SGLT2-inhibition With Empagliflozin Reduces Progression of Diabetic Retinopathy in Patients With High Risk of Diabetic Macular Edema (The SUPER-Trial)
Overview
- Phase
- Phase 4
- Intervention
- Empagliflozin
- Conditions
- Diabetes Mellitus, Type II
- Sponsor
- Hannover Medical School
- Enrollment
- 6
- Locations
- 1
- Primary Endpoint
- Microaneurysm formation rate over 12 months, i.e. number of newly developed microaneurysms within 12 months
- Status
- Terminated
- Last Updated
- 7 years ago
Overview
Brief Summary
This is a prospective, randomized, active control, two-arm parallel, double-blind, monocenter phase IV clinical trial. The trial compares empagliflozin to glimepiride in patients with type 2 diabetes mellitus in addition to standard of care treatment.
Patients with type 2 diabetes mellitus who are between 18 and 80 years of age will be recruited for the clinical trial and randomly allocated to either receive empagliflozin or glimepiride.
The assumption of the study is that empagliflozin slows down diabetic retinopathy progression rate and thus a lower microaneurysm formation rate compared to subjects treated with glimepiride by substantially decreased cellular glucotoxicity will be achieved.
Investigators
Eligibility Criteria
Inclusion Criteria
- •women and men between 18 - 80 years of age
- •type 2 diabetes mellitus
- •early to moderate stage diabetic retinopathy (ETDRS: 20 (microaneurysms only) to 35 (microaneurysms/ hemorrhages and/or hard exsudates)) in one or both eyes
- •stable HbA1c (± 0.5%) for at least 12 weeks
- •antidiabetic treatment with either diet, metformin, DPP4, GLP1, pioglitazone, acarbose, or respective combinations
- •HbA1c ≥ 6.5 and ≤ 10.0 %
- •body mass index \< 46 kg/m2
- •office blood pressure ≤ 150/95 mmHg (confirmed on a second day; 24h ambulatory blood pressure measurement (ABPM) is allowed to check accuracy of office values; inclusion with 24h mean blood pressure ≤ 145/90 mm Hg is possible); patients with hypertension should be treated according to current treatment guidelines
- •either women without childbearing potential defined by:
- •at least 6 weeks after surgical sterilization by bilateral tubal ligation or bilateral oophorectomy
Exclusion Criteria
- •Type 1 diabetes
- •uncontrolled diabetes mellitus type 2 with fasting glucose \> 13.3 mmol/l confirmed on a second day
- •known or suspected hypersensitivity to empagliflozin, glimepiride, or any excipients; and / or known or suspected hypersensitivity to sulfonylureas, sulfonamides or SGLT2 inhibitors in general
- •history of multiple severe hypoglycemic episodes within the last two years
- •use of Insulin, SGLT2-inhibitor, sulfonylurea derivate or a glinide within past 3 months
- •clinical significant macular edema in both eyes and indication for intravitreal anti-VEGF treatment for both eyes at screening or baseline visit. Eyes with a small amount of intraretinal or subretinal fluid (seen in OCT) but no need for intravitreal treatment as judged by the investigator (according to current practice patterns) may be included. Eyes with a history of intravitreal treatment of macular edema which do not need ongoing intravitreal treatment at the time of screening may be included.
- •eye diseases or pathologies that prevent clear ophthalmoscopy and evaluation of study parameters, thus not allowing study participation according to the investigator´s judgment, such as (but not only) vitreous hemorrhage, mature cataract, macular pathologies other than diabetic maculopathy
- •history of ketoacidosis or metabolic acidosis
- •use of loop diuretics
- •history of \> 1 urogenital infection/year
Arms & Interventions
Empagliflozin/glimepiride placebo
Empagliflozin 25 mg film-coated tablet p.o. daily and glimepiride matching placebo p.o. daily Duration of treatment: 12 months
Intervention: Empagliflozin
Empagliflozin/glimepiride placebo
Empagliflozin 25 mg film-coated tablet p.o. daily and glimepiride matching placebo p.o. daily Duration of treatment: 12 months
Intervention: Glimepiride placebo
Glimepiride/empagliflozin placebo
Glimepiride 2 mg tablet p.o. daily and empagliflozin matching placebo p.o. daily Duration of treatment: 12 months
Intervention: Glimepiride
Glimepiride/empagliflozin placebo
Glimepiride 2 mg tablet p.o. daily and empagliflozin matching placebo p.o. daily Duration of treatment: 12 months
Intervention: Empagliflozin placebo
Outcomes
Primary Outcomes
Microaneurysm formation rate over 12 months, i.e. number of newly developed microaneurysms within 12 months
Time Frame: Weeks 27 and 52
Secondary Outcomes
- Microaneurysm formation rate after 6 months (compared to baseline)(after 6 months)
- Change in diabetic retinopathy stage (≥ 2 step change on ETDRS severity score)(Weeks 27 and 52)
- Change in microaneurysm count(Weeks 27 and 52)
- Change in retinal thickness (as measured by Optical Coherence Tomography)(Weeks 27 and 52)
- Change in retinal perfusion of microvasculature within the retina (flow in Optical Coherence Tomography Angiography)(Weeks 27 and 52)
- Progression to clinically significant macular edema (CSME)(Up to 52 weeks)
- Change in intraocular lipid content (hard exsudates)(Weeks 27 and 52)
- Change in composite clinical outcome evaluating progression to proliferative diabetic retinopathy (PDR) based on photography, angiography plus clinically important events defining PDR (e.g. vitreous haemorrhage)(Weeks 27 and 52)
- Change in best corrected visual acuity (BCVA [ETDRS letters])(Weeks 27 and 52)
- Change in HbA1c(Weeks 2, 7, 12, 17, 22, 27, 32, 37, 42, 47, 52 and 55)
- Change in fasting glucose(Weeks 2, 7, 12, 17, 22, 27, 32, 37, 42, 47, 52 and 55)
- Change in body weight and body fat mass(Weeks 27, 52 and 55)
- Change in ambulatory blood pressure(Weeks 27 and 52)