Effect of SGLT2i on Diabetic Retinopathy in Type 2 Diabetes Mellitus Patients

Diabetic Retinopathy Clinical Trial

Official title:

Evaluation of the Effect of Sodium-Glucose Cotransporter-2 (SGLT2) Inhibitors on Diabetic Retinopathy in Patients With Type 2 Diabetes Mellitus

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05310916
• Other study ID #: 311311
• Status: Recruiting
• Phase: Phase 3
• Start date: June 6, 2022
• Est. completion date: November 2023

Study information

• Verified date: June 2022
• Source: Ain Shams University
• Contact: Nidae A Ismail, BSc
• Phone: 00201157820751
• Email: Nidae.Alaa[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

A prospective, randomized, open-label, controlled clinical trial will be conducted at the endocrinology department - Ain Shams University (ASU) hospital. Sixty patients will be enrolled into the study. 30 of which will receive dapagliflozin 10mg tab once daily and the other thirty will receive their standard antidiabetic therapy for 12 weeks.

Description:

All type 2 diabetes mellitus patients presenting to the endocrinology department, ASU Hospitals, who were diagnosed with mild to moderate non-proliferative diabetic retinopathy will be assessed for eligibility.

Eligible patients will be randomly assigned to one of the following 2 arms:

1. Group 1 (Control group) (n= 30): type 2 diabetes mellitus patients who will receive their oral antidiabetic for 12 weeks.

2. Group 2 (Test group) (n= 30): type 2 diabetes mellitus patients who will receive their oral antidiabetic along with dapagliflozin at a dose of 10 mg daily for 12 weeks.

A total of four visits one for baseline evaluation and one for end of study evaluation and two intermediate visits, the following will be performed in the visits:

1. Clinical Evaluation

1. Systolic and diastolic blood pressures recording.

2. Plasma glucose measurement.

2. Report any adverse effects that may appear

3. Blood samples will be taken at baseline and at 12-week visits

4. Follow up

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: November 2023
• Est. primary completion date: May 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 70 Years

Eligibility

Inclusion Criteria:

1. Female or male aged between 40 and 70 years old.

2. Glomerular filtration rates > 60 mL/min.

3. Normal aspartate and alanine transaminase levels.

4. Controlled systolic and diastolic blood pressures

Exclusion Criteria:

1. Patients using insulin or more than one oral anti-diabetic drug.

2. Patients who have HbA1c level =10% (86 mmol/mol) or a fasting plasma glucose level >240 mg/dl.

3. Patients with a history of cardiovascular events within six months before enrolment.

4. Patients suffering from cataract or glaucoma.

5. Patients with volume depletion clinical signs.

6. Body mass index (BMI) >40 kg/m2

7. Infectious or inflammatory diseases.

8. Neoplasm, or hematological disorders.

9. Pregnant or breast-feeding patients.

10. Active participation in another clinical study.

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Diabetic Retinopathy
• Retinal Diseases

Intervention

Drug:
• Dapagliflozin 10mg Tab plus another oral hypoglycemic agent
Dapagliflozin is a member of Sodium-glucose co-transporter 2 inhibitors class which in addition to its glucose control effect, has reno-protective and cardioprotective effects, controls blood pressure and causes weight loss.
• Two oral hypoglycemic agents other than dapagliflozin
Two oral anti-diabetic agents not including sodium-glucose co-transporter 2 inhibitors

Locations

Country	Name	City	State
Egypt	Internal medicine and endocrinology department, Ain-shams university hospitals	Cairo

Sponsors (1)

Lead Sponsor	Collaborator
Nidae Alaa

Country where clinical trial is conducted

Egypt, 

References & Publications (9)

Chen YY, Wu TT, Ho CY, Yeh TC, Sun GC, Kung YH, Wong TY, Tseng CJ, Cheng PW. Dapagliflozin Prevents NOX- and SGLT2-Dependent Oxidative Stress in Lens Cells Exposed to Fructose-Induced Diabetes Mellitus. Int J Mol Sci. 2019 Sep 5;20(18). pii: E4357. doi: 10.3390/ijms20184357. — View Citation

