Glycemic Velocity and Early Retinal Microvascular Change With GLP-1RA Versus SGLT2i Initiation in Type 2 Diabetes (GLIDE)

NCT07723820 | Not Yet Recruiting

• 1 other identifier: MTU-EC-CE-0-208/69
• Study Type: observational
• Target: 126
• Locations: 1 country
• Sites: 1

Brief Summary

The GLIDE study looks at how the small blood vessels of the eye respond during the first months of a new diabetes medicine. Two widely used classes of glucose-lowering drugs, GLP-1 receptor agonists and SGLT2 inhibitors, are compared in adults with type 2 diabetes who have no diabetic retinopathy or only early (mild) diabetic retinopathy. When blood sugar (HbA1c) falls quickly after starting treatment, the retina can undergo a brief, temporary worsening before it stabilizes and benefits over the long term. This study asks whether it is the speed of that blood-sugar reduction, which we call "glycemic velocity," rather than the specific drug, that drives early changes in retinal and choroidal blood flow. Participants are patients whose own physician has decided, independently of the study, to start one of these two drugs for the first time. The study does not choose, provide, or change any medicine; it adds only eye imaging, blood tests, and observation. Each participant is followed with specialized, non-invasive eye scans, optical coherence tomography angiography (OCT-A) and structural/choroidal OCT, together with HbA1c and other measurements, at the start of treatment and again over the following months. The main measurement is the change, from the start of treatment to month 3, in the density of the tiny deep-layer capillaries at the center of the retina, measured on OCT-A. The study will test whether faster HbA1c reduction is linked to greater early change in these vessels and, using statistical mediation analysis, will estimate how much of any difference between the two drug groups is explained by glycemic velocity versus a direct drug effect. If glycemic velocity, a factor physicians can influence by adjusting how quickly treatment is intensified, turns out to drive early retinal change, the findings could guide safer treatment strategies and help identify patients who need closer eye monitoring when starting these medicines.

Conditions

Type 2 Diabetes Mellitus; Diabetic Retinopathy (DR)

Keywords

glycemic velocity; GLP-1 receptor agonist; SGLT2 inhibitor; OCT angiography; deep capillary plexus; retinal vessel density; foveal avascular zone; choroidal vascularity index; diabetic retinopathy; early worsening diabetic retinopathy; new-user active-comparator; causal mediation; retinal perfusion

Outcome Measures

Primary Outcomes (1)

• Change in parafoveal deep-capillary-plexus (DCP) vessel density on OCT angiography

  Vessel density (%) of the deep capillary plexus in the parafoveal ring on OCT angiography (fixed macular scan, validated quantification, pre-specified image-quality threshold, masked grading); primary metric is the change from baseline to Month 3.

  Baseline to Month 3

Secondary Outcomes (8)

• Superficial capillary plexus (SCP) vessel density and perfusion density

  Baseline to Month 3

• Foveal avascular zone (FAZ) area

  Baseline to Month 3

• Subfoveal choroidal thickness

  Baseline to Month 3

• Choroidal vascularity index (CVI)

  Baseline to Month 3

• Central subfield thickness

  Baseline to Month 3

Study Arms (2)

GLP-1 receptor agonist initiators

Adults with type 2 diabetes and no-to-mild NPDR who are starting a first-ever GLP-1 receptor agonist, prescribed by the treating physician independently of the study. Followed with the standardized multimodal retinal-imaging and metabolic battery. Primary exposure of interest, glycemic velocity, is measured within this cohort.

Drug: GLP-1 Receptor Agonists

SGLT2 inhibitor initiators

Adults with type 2 diabetes and no-to-mild NPDR who are starting a first-ever SGLT2 inhibitor, prescribed by the treating physician independently of the study. Active comparator that shares the glucose-lowering indication but is not classically associated with early retinopathy worsening. Followed with the identical battery.

Drug: SGLT2 inhibitor

Interventions

GLP-1 Receptor Agonists DRUG

First-ever GLP-1 receptor agonist initiated as routine clinical care; class and rate of titration are recorded but not controlled by the study. Mapped to Cohort 1.

GLP-1 receptor agonist initiators

SGLT2 inhibitor DRUG

First-ever SGLT2 inhibitor initiated as routine clinical care; recorded but not controlled by the study. Mapped to Cohort 2.

SGLT2 inhibitor initiators

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Adults with type 2 diabetes attending the diabetes/endocrinology clinics of Thammasat University Hospital who are initiating, for the first time, a GLP-1 receptor agonist or an SGLT2 inhibitor on their treating physician's decision, and who have no diabetic retinopathy or only mild non-proliferative diabetic retinopathy at baseline.

You may qualify if:

• Adults aged 18 years or older with a documented diagnosis of type 2 diabetes mellitus.
• Clinical decision, made by the treating physician independently of the study, to initiate a first-ever GLP-1 receptor agonist or a first-ever SGLT2 inhibitor.
• Baseline retinal status ranging from no diabetic retinopathy to mild non-proliferative diabetic retinopathy (NPDR) in the study eye(s), confirmed by fundus photography / ETDRS grading.
• Baseline HbA1c within a range permitting a measurable subsequent change (e.g., 7.0% or higher), obtained within 30 days before or after the scheduled ophthalmic assessment.
• Media sufficiently clear and fixation adequate to obtain gradable OCT-A and OCT images.
• Able and willing to provide written informed consent and to attend scheduled follow-up visits.

