DPP-4 inhibitors show no clear effect on diabetic eye disease risk

Methodology

Researchers searched five major medical databases through July 2023 for studies comparing DPP-4 inhibitor users with non-users. They included seven observational studies from Taiwan, Korea, Germany, the USA, and Denmark. Study sizes ranged from 48 to over 126,000 people with type 2 diabetes. Average participant age was 57-77 years, with diabetes lasting 3-8 years in most cases.

Eye disease was identified mainly through diagnosis codes in medical records, with one study using detailed grading scales. Follow-up ranged from 2 to 10 years. Four studies used matching techniques to make the groups more similar. Two reviewers independently checked study quality. The team combined results from all studies while accounting for differences between them.

Interventions

The studied group included people with type 2 diabetes taking DPP-4 inhibitors, a class of diabetes pills that work by affecting hormones involved in blood sugar control. These medications include sitagliptin, vildagliptin, saxagliptin, linagliptin, alogliptin, and gemigliptin. They can be used alone or with other diabetes medications.

Most studies required people to be on the medication for at least 3-6 months. These pills are often used when first-line medications aren't enough, and they typically don't cause weight gain or low blood sugar. Comparison groups included people taking other diabetes medications like sulfonylureas, metformin, or thiazolidinediones.

Key Findings

Seven studies found no clear difference in eye disease risk between people taking DPP-4 inhibitors and those on other diabetes medications. For new eye disease cases, four studies showed DPP-4 inhibitors neither increased nor decreased risk. For worsening of existing eye disease, three studies again showed no clear difference. Individual study results were mixed, with most showing no effect either way. Results varied considerably between studies, which may reflect differences in patient groups or how eye disease was measured.

Comparison with other Studies

These findings differ somewhat from a previous analysis of clinical trials, which suggested DPP-4 inhibitors might increase eye disease risk. However, the difference likely reflects the controlled trial setting versus real-world use captured in observational studies.

Two large trials called TECOS and CARMELINA found similar results to this review, showing no clear increase in eye problems with DPP-4 inhibitors. A small study even suggested potential benefits for eye blood flow. Laboratory research shows conflicting results about how these medications might affect eye tissue. Other diabetes medications like SGLT2 inhibitors and GLP-1 drugs also appear neutral for eye disease risk.

Journal Reference

Wang M, Lu J, Dong J. Association between dipeptidyl peptidase-4 inhibitor use and diabetic retinopathy: a systematic review and meta-analysis of real-world studies. BMC Ophthalmol. 2024;24:272. doi:10.1186/s12886-024-03535-1