Large individual variability, combination therapies on horizon
Dr. Kaplan pointed out, however, that “like [with] other antiobesity therapies ... there’s a large patient-to-patient variability.”
A third of patients exhibit more than 20% weight loss, and 10% exhibit more than 30% weight loss – approaching the efficacy of bariatric surgery.
However, nearly 10% of patients without diabetes and upwards of 30% of patients with diabetes will experience less than 5% weight loss, he said.
Therefore, “success or failure in one patient doesn’t predict response in another, and we should always remember that as we treat different patients with these medications,” Dr. Kaplan advised.
A recent phase 1b study suggests that combination therapy with semaglutide and the amylin agonist cagrilintide ups weight loss, as previously reported.
In this short trial with no lifestyle modification, it took 16 weeks for patients to reach full dosing, and at 20 weeks, patients on semaglutide had lost 8% of their initial weight, whereas those on combination therapy had lost 17% of their initial weight.
“There’s hope that, in combination with cagrilintide and probably with several other agents that are still in early development, we’ll be seeing average weight loss that is in the range of that seen with bariatric surgery,” Dr. Kushner said.
Doctors discuss two hypothetical cases
Session moderator Julio Rosenstock, MD, of the University of Texas, Dallas, a coinvestigator in several of the STEP trials, invited Dr. Kaplan and two other panelists to explain how they would manage two hypothetical patients.
Case 1
You have a patient with type 2 diabetes, a body mass index of 32, 33 kg/m2, and an A1c of 7.5% or 8% on metformin. Would you use semaglutide 1 mg (Ozempic, Novo Nordisk) that is indicated for type 2 diabetes, or would you use semaglutide 2.4 mg that is indicated for obesity and risk factors?
“We have the answer to that from STEP 2,” said Melanie J. Davies, MB ChB, MD, professor of diabetes medicine at the University of Leicester, England, who led the STEP 2 trial.
Sara Freeman/MDedge News
Dr. Melanie J. Davies
“For some patients, the 1-mg dose, which we use routinely in the clinic, may be reasonable to get good glycemic control for cardiovascular protection and will obviously achieve some weight loss. But if you really want to go for the weight-related comorbidities, then the 2.4-mg dose is what you need,” she said.
“A lot of [clinicians] might say: ‘I’ll see how [the patient goes] with the 1-mg dose, and then maybe if they’re not losing the weight and not getting to glycemic target, then maybe I’ll switch to 2.4 mg,’” said John Wilding, MD, who leads clinical research into obesity, diabetes, and endocrinology at the University of Liverpool, England, and led the STEP 1 trial.
“But the STEP 2 data show very clearly that you get almost the same A1c,” Dr. Rosenstock interjected. “I would go for 2.4 mg. The patient has a BMI of 32, 33 kg/m2. I would hit hard the BMI. We need to change that paradigm.”
“For other diseases we don’t always go to the maximum dose that’s available. We go to the dose that’s necessary to achieve the clinical endpoint that we want,” Dr. Kaplan noted. “I think one of the challenges is going to be to learn how to clinically nuance our therapy the way we do for other diseases.”
“That is the usual thinking,” Dr. Rosenstock agreed. But “with the 2.4-mg dose, one third get a 20% reduction of BMI, and 10% get almost a 30% reduction – and you [aren’t] going to see that with semaglutide 1 mg!”
“That’s true,” Dr. Kaplan conceded. However, a patient with a relatively low BMI of 32, 33 kg/m2 may not need the higher dose, unlike a patient who has a BMI of 45 kg/m2 and diabetes. But we’re going to find that out over the next couple of years, he expects.