Dr. Ahmed Invokana Vs Jardiance is a comparison of two potent SGLT-2 Inhibitors: Canagliflozin vs Empagliflozin.
Canagliflozin (Invokana) and Empagliflozin (Jardiance) both belong to the same drug class, that is, Sodium Glucose Co-transport-2 Inhibitors (SGLT2i).
These drugs are commonly used to treat patients with Type 2 diabetes, especially those who have kidney disease, heart failure, hypertension, and are overweight.
Canagliflozin (Invokana) is considered the most potent SGLT2 Inhibitor as it lowers the A1C the most, however, its effects on bone density and increased risk of fractures have limited its use.
Jardiance, on the other hand, although slightly less potent than Invokana, has got FDA approval for use in heart failure with preserved and reduced ejection fraction and kidney disease, even in non-diabetic individuals.
Uses of Canagliflozin (Invokana):
Canagliflