Can Mounjaro Worsen Diabetic Retinopathy?
Yes, Mounjaro (tirzepatide) can cause early worsening of diabetic retinopathy through rapid improvement in glycemic control, particularly in patients with pre-existing retinopathy and poor baseline glucose control. This phenomenon is well-established with intensive glucose-lowering therapies, including GLP-1 receptor agonists like Mounjaro.
Mechanism of Early Worsening
- Rapid glycemic improvement paradoxically worsens retinopathy in the short term before long-term benefits emerge 1.
- The Diabetes Control and Complications Trial (DCCT) demonstrated that intensive therapy initially increased retinopathy progression during the first year, with higher cumulative incidence of sustained progression in the intensive group compared to conventional treatment 1.
- After 36 months, the intensive group showed lower progression risks, with intensive therapy ultimately reducing retinopathy progression by 54% (95% CI 39–66) 1.
Evidence Specific to GLP-1 Receptor Agonists
- GLP-1 RAs including liraglutide, semaglutide, and dulaglutide have been associated with increased risk of rapidly worsening diabetic retinopathy in randomized trials 1.
- The association between GLP-1 RA treatment and retinopathy occurs primarily through rapid A1C reduction at 3-month and 1-year follow-up 1.
- While meta-analyses show no association between GLP-1 RA treatment and retinopathy per se, the rapid glucose reduction mechanism applies to all intensive glucose-lowering therapies, including Mounjaro 1.
Clinical Risk Factors
Patients at highest risk for early worsening include those with:
- Pre-existing diabetic retinopathy of any severity 1, 2
- Poor baseline glycemic control (high A1C) 2, 3
- Large and rapid reductions in blood glucose levels 2
- Hypertension 1, 3
- Long diabetes duration 1
Clinical Management Recommendations
Before initiating Mounjaro:
- Assess retinopathy status when intensifying glucose-lowering therapies, since rapid A1C reductions can be associated with initial worsening of retinopathy 1.
- Obtain dilated comprehensive eye examination by an ophthalmologist or optometrist if not performed within the past year 1.
During treatment:
- Promptly refer patients with any level of diabetic macular edema, moderate or worse nonproliferative diabetic retinopathy, or any proliferative diabetic retinopathy to an ophthalmologist 1.
- Monitor more frequently (every 3-6 months initially) in patients with pre-existing retinopathy who are started on Mounjaro 1.
- The early worsening is transitory and reversible, with long-term glycemic control ultimately decreasing the risk of diabetic retinopathy and neuropathy 4.
Important Caveats
- The phenomenon of early worsening does not negate the long-term benefits of improved glycemic control 1.
- After the initial period of potential worsening (typically first 12-36 months), intensive glycemic control reduces retinopathy risk by 54-76% 1.
- The presence of retinopathy is not a contraindication to Mounjaro use, but requires closer ophthalmologic monitoring 1.
- Pregnancy can also aggravate retinopathy, especially when glycemic control is poor at conception, requiring additional vigilance in women of childbearing potential 1.
In patients with established moderate-to-severe retinopathy, consider ophthalmology consultation before initiating Mounjaro to establish baseline severity and monitoring plan 1.