Heterogeneity in response to GLP-1 receptor agonists in type 2 diabetes in real-world clinical practice: insights from the DPV register - an IMI-SOPHIA study

Diabetologia. 2025 Aug;68(8):1666-1673. doi: 10.1007/s00125-025-06448-w. Epub 2025 May 22.

Abstract

Aims/hypothesis: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are a cornerstone in type 2 diabetes management. In this study we evaluated heterogeneity in body weight and glycaemic responses to the initiation of liraglutide, semaglutide or dulaglutide in real-world clinical practice.

Methods: Data from 4467 adults with type 2 diabetes in the Diabetes Patient Follow-up (DPV) registry were analysed, focusing on changes in HbA1c and body weight over 6 months following initiation of a GLP-1 RA. We categorised participants based on their response: HbA1c reduction only, weight loss only, both or neither. This analysis was part of the IMI-Stratification of Obesity Phenotypes to Optimize Future Obesity Therapy (IMI-SOPHIA) project.

Results: At 6 months' follow-up the median absolute HbA1c reduction was 5.3 mmol/mol (IQR 13.9, -1.0) (0.49% [1.27, -0.09]) and relative body weight reduction was 1.43% (4.26, 0). Only 14% of participants achieved meaningful reductions in both HbA1c (absolute reduction ≥5.5 mmol/mol [0.5%]) and body weight (relative reduction ≥5%). Men and those with a higher baseline HbA1c were more likely to show an HbA1c only response (36% of participants; both p<0.001), while older individuals and those with a longer diabetes duration were more likely to experience a weight-only response (7% of participants; both p<0.001). Higher baseline body weight and lower eGFR (both p<0.05) correlated with greater weight reduction, whereas lower baseline HbA1c and longer diabetes duration were linked to smaller HbA1c reductions (both p<0.001).

Conclusions/interpretation: There is significant heterogeneity in responses to GLP-1 RA therapy among individuals with type 2 diabetes in routine clinical practice. However, in our study a substantial proportion achieved a reduction in either body weight or HbA1c. Future studies should explore why some individuals achieve either weight loss or HbA1c reduction but not both.

Keywords: Body weight; GLP-1 receptor agonists; HbA1c; Heterogeneity; Real life.

MeSH terms

  • Aged
  • Blood Glucose / drug effects
  • Blood Glucose / metabolism
  • Body Weight / drug effects
  • Diabetes Mellitus, Type 2* / blood
  • Diabetes Mellitus, Type 2* / drug therapy
  • Diabetes Mellitus, Type 2* / metabolism
  • Female
  • Glucagon-Like Peptide 1
  • Glucagon-Like Peptide-1 Receptor Agonists*
  • Glucagon-Like Peptides / analogs & derivatives
  • Glucagon-Like Peptides / therapeutic use
  • Glycated Hemoglobin / metabolism
  • Humans
  • Hypoglycemic Agents* / therapeutic use
  • Immunoglobulin Fc Fragments / therapeutic use
  • Liraglutide / therapeutic use
  • Male
  • Middle Aged
  • Recombinant Fusion Proteins / therapeutic use
  • Registries
  • Semaglutide
  • Weight Loss / drug effects

Substances

  • Glucagon-Like Peptide-1 Receptor Agonists
  • Liraglutide
  • Hypoglycemic Agents
  • Glycated Hemoglobin
  • Glucagon-Like Peptides
  • Immunoglobulin Fc Fragments
  • Recombinant Fusion Proteins
  • Blood Glucose
  • Glucagon-Like Peptide 1
  • Semaglutide
  • dulaglutide
  • hemoglobin A1c protein, human