What alternative treatment options are available for a patient with type 2 diabetes and impaired renal function who experienced vision changes while on Ozempic (semaglutide)?

Alternative Treatment for Type 2 Diabetes with Impaired Renal Function After Semaglutide-Related Vision Changes

Given the patient's vision changes on semaglutide and impaired renal function, switch to an SGLT2 inhibitor as the preferred alternative, specifically canagliflozin (which can be used down to eGFR 30 ml/min/1.73 m² in diabetic kidney disease) or empagliflozin, as these agents provide cardiovascular and renal protection without the retinopathy risks associated with GLP-1 receptor agonists. 1

Understanding the Vision Changes with Semaglutide

The American College of Cardiology explicitly identifies history of proliferative retinopathy as a consideration that may prompt use of an alternative class to semaglutide or dulaglutide. 1 The FDA label instructs patients to contact their physician if changes in vision are experienced during treatment with semaglutide. 2

• The mechanism appears related to rapid A1C reduction rather than direct drug toxicity, with worsening retinopathy particularly seen in patients with poor baseline glycemic control (HbA1c >9%) and pre-existing proliferative retinopathy. 3
• Recent case reports have also linked semaglutide to non-arteritic anterior ischemic optic neuropathy (NAION), though causality remains under investigation. 4
• The vision changes warrant permanent discontinuation of semaglutide in this patient. 3

Optimal Alternative: SGLT2 Inhibitors

Why SGLT2 Inhibitors Are Preferred

SGLT2 inhibitors should be the first-line alternative because they provide:

• Cardiovascular risk reduction comparable to GLP-1 receptor agonists in patients with atherosclerotic cardiovascular disease 1
• Superior renal protection with demonstrated benefits in diabetic kidney disease 1
• No retinopathy risk, making them ideal for patients with vision concerns 1
• Usability in moderate-to-severe renal impairment: Canagliflozin is FDA-approved down to eGFR 30 ml/min/1.73 m² specifically for diabetic kidney disease 1

Specific SGLT2 Inhibitor Selection Based on Renal Function

If eGFR is 30-45 ml/min/1.73 m²:

• Use canagliflozin as it has FDA approval for use in this range specifically for diabetic kidney disease 1
• Note that glycemic efficacy decreases below eGFR 45 ml/min/1.73 m², but renal and cardiovascular benefits persist 1

If eGFR is >45 ml/min/1.73 m²:

• Any SGLT2 inhibitor (empagliflozin, dapagliflozin, canagliflozin) is appropriate 1
• Choose based on cardiovascular or heart failure comorbidities 1

Critical Precautions When Initiating SGLT2 Inhibitors

• Avoid in patients with active diabetic foot ulcers or severe peripheral arterial disease if considering canagliflozin specifically 1
• Use clinical judgment when starting if the patient is on or starting ACE inhibitors/ARBs with impaired renal function, as transient eGFR decline may occur 1
• Educate regarding genital mycotic infections and importance of genital hygiene 1
• Monitor for volume depletion: May need to reduce diuretic dose; instruct patients to hold medication if experiencing dehydration symptoms 1
• Reduce insulin or sulfonylurea doses by ~20% at initiation to prevent hypoglycemia 1

Alternative GLP-1 Receptor Agonists: Use with Extreme Caution

If SGLT2 inhibitors are contraindicated or not tolerated, alternative GLP-1 receptor agonists could theoretically be considered, but this carries significant risk given the vision changes.

If Considering Another GLP-1 RA (Not Recommended as First Choice):

Liraglutide or exenatide might be alternatives, as they were not specifically flagged for retinopathy concerns in the American College of Cardiology guidelines (unlike semaglutide and dulaglutide). 1

However, this approach requires:

• Mandatory comprehensive dilated eye examination before initiation to document current retinopathy status 3
• Very slow dose titration to minimize rapid A1C reduction 3
• Concurrent 20% reduction in insulin dose if on insulin therapy 3
• Ophthalmologic monitoring every 6 months rather than annually 3
• Patient must understand the risk of retinopathy worsening, particularly if proliferative retinopathy is present 3

For Severe Renal Impairment (eGFR <30 ml/min/1.73 m²):

If eGFR falls below 30 ml/min/1.73 m², GLP-1 receptor agonists become the preferred option over SGLT2 inhibitors for kidney disease management. 1 However, given this patient's vision changes:

• Avoid semaglutide and dulaglutide due to retinopathy concerns 1, 3
• Consider liraglutide or exenatide with the precautions outlined above 1
• Oral semaglutide has been studied in moderate renal impairment (eGFR 30-59 ml/min/1.73 m²) with acceptable safety, but given the vision changes, this should be avoided 5

Additional Therapeutic Considerations

Baseline Glycemic Agents to Continue/Optimize:

• Metformin: Continue if eGFR >30 ml/min/1.73 m²; reduce dose if eGFR 30-45 ml/min/1.73 m²; discontinue if eGFR <30 ml/min/1.73 m² 1
• Basal insulin: Optimize dosing but reduce by ~20% when adding SGLT2 inhibitor 1
• Avoid or minimize sulfonylureas due to hypoglycemia risk, especially with impaired renal function 1

Monitoring After Switching to SGLT2 Inhibitor:

• Home glucose monitoring for first 4 weeks, especially if on insulin or sulfonylureas 1
• Renal function at 2-4 weeks after initiation (expect transient eGFR decline of 2-5 ml/min/1.73 m²) 6, 7
• Volume status and blood pressure at each visit 1
• Foot examination at each visit if on canagliflozin 1

Common Pitfalls to Avoid

• Do not restart any GLP-1 RA without ophthalmologic clearance and documentation of current retinopathy status 3
• Do not use SGLT2 inhibitors in patients with recurrent genital candidiasis or active diabetic foot ulcers (particularly canagliflozin) 1
• Do not aggressively reduce A1C if retinopathy is present, regardless of agent chosen 3
• Do not overlook the cardiovascular benefits of both SGLT2 inhibitors and GLP-1 RAs when making treatment decisions 1, 7