medwireNews: The response to glucagon-like peptide (GLP)-1 receptor agonists varies widely among people with type 2 diabetes but more than half achieve a meaningful reduction in either bodyweight, glycated hemoglobin (HbA1c), or both, show real-world data from the IMI-SOPHIA study.
Martin Heni (Ulm University, Germany) and co-authors say the “data provide some insights into factors influencing treatment response, but developing robust biomarkers may be necessary for precision medicine approaches at the individual level.”
They report in Diabetologia that, after 6 months of treatment with liraglutide, semaglutide, or dulaglutide, the median absolute reduction in HbA1c reduction was 0.5 percentage points (5.3 mmol/mol) among 4467 adults (median age 60 years, 45% women) with type 2 diabetes from the Diabetes Patient Follow-up registry. The median relative bodyweight reduction was 1.43%.
At baseline, their median HbA1c was 7.7% (60 mmol/mol) and their median BMI was 34.9 kg/m2.
Overall, 14.0% of participants achieved clinically meaningful improvements in both HbA1c and bodyweight, defined as an absolute reduction of at least 0.5% (5.5 mmol/mol) and a relative reduction of at least 5.0%, respectively.
Heni et al note that this proportion “was lower than in clinical trials, which often involve highly selected, motivated populations that might therefore not be representative of the wide spectrum of individuals with type 2 diabetes in routine clinical practice.”
A further 35.7% achieved a meaningful reduction in HbA1c only and 7.4% had a meaningful weight reduction only, with the remaining 42.9% showing no significant reduction in either measure.
Further analysis revealed that men were significantly more likely than women to be in the only HbA1c responder group than in the HbA1c and weight responder group, at an odds ratio (OR) of 1.53.
Individuals with an elevated baseline HbA1c were also significantly more likely to have an HbA1c only response (OR=1.13 per 10 mmol/mol increase) whereas those with a higher BMI were less likely to be in the only HbA1c responder group (OR=0.87 per 10 kg/m2 increase).
The likelihood of only experiencing a meaningful weight reduction compared with an HbA1c and weight reduction increased significantly with age (OR=1.31 per 10 years) and diabetes duration (OR=1.28 per 5 years), but decreased with higher baseline HbA1c (OR=0.52 per 10 mmol/mol increase).
When the researchers analyzed the associations between baseline characteristics and overall weight or HbA1c changes across all response groups they found that higher baseline bodyweight and lower estimated glomerular filtration rate significantly correlated with greater weight reduction, whereas lower baseline HbA1c and longer diabetes duration were significantly associated with smaller HbA1c reductions.
Heni and co-authors conclude: “Although higher baseline HbA1c predictably associates with greater glycaemic reductions, the marked heterogeneity in response highlights that baseline HbA1c alone does not fully capture treatment variability.”
They add: “This underscores the importance of identifying additional clinical or biological factors that can better predict glycaemic response to GLP-1 [receptor agonist] treatment.”
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Diabetologia 2025; doi: 10.1007/s00125-025-06448-w