Lahoti S, Nashawi M, Sheikh O, Massop D, Mir M, Chilton R. Sodium-glucose co-transporter 2 inhibitors and diabetic retinopathy: insights into preservation of sight and looking beyond. Cardiovasc Endocrinol Metab. 2020 May 18;10(1):3-13. doi: 10.1097/XCE.0000000000000209. eCollection 2021 Mar. Review. — View Citation

Ott C, Jumar A, Striepe K, Friedrich S, Karg MV, Bramlage P, Schmieder RE. A randomised study of the impact of the SGLT2 inhibitor dapagliflozin on microvascular and macrovascular circulation. Cardiovasc Diabetol. 2017 Feb 23;16(1):26. doi: 10.1186/s12933-017-0510-1. — View Citation

Peters AL, Buschur EO, Buse JB, Cohan P, Diner JC, Hirsch IB. Euglycemic Diabetic Ketoacidosis: A Potential Complication of Treatment With Sodium-Glucose Cotransporter 2 Inhibition. Diabetes Care. 2015 Sep;38(9):1687-93. doi: 10.2337/dc15-0843. Epub 2015 Jun 15. — View Citation

Sha W, Wen S, Chen L, Xu B, Lei T, Zhou L. The Role of SGLT2 Inhibitor on the Treatment of Diabetic Retinopathy. J Diabetes Res. 2020 Nov 12;2020:8867875. doi: 10.1155/2020/8867875. eCollection 2020. Review. — View Citation

Wong TY, Cheung CM, Larsen M, Sharma S, Simó R. Diabetic retinopathy. Nat Rev Dis Primers. 2016 Mar 17;2:16012. doi: 10.1038/nrdp.2016.12. Review. — View Citation

Yao Y, Li R, Du J, Long L, Li X, Luo N. Interleukin-6 and Diabetic Retinopathy: A Systematic Review and Meta-Analysis. Curr Eye Res. 2019 May;44(5):564-574. doi: 10.1080/02713683.2019.1570274. Epub 2019 Feb 4. — View Citation

Zheng Y, Ley SH, Hu FB. Global aetiology and epidemiology of type 2 diabetes mellitus and its complications. Nat Rev Endocrinol. 2018 Feb;14(2):88-98. doi: 10.1038/nrendo.2017.151. Epub 2017 Dec 8. Review. — View Citation

Zhou Z, Ju H, Sun M, Chen H. Serum Vascular Endothelial Growth Factor Levels Correlate with Severity of Retinopathy in Diabetic Patients: A Systematic Review and Meta-Analysis. Dis Markers. 2019 Mar 24;2019:9401628. doi: 10.1155/2019/9401628. eCollection 2019. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Severity of retinopathy	evaluate the change of stage of disease according to diabetic retinopathy severity scale,, Which is the International Clinical Disease Severity Scale (ICDSS) for DR. This scale classified the severity of disease into five stages ( No apparent retinopathy, Mild Non proliferative Diabetic retinopathy (NPDR) ,Mod NPDR, Severe NPDR ,Proliferative Diabetic Retinopathy) depend on eye examination. higher scores mean worse outcome.	12 weeks
Primary	Evaluation of the study biomarkers, IL-6, and VEGF	Interleukin-6 (IL-6)//inflammatory biomarker Vascular endothelial growth factor (VEGF)//angiogenic biomarker	12 weeks
Secondary	Occurrence of adverse events	No potential risks are expected when the study patients are selected according to the determined inclusion criteria but maybe occur Nausea, abdominal pain, polyuria, thrush, genital or urinary tract infections	(1-90)days

External Links

•   Protective Effect of Sodium-Glucose Co-Transporter 2 Inhibitor (Dapagliflozin) on Diabetic Retinopathy in Streptozotocin Induced Diabetes in Rats