Once weekly glucagon-like peptide 1 receptor agonist (GLP-1 RA) semaglutide (Ozempic, Novo Nordisk) significantly improved A1c level and body weight for up to 3 years in a large cohort of adults with type 2 diabetes, show real-world data from Israel.

Treatment with semaglutide was associated with reductions in both A1c (-0.77%; P < .001) and body weight (-4.7 kg; P < .001) at 6 months of treatment. These reductions were maintained for up to 3 years and, in particular, in those patients with higher adherence to the therapy.

Avraham Karasik, MD, from the Institute of Research and Innovation at Maccabi Health Services, Tel Aviv, Israel, led the study and presented the work as a poster at this year's annual meeting of the European Association for the Study of Diabetes (EASD).

"We found a clinically relevant improvement in blood sugar control and weight loss after 6 months of treatment, comparable with that seen in randomized trials", said Karasik during an interview with Medscape Medical News. "Importantly, these effects were sustained for up to 3 years, supporting the use of once weekly semaglutide for the long-term management of type 2 diabetes."

Esther Walden, RN, deputy head of care at Diabetes UK, appreciated that the real-world findings reflected those seen in the randomized controlled trials. "

- This study suggests that improvements in blood sugars and weight loss can potentially be sustained in the longer-term for adults with type 2 diabetes taking semaglutide as prescribed."

Large Scale, Long-Term and Real-World

Speaking to Medscape Medical News, Karasik explained that in Israel, there are many early adopters of once weekly semaglutide, and as such, it made for a large sample size, with a significant use duration for the retrospective study.

- "It's a popular drug and there are lots of questions about durability of effect," he pointed out.

Though evidence from randomized controlled trials support the effectiveness of once weekly semaglutide to treat type 2 diabetes, these studies are mostly of relatively short follow-up, explained Karasik, pointing out that long-term, large-scale, real-world data are needed.

- "In real life, people are acting differently to the trial setting and some adhere while others don't, so it was interesting to see the durability as well as what happens when people discontinue treatment or adhere less."

"Unsurprisingly, people who had a higher proportion of days covered ([PDC]; the total days of semaglutide use as a proportion of the total number of days followed up) had a higher effect," explained Karasik, adding that, "if you don't take it, it doesn't work."

A total of 23,442 patients were included in the study, with 6049 followed up for 2 years or more. Mean baseline A1c was 7.6%-7.9%; body mass index (BMI) was 33.7-33.8; metformin was taken by 84%-88% of participants; insulin was taken by 30%; and 31% were treated with another GLP-1 RA prior to receiving semaglutide.

For study inclusion, participants were required to have had redeemed at least one prescription for subcutaneous semaglutide (0.25, 0.5, or 1 mg), and had at least one A1c measurement 12 months before and around 6 months after the start of semaglutide.

The primary outcome was change in A1c from baseline to the end of the follow-up at 6, 12, 18 24, 30, and 36 months. Key secondary outcomes included change in body weight from baseline to the end of the follow-up (36 months); change in A1c and body weight in subgroups of patients who were persistently on therapy (at 12, 24, 36 months); and change in A1c and body weight in subgroups stratified by baseline characteristics. There was also an exploratory outcome, which was change in A1c and weight after treatment discontinuation. Karasik presented some of these results in his poster.

Median follow-up in the total population was 17.6 months and was 29.9 months in those who persisted with therapy for 2 years or more. "We have over 23,000 participants so it's a large group, and these are not selected patients so the generalizability is better."

3-Year Sustained Effect

Results from the total population showed that A1c lowered by a mean of 0.77% (from 7.6% to 6.8%) and body weight reduced by 4.7 kg (from 94.1 kg to 89.7 kg) after 6 months of treatment. These reductions were maintained during 3 years of follow-up in around 1000 patients.

A significant 75% of participants adhered to once weekly semaglutide (PDC of over 60%) within the first 6 months. In patients who used semaglutide for at least 2 years, those with high adherence (PDC of at least 80%) showed an A1c reduction of 0.76% after 24 months and of 0.43% after 36 months. Body weight was reduced by 6.0 kg after 24 months and 5.8 kg after 36 months.

Reductions in both A1c and weight were less in patients with PDC of below 60% compared with those with PDC of 60%-79% or 80% or over (statistically significant difference of P < .05 for between groups for both outcomes across maximum follow-up time).

As expected, among patients who were GLP-1 RA–naive, reductions in A1c level and body weight were more pronounced compared with GLP-1 RA–experienced patients (A1c reduction, -0.87% vs -0.54%; weight loss, -5.5kg vs -3.0 kg, respectively; P < .001 for between-groups difference for both outcomes).

Karasik reported that some patients who stopped taking semaglutide did not regain weight immediately and that this potential residual effect after treatment discontinuation merits additional investigation. "This is not like in the randomized controlled trials. I don't know how to interpret it, but that's the observation. A1c did increase a little when they stopped therapy compared to those with PDC [of 60%-79% or 80% or over] (P < .05 for between-groups difference for both outcomes in most follow-up time)."

He also highlighted that in regard to the long-term outcomes, "unlike many drugs where the effect fades out with time, here we don't see that happening. This is another encouraging point."


European Association for the Study of Diabetes (EASD). October 2-6, 2023. Presented as a poster.

From www.medscape.com



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