TOP LINE:

Empagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, did not reduce the risk of incident nonproliferative diabetic retinopathy compared to dipeptidyl peptidase 4 (DPP-4) inhibitors in patients with type 2 diabetes, but the drug reduced the risk of its progression by 22% in patients with existing retinopathy.

METHODOLOGY:

• Researchers conducted an active comparator cohort study of new users using U.S. insurance claims data between August 2014 and September 2019 to compare risk of incident nonproliferative diabetic retinopathy and progression of diabetic retinopathy in patients with type 2 diabetes starting with empagliflozin or a DPP-4 inhibitor. .
• They included 34,239 pairs of propensity score-matched type 2 diabetic patients (52.4% men; mean age: 65.6 years) without a history of retinopathy.
• The 7,831 couples (52.5% men; mean age 67 years) of diabetic patients included in the diabetic retinopathy progression cohort were required to have a history of nonproliferative diabetic retinopathy.
• Outcome measures included incident nonproliferative diabetic retinopathy, defined by diagnosis codes, and progression of diabetic retinopathy, defined as a composite of treatment initiation or occurrence of vitreous hemorrhage or of proliferative diabetic retinopathy.

TAKE AWAY:

• During an average follow-up period of 8 months, researchers observed no significant differences in the risk of incident nonproliferative diabetic retinopathy between the groups taking empagliflozin or a DPP-4 inhibitor ( hazard ratio (HR), 1.04; 95% CI, 0.94 -1.15).
• Initiation of empagliflozin was associated with a lower risk of progression of diabetic retinopathy compared to initiation of a DPP-4 inhibitor (HR: 0.78; 95% CI, 0.63 -0.96).
• Results remained consistent across multiple subgroups of gender, age, race, ethnicity, smoking, baseline hypertension, hyperlipidemia, diabetic neuropathy and nephropathy, insulin use and uncontrolled diabetes.

IN PRACTICE:

“Our study may be useful in assessing the potential risks and benefits of various glucose-lowering treatments in patients with (type 2 diabetes) who are at high risk of developing DR (diabetic retinopathy) or among those with DR pre-existing”, the authors wrote the study.

In a editorial accompanying the journal articleJonathan E. Shaw, MD, and Alicia J. Jenkins, MD, of the Baker Heart and Diabetes Institute, Melbourne, Australia, speculate that the apparent advantage of the SGLT2 inhibitor over the DPP-4 agent may be a by-product of the latter. the relatively limited ability of the drug to reduce blood sugar.

“The weaker glucose-lowering effect of the DPP-4 inhibitors may have meant that more people in this group were subsequently switched to what was likely a third- or fourth-line glucose-lowering drug. Insulin receptor and glucagon-like peptide 1 agonists are often used in this role, are the most potent hypoglycemic drugs, and have both (along with other therapies) been associated with early worsening of DR (diabetic retinopathy) which can occur (3 months to 3 years) after rapid improvement in blood sugar control,” they wrote. “Thus, the apparent benefit of empagliflozin might actually result from damage in the comparator arm. The relatively high baseline hemoglobin A1c(HbA1c) in this cohort, the short follow-up, and the fact that apparent benefits were only observed for DR progression and not DR incidence are all consistent with this hypothesis.

The authors added: “Not all ophthalmologists are comfortable prescribing systemic medications such as fenofibrate and empagliflozin. As the evidence base for these agents continues to grow, this will need to change, either by taking on this task directly or by developing communication and partnerships with primary care physicians and other physicians to ensure prescribing and monitoring appropriate. Additionally, in resource-limited settings, where retinal laser equipment and intravitreal medications and associated trained eye clinicians may not be readily accessible or affordable, oral glucose-lowering and lipid-modulating medications may be an affordable option to limit the progression of DR.

SOURCE:

This study was led by Helen Tesfaye, PharmD, MSc, of the Department of Medicine at Brigham and Women’s Hospital, Harvard Medical School, in Boston. It was published online on December 5, 2024, at JAMA Ophthalmology.

BOUNDARIES:

The presence of unmeasured or residual confounding cannot be excluded. Misclassification of results may have occurred due to reliance on diabetic retinopathy diagnosis codes in claims, and some progression events, including transition from mild to moderate nonproliferative diabetic retinopathy, may not not have been taken into account. The relatively short follow-up period of approximately 8 months may have affected the observation of potential differences between treatment groups, particularly in terms of outcomes related to nonproliferative diabetic retinopathy.

DISCLOSURES:

This study was supported by a research grant from Boehringer Ingelheim at Brigham and Women’s Hospital. Some authors disclosed receiving grants, being employed, and holding stock from various sources, including the funding agency.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.