MILAN — About 30% of people with type 2 diabetes (T2D) who started an SGLT2 inhibitor discontinued treatment within a year, and fewer than one third of those who stopped restarted treatment during the following year, a nationwide Danish study showed.

Younger age, female sex, lower income, absence of cardiorenal disease, and intercurrent clinical events were among the factors associated with discontinuation.

Three out of 10 “is quite a lot,” said lead investigator Reimar W. Thomsen, MD, PhD, of Aarhus University and Aarhus University Hospital in Aarhus, Denmark, who reported the results here at the European Association for the Study of Diabetes (EASD) 2026 Annual Meeting.

“It’s important to know what fraction of patients who start SGLT2 inhibitors in real-life clinical practice actually stop early,” he said, noting that, in randomized trials, patients receive close follow-up and encouragement to remain on treatment.

“In real life, not so much,” he added.

But stopping was not necessarily permanent, said Thomsen, describing these patterns of stopping and restarting as “dynamic treatment trajectories,” highlighting the potential to identify patients who may benefit from additional support to remain on, or resume, treatment.

Who Stops SGLT2 Inhibitors?

Using nationwide Danish registries, investigators identified 126,188 adults with T2D who initiated SGLT2 inhibitor therapy between 2016 and 2023. The median age was 65 years, 63% were men, and SGLT2 inhibitor use increased substantially during the study period.

The study comprised three linked analyses: one looked at rates of discontinuation in the whole cohort, another looked at clinical events preceding discontinuation (in 97% of those who discontinued), and the third looked at subsequent reinitiation for all patients who discontinued. For the first analysis, all initiators were followed for 1 year, with discontinuation defined as a gap of at least 90 days after the estimated end of prescription coverage.

Overall, 30.1% discontinued within 1 year (95% CI, 29.8%-30.3%). Younger people were particularly likely to stop, with discontinuation occurring in 36.1% (95% CI, 35.4%-36.9%) of those aged 50 years or younger compared with 29.1% (95% CI, 28.8%-29.5%) of those aged 51-70 years and 29.3% (95% CI, 28.9%-29.8%) of those older than 70 years. Women were also more likely to stop than men.

So “we can see some signals,” Thomsen said, suggesting that this pattern could point toward the impact of urogenital adverse events, particularly genital infections, which can substantially affect patients’ everyday lives.

The age finding was particularly interesting, he noted, because clinicians may be more cautious about initiating SGLT2 inhibitors in frail older people owing to concerns about dehydration, ketoacidosis, and acute intercurrent illness. Yet once treatment was started, younger patients were more likely to discontinue.

The study also identified a socioeconomic gradient. Discontinuation occurred in 35.2% (95% CI, 34.6%-35.8%) of people in the low-income group compared with 26.3% (95% CI, 25.8%-26.9%) in the high-income group. Thomsen said differences according to educational level were considerably smaller.

“I found it interesting that there’s some social inequality here,” Thomsen said. “Clearly more people are stopping in the low-income group than high.” Although prescription medicines are heavily subsidized in Denmark, he noted that patients still make some copayments, which could potentially contribute to the association.

Conversely, people with established cardiorenal disease were less likely to discontinue treatment. Within 1 year, 26.5% (95% CI, 25.6%-27.3%) of those with hospital-diagnosed nephropathy and 22.9% (95% CI, 22.1%-23.6%) of those with hospital-diagnosed heart failure had stopped treatment.

Thomsen suggested that clinicians may be particularly motivated to maintain SGLT2 inhibitor treatment in patients with heart or kidney disease because of the established cardiovascular and renal benefits of the drug class in these populations.

Acute Illness May Trigger Discontinuation

To investigate events that might trigger stopping treatment, the researchers conducted a nested case-control analysis involving 36,935 discontinuers, each matched by age, sex, treatment duration, and calendar year to a patient who remained on treatment. Clinical events during the 180 days before discontinuation or matching were examined.

Several acute events were strongly associated with discontinuation, although serious events were uncommon in absolute terms. Hospitalization for dehydration was associated with more than twice the odds of stopping treatment (odds ratio [OR], 2.42; 95% CI, 1.84-3.19), as was sepsis (OR, 2.41; 95% CI, 1.95-2.98). Urinary tract infection (UTI) was associated with greater odds of discontinuation (OR, 1.60; 95% CI, 1.52-1.70), while urinary stones or obstruction were associated with an OR of 1.97 (95% CI, 1.61-2.40).

Thomsen stressed an important distinction between UTIs and genital fungal infections — SGLT2 inhibitors are known to increase the risk for genital mycotic infections, he said, but evidence does not show the same underlying increase in risk for UTIs, although many clinicians believe they do.

This raises the possibility that a UTI occurring after treatment initiation may sometimes be attributed to the SGLT2 inhibitor even when the drug was not responsible, he told Medscape Medical News.

“My hypothesis is that if you get one of these UTIs, you or your doctor may ascribe it to the SGLT2 inhibitor, but you might have also gotten it without,” Thomsen said.

Preparing Patients Could Help Persistence

Thomsen said the findings point toward an opportunity to better prepare patients for possible adverse effects when treatment is initiated rather than abandoning therapy after a single event.

“You need to prepare patients for these possible side effects,” he said. This could include discussing the risk for genital fungal infections and how they can be managed, as well as the importance of maintaining adequate hydration.

“You should not stop the drug just based on one case of infection,” said Thomsen. “Sadly, that’s what we see often happens. Just one infection and then people stop. And it may not even be caused by the drug.”

He emphasized that the serious acute events identified in the registry analysis were relatively rare and therefore unlikely to account for most discontinuation.

Only 3 in 10 Restart

The investigators next followed the 37,928 people who had discontinued treatment for up to another year. Only 29.8% (95% CI, 29.4%-30.3%) reinitiated an SGLT2 inhibitor during that period.

Younger age was associated with a greater likelihood of restarting treatment (age- and sex-adjusted rate ratios [RR], 1.50; 95% CI, 1.42-1.59 for age ≤ 50 vs > 70 years), as were poor glycemic control (RR, 1.25; 95% CI, 1.16-1.35 for A1c ≥ 7.5% vs < 6.5%), reduced kidney function (RR, 1.61; 95% CI, 0.89-2.93 for estimated glomerular filtration rate < 30 vs ≥ 90 mL/min/1.73 m²), and lower socioeconomic status (RR, 1.32; 95% CI, 1.25-1.40 for low vs high income).

Women, however, were less likely to restart than men (RR, 0.81; 95% CI, 0.78-0.84).

“For females, they are more likely to stop these drugs [and] they are less likely to restart,” Thomsen said during the presentation. “There’s something going on with women and SGLT2s here that we should think about.”

The finding that almost one third of discontinuers subsequently restarted also suggests that SGLT2 inhibitor use is not necessarily a simple binary of persistent use or permanent discontinuation, Thomsen noted. Identifying patients at risk for “dynamic treatment trajectories” could enable targeted support to improve persistence.

Overall, the clinical message is that identifying patients at greater risk of stopping treatment and supporting them from the outset could help improve persistence, he said. “We should probably be better at supporting our patients. Maybe we can think about this from the beginning, if there’s some characteristic that will predict a higher risk.”

‘Troublesome’ Effects Matter to Patients

Session co-moderator Claudio Scafoglio, MD, PhD, associate professor in the Department of Medicine, Pulmonary and Critical Care at the University of California, Los Angeles, said the findings highlighted the difference between adverse effects that may appear relatively minor medically and their impact on patients’ everyday lives.

“When I read about [SGLT2 inhibitors], it says these are very safe medications; they have very mild side effects,” Scafoglio told Medscape Medical News in an interview. “And then it turns out that there is a lot of discontinuation because of urogenital infections, especially in women.”

Urogenital infections may be “very trivial from a medical point of view but can be very, very troublesome for people who actually have them,” Scafoglio pointed out. “This is something that when we design studies in the lab, we don’t think about enough.”

The findings raise the question of whether preventive measures could improve persistence, he added.

Also commenting on the findings, Søren Tang Knudsen, MD, PhD, chief physician and associate professor at Steno Diabetes Center Aarhus in Aarhus, said maintaining long-term treatment can be particularly challenging for chronic diseases that patients may not experience as symptomatic.

“The struggle is real,” he said, noting that patients may be more likely to discontinue medication if they experience, or suspect, side effects that affect their everyday lives. He said the higher discontinuation among patients with urogenital infections, particularly younger women, was therefore unsurprising.

Important for Patients With Cardiorenal Disease

Knudsen also highlighted the lower risk for discontinuation among patients with cardiorenal disease as a more encouraging finding.

These patients have particularly strong indications for SGLT2 inhibitor therapy, he said, and may be more likely to continue treatment because of advice from healthcare professionals and awareness of serious complications, including heart failure hospitalization, kidney failure, and dialysis.

“A 30% discontinuation rate is concerning given the well-established cardiorenal benefits of SGLT2 inhibitors,” added Thomas Bastholm Olesen, PhD, senior researcher at Steno Diabetes Center Odense in Odense, Denmark. “Together with Hodman Hassan’s study presented in the same session, showing that 42% of Danish patients with T2D and CKD [chronic kidney disease] did not initiate SGLT2 inhibitor treatment, it highlights challenges both in initiating and maintaining guideline-recommended therapy.”

“Better counselling about genital infections, and early recognition and treatment may help avoid unnecessary discontinuation, particularly among women,” he added.

The study was supported and funded by Boehringer Ingelheim. Thomsen reported that his department received research funding from several companies and that he gave occasional presentations and lectures on medical research for pharmaceutical companies, including AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Novo Nordisk, and Sanofi. Scafoglio reported having no relevant financial relationships. Knudsen reported having interactions with several manufacturers of SGLT2 inhibitors, including lectures and advisory board participation. Olesen reported receiving advisory board fees from AstraZeneca and an unrestricted research grant from Novo Nordisk.