You may not qualify if:

• Moderate-to-severe NPDR, proliferative diabetic retinopathy, or center-involving diabetic macular edema at baseline.
• Prior or concurrent treatment for diabetic retinopathy or maculopathy: pan-retinal or focal/grid laser photocoagulation, intravitreal anti-VEGF or corticosteroid therapy, or vitreoretinal surgery.
• Any prior exposure to a GLP-1 receptor agonist or SGLT2 inhibitor (to preserve the new-user design).
• Type 1 diabetes, latent autoimmune diabetes of adults, or secondary diabetes.
• Other retinal or choroidal disease that would confound microvascular/choroidal measurement: age-related macular degeneration, retinal vein or artery occlusion, uveitis, high myopia (spherical equivalent more negative than -6.0 D or axial length greater than 26.0 mm), or significant media opacity precluding imaging.
• Coexisting glaucoma or optic neuropathy that independently alters retinal vascular or neural metrics.
• Recent (within 3 months) intraocular surgery in the study eye, including cataract surgery.
• Uncontrolled systemic hypertension or a known systemic condition (e.g., significant anemia, severe renal impairment with eGFR \< 30 mL/min/1.73 m², or active malignancy) that independently affects retinal perfusion or oximetry, at investigator discretion.
• Pregnancy, or planned simultaneous initiation of insulin such that the index glucose-lowering exposure cannot be attributed (concurrent stable insulin is permitted and recorded as a pre-specified effect modifier).
• Inability to provide informed consent or to comply with the imaging and follow-up schedule.

Sponsors & Collaborators

• Thammasart University Hospital: lead
• Thammasat University Hospital: collaborator
• Thammasat University: collaborator

Study Sites (1)

Faculty of Medicine, Thammasat University

Pathum Thani, Khlong Luang, 12120, Thailand

Location

Related Publications (7)

• von Elm E, Altman DG, Egger M, Pocock SJ, Gotzsche PC, Vandenbroucke JP; STROBE Initiative. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. Lancet. 2007 Oct 20;370(9596):1453-7. doi: 10.1016/S0140-6736(07)61602-X.

  PMID: 18064739 BACKGROUND

• Eleftheriadou A, Riley D, Zhao SS, Austin P, Hernandez G, Lip GYH, Jackson TL, Wilding JPH, Alam U. Risk of diabetic retinopathy and diabetic macular oedema with sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide 1 receptor agonists in type 2 diabetes: a real-world data study from a global federated database. Diabetologia. 2024 Jul;67(7):1271-1282. doi: 10.1007/s00125-024-06132-5. Epub 2024 Apr 8.

  PMID: 38584180 BACKGROUND

• Kapoor I, Sarvepalli SM, D'Alessio D, Grewal DS, Hadziahmetovic M. GLP-1 receptor agonists and diabetic retinopathy: A meta-analysis of randomized clinical trials. Surv Ophthalmol. 2023 Nov-Dec;68(6):1071-1083. doi: 10.1016/j.survophthal.2023.07.002. Epub 2023 Jul 16.

  PMID: 37454782 BACKGROUND

• Early worsening of diabetic retinopathy in the Diabetes Control and Complications Trial. Arch Ophthalmol. 1998 Jul;116(7):874-86. doi: 10.1001/archopht.116.7.874.

  PMID: 9682700 BACKGROUND

• Bain SC, Klufas MA, Ho A, Matthews DR. Worsening of diabetic retinopathy with rapid improvement in systemic glucose control: A review. Diabetes Obes Metab. 2019 Mar;21(3):454-466. doi: 10.1111/dom.13538. Epub 2018 Oct 15.

  PMID: 30226298 BACKGROUND

• Marso SP, Bain SC, Consoli A, Eliaschewitz FG, Jodar E, Leiter LA, Lingvay I, Rosenstock J, Seufert J, Warren ML, Woo V, Hansen O, Holst AG, Pettersson J, Vilsboll T; SUSTAIN-6 Investigators. Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes. N Engl J Med. 2016 Nov 10;375(19):1834-1844. doi: 10.1056/NEJMoa1607141. Epub 2016 Sep 15.

  PMID: 27633186 BACKGROUND

• Luo Y, Xia Y, Gong X, Hao M, Wei Q, Liao L. GLP-1 receptor agonists in eye disease: a comprehensive review of current research and future potential. BMC Ophthalmol. 2026 Jan 8;26(1):12. doi: 10.1186/s12886-025-04559-x.

  PMID: 41501669 BACKGROUND

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Diabetic Retinopathy

Interventions

Glucagon-Like Peptide-1 Receptor Agonists; Sodium-Glucose Transporter 2 Inhibitors

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Retinal Diseases; Eye Diseases; Diabetic Angiopathies; Vascular Diseases; Cardiovascular Diseases; Diabetes Complications

Intervention Hierarchy (Ancestors)

Hypoglycemic Agents; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses; Molecular Mechanisms of Pharmacological Action

Study Officials

• Kanokporn Sanpawithayakul, MD, MSc, PhD

  Department of Clinical Epidemiology, Faculty of Medicine, Thammasat University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Wit Tharanon, Doctor of medicine

CONTACT

+66944989500; wthara@tu.ac.th

Kanokporn Sanpawithayakul, MD, MSc, PhD

CONTACT

+66 86 772 4409; kanokpor2@tu.ac.th

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 3 Months
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Research fellow in Ophthalmology, Faculty of medicine, Thammasat University

Study Record Dates

• First Submitted: July 19, 2026
• First Posted: July 23, 2026
• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): September 1, 2027
• Last Updated: July 24, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

TH (1)