Semaglutide benefits held up for 3 years

Once weekly treatment with the glucagon-like peptide 1 receptor agonist (GLP-1 RA) semaglutide significantly reduced HbA_1c level and body weight in a large cohort of adults with type 2 diabetes (T2D) in a real-world study from Israel.

Semaglutide led to reductions in both HbA_1c (-0.77 percent; p<0.001) and body weight (-4.7 kg; p<0.001) up to 3 years in patients who adhered to the therapy.

“There was a clinically relevant improvement in blood sugar and significant weight loss at 6 months of treatment that was comparable with what we’ve seen in randomized trials,” said study author Dr Avraham Karasik from the Institute of Research and Innovation at Maccabi Health Services in Tel Aviv, Israel, who presented the findings at EASD 2023. “This supports the role of semaglutide in the long-term management of T2D.”

Many takers, not without questions

Karasik shared that there are many takers of once weekly semaglutide in Israel and that allowed for a larger sample size in the study. “It is a popular drug and there were questions about its long-term effect.”

Previous studies of semaglutide had a short follow-up, said Karasik. “It was interesting to see the durability of responses in the long term and what actually happened when patients discontinued the treatment.”

“It did not surprise us that those who had a higher proportion of days covered [PDC] had a better response. If you don’t take semaglutide, it doesn’t work,” he added.

The study included 23,442 patients; 6,049 of whom were followed up for ≥2 years. Mean baseline HbA_1c was 7.6–7.9 percent and BMI was 33.7. Majority of the patients were on metformin, a GLP-1 RA, or insulin, prior to taking semaglutide. [EASD 2023, abstract SO48-666]

Participants should have had redeemed at least one prescription for subcutaneous semaglutide (0.25, 0.5, or 1 mg), and had one HbA_1c measurement a year prior and at 6 months after commencing semaglutide.

The primary endpoint was change in HbA_1c from baseline to the end of follow-up. Key secondary endpoints included change in body weight from baseline to 36 months, change in HbA_1c and body weight in subgroups of patients who were persistently on therapy, and change in HbA_1c and body weight in subgroups stratified by baseline characteristics. Exploratory outcome was change in HbA_1c and weight after treatment cessation. Median follow-up in the total population was 17.6 months and 29.9 months in those who persisted with therapy for ≥2 years.

HbA_1c reduction, weight loss

After 6 months, HbA_1c was reduced by a mean of 0.77 percent (from 7.6 percent to 6.8 percent) whereas weight loss was 4.7 kg (from 94.1 kg to 89.7 kg). The reductions held up for 3 years in about 1,000 patients.

Seventy-five percent of the cohort adhered to once weekly semaglutide (PDC over 60 percent) within the first 6 months. In patients who used semaglutide for 2 years, those with high adherence (PDC of at least 80 percent) had an HbA_1c reduction of 0.76 percent after 24 months and 0.43 percent after 36 months. Reduction in body weight was 6 kg after 24 months and 5.8 kg after 36 months.

In patients with PDC below 60 percent, reductions in HbA_1c and weight were less than those with PDC of 60 percent and higher (difference of p<0.05 between groups for both outcomes).

Interestingly, some patients who discontinued semaglutide did not regain weight immediately, but this potential residual effect merits further investigation. “As for long-term outcomes, semaglutide effect did not fade out with time, and this was another encouraging point,” said Karasik.