore in at least in my practice and in my view we should focus more on weight management in diabetes and that will take care of both blood sugar weight and other comorbidities and we shouldn’t just strictly focus on

Blood sugar which we know it’s good it lowers microvascular complications but it’s even better when you’re actually focusing on the root cause of the problem so could you foresee the higher dose being most most frequently used in people with diabetes i would definitely hope so as i said the challenges that could be more logistical with the insurance companies

Oftentimes not wanting to cover for obesity treatment very counterintuitive but unfortunately is the reality um and that would be a limiting factor potentially but you know in an eutopic world where you can treat patients the way you think it’s right then yes i would i would go for the full dose to three to throw because of the problem and um do you get a dose

Response for the gastrointestinal side effects as well so interestingly not that much so with a higher dose there is slightly more gastrointestinal side effects but it was way less than i expected uh most people if they have problems they i have what i’ve noticed is that they tend to have problems when they start or upon the first titration and most people if

They don’t have problems in the beginning they tend to tolerate it quite well as the dose continues to increase um so there’s not necessarily a dose response but if it is it’s very minimal to the point that it won’t change how i treat i do feel having having had a lot of experience with these drugs now i do feel that preparing the patient adequately and informing

Them of what they need to do and what they might expect mitigating any side effects early goes a long way and in most cases it’s very well tolerated and as you saw very few patients actually stop because of the gastrointestinal side effects

Transcribed from video
STEP 2: A higher semaglutide dose in people with type 2 diabetes | Ildiko Lingvay By Medicine Matters diabetes