Ertugliflozin 5mg is NOT a Sufficient Alternative to Empagliflozin (Jardiance) 10mg
Ertugliflozin 5mg does not provide equivalent cardiovascular and renal protection compared to empagliflozin 10mg, and you should advocate strongly with the insurance company for empagliflozin coverage based on proven mortality benefits that ertugliflozin lacks.
Critical Evidence Gap: Cardiovascular Outcomes
The fundamental problem is that empagliflozin has proven cardiovascular mortality reduction while ertugliflozin does not:
Empagliflozin 10mg reduces cardiovascular death by 38% (HR 0.62,95% CI 0.49-0.77) and all-cause mortality by 32% (HR 0.68,95% CI 0.57-0.82) in patients with type 2 diabetes and established cardiovascular disease 1, 2
Empagliflozin reduces hospitalization for heart failure by 35% and reduces major adverse cardiovascular events (MACE) with a hazard ratio of 0.86 1, 2
Ertugliflozin showed only non-inferiority (not superiority) for cardiovascular outcomes in the VERTIS CV trial, meaning it did NOT demonstrate the mortality benefits that empagliflozin has proven 1
Glycemic Control: Potentially Comparable but Context-Dependent
For glucose-lowering alone, the comparison is more nuanced:
Network meta-analysis shows ertugliflozin 5mg has similar HbA1c reduction to other low-dose SGLT2 inhibitors when used as monotherapy 3
When added to metformin, ertugliflozin 5mg was actually more effective than dapagliflozin 5mg (mean difference -0.22%, 95% CrI -0.42, -0.02) 3
However, empagliflozin's recommended dose is 10mg once daily with no titration needed for cardiovascular or renal benefits 1, 2
Renal Protection: Insufficient Evidence for Ertugliflozin
The renal protection data strongly favors empagliflozin:
Empagliflozin reduced the risk of a prespecified renal composite outcome by 50% (HR 0.50; 95% CI 0.32-0.77) in patients with prevalent kidney disease 2
Ertugliflozin showed a 34% reduction in the exploratory kidney composite endpoint (HR 0.66,95% CI 0.50-0.88), but this was an exploratory outcome, not a primary endpoint 4
KDIGO 2020 guidelines specifically recommend SGLT2 inhibitors with documented kidney or cardiovascular benefits 1, and empagliflozin has stronger evidence than ertugliflozin
Dosing Equivalence Issues
The proposed substitution has dose-related concerns:
Empagliflozin 10mg is the standard starting dose that provides full cardioprotective benefit without need for titration 1, 5, 2
Ertugliflozin 5mg is the lower dose; the 15mg dose showed better HbA1c reduction in some comparisons 3
There is no established dose equivalence between ertugliflozin 5mg and empagliflozin 10mg for cardiovascular protection 3, 6
Safety Profile: Generally Similar but Important Caveats
Both medications share the SGLT2 inhibitor class safety profile:
Ertugliflozin was generally well tolerated with genital mycotic infections (9.1% for 5mg vs 3.0% placebo in females; 3.7% vs 0.4% in males) 7
Three cases of ketoacidosis occurred with ertugliflozin 15mg and no cases of Fournier's gangrene in pooled phase 3 trials 7
Ertugliflozin has a specific caution for amputation risk (similar to canagliflozin), which empagliflozin does not carry 1
Volume depletion risk was increased with ertugliflozin in patients with eGFR <60 mL/min/1.73 m², age ≥65 years, or on diuretics 7
Clinical Decision Algorithm
If your patient has established cardiovascular disease or heart failure:
- Empagliflozin 10mg is NOT interchangeable with ertugliflozin 5mg due to proven mortality benefits 1, 2
- Submit a prior authorization appeal citing the EMPA-REG OUTCOME trial showing 32% all-cause mortality reduction 1, 2
- Alternative: Consider canagliflozin 100mg or dapagliflozin 10mg if empagliflozin is denied, as these have cardiovascular outcome trial data 1, 5
If your patient has chronic kidney disease with albuminuria:
- Empagliflozin has stronger renal protection evidence (50% risk reduction) 2
- Ertugliflozin's renal data comes from exploratory endpoints only 4
- Appeal based on superior renal protection evidence 1, 2
If the indication is purely glycemic control without cardiovascular/renal disease:
- Ertugliflozin 5mg may provide adequate glucose-lowering 3, 6
- However, you should still advocate for empagliflozin given the potential for unrecognized cardiovascular benefit 1, 5
Common Pitfalls to Avoid
Do not accept "all SGLT2 inhibitors are the same" - the cardiovascular mortality data is specific to empagliflozin, canagliflozin, and dapagliflozin, NOT ertugliflozin 1
Do not assume dose equivalence - ertugliflozin 5mg is not proven equivalent to empagliflozin 10mg for cardioprotection 3, 6
Do not forget to check eGFR - empagliflozin should not be initiated if eGFR <45 mL/min/1.73 m² 1, 2, while ertugliflozin can be used down to eGFR 30 mL/min/1.73 m² 6
Document the specific indication - if prescribing for cardiovascular risk reduction (not just glucose control), this strengthens your appeal for empagliflozin 1, 2
Practical Appeal Strategy
When submitting the prior authorization appeal, include:
- Patient's cardiovascular disease status or heart failure diagnosis 1
- Cite EMPA-REG OUTCOME trial showing 38% cardiovascular death reduction and 32% all-cause mortality reduction 1, 2
- Reference ACC/AHA guidelines recommending SGLT2 inhibitors with proven cardiovascular benefit 1, 5
- Note that ertugliflozin only showed non-inferiority, not superiority for cardiovascular outcomes 1
- Emphasize that this is not about cost but about proven mortality benefit 1, 2