Once-weekly semaglutide for T2D good enough in real-world use

A once-weekly dosing of the glucagon-like peptide-1 receptor agonist (GLP-1RA) semaglutide for type 2 diabetes (T2D) passes muster in real world, conferring benefits for blood sugar and weight across adult patients with varying characteristics and background medication, according to the Denmark (DK)/Sweden (SE) data from the SURE programme.

The findings affirm the efficacy of semaglutide reported in the phase III SUSTAIN clinical trials, the investigators said. “While the SUSTAIN trials included [individuals] across the continuum of care, eligibility criteria in SURE DK/SE were even less restrictive, capturing a broad spectrum of adults initiating semaglutide in real-world clinical practice.”

SURE DK/SE followed for at least 30 weeks a total of 331 T2D patients (107 in DK and 224 in SE; mean age 61.1 years, 35.3 percent female, disease duration 10.5 years). Frequent reasons endorsed for initiating semaglutide were as follows: improve glycaemic control, address cardiovascular risk factors, reduce weight, and simplify treatment regimen. Most of the patients were started on a 0.25-mg dose.

At baseline, HbA1c was 7.9 percent, body weight was 101.5 kg, body mass index (BMI) was 34 kg/m², and waist circumference was 115.7 cm, with no significant differences between the DK and SE cohorts. Hypertension was the most common cardiovascular comorbidity (57.9 percent and 78.6 percent), followed by dyslipidaemia (38.3 percent and 73.7 percent).

There were 282 (85 percent) patients who completed the study on semaglutide. Over a median follow up of 34.1 weeks, HbA1c decreased by a mean of –1.2 percentage points (95 percent confidence interval [CI], –1.3 to –1.1; or –13 mmol/mol, 95 percent CI, –14 to –12; p<0.0001). On the other hand, body weight dropped by a mean of –5.4 kg (95 percent CI, –6.0 to –4.7; p<0.0001). The estimates were comparable in the two cohorts. [Prim Care Diabetes 2021;doi:10.1016/j.pcd.2021.06.008]

At the end of the study, 67.5 percent of patients attained HbA1c <7 percent, 49.4 percent lost ≥5 percent of their weight, and 34.8 percent showed both an HbA1c reduction of ≥1 percentage point and a weight loss of ≥3 percent. Moreover, 87.2 percent of the population achieved clinical success in relation to the reason semaglutide was initiated.

In terms of safety, 32 adverse events (AEs) occurred in 21 patients; 25 AEs were nonserious, among which 17 were gastrointestinal and 23 were potentially related to treatment. Five patients (1.8 percent) developed severe (n=1) or documented (n=4) hypoglycaemia, all of whom belonged in the SE cohort and using concomitant insulin.

As neighbouring countries, Denmark and Sweden have similar populations and lifestyles, the investigators noted. Although there are some disparities in T2D management and prescribing patterns for glucose-lowering drugs, such as insulin, as a result of clinical practice and regulatory conditions. [Prim Care Diabetes 2021;15:262-268]

“For example, GLP-1RAs are typically introduced earlier in the treatment cascade in Denmark vs Sweden; this may result in frequent prescription of semaglutide in patients with less severe T2D and fewer additional risk factors in Denmark but similar prescription frequencies in patients with more progressed T2D in the two countries. In this context, it may be unsurprising that patients in Sweden were more frequently on medications associated with hypoglycaemia, such as sulphonylureas and insulins, and that hypoglycaemia was more common in Sweden, both before and after semaglutide initiation,” they pointed out. [Front Endocrinol 2017;8:6]

Given that the hypoglycaemic events all occurred in patients on concomitant insulin, the investigators recommended to consider lowering the dose of any concomitant secretagogues or insulin to minimize the risk of hypoglycaemia when initiating semaglutide. [https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/209637s003lbl.pdf]

“Future real-world evidence from other countries, regions, and healthcare service models will provide additional information regarding the clinical use of [the GLP-1RA],” they added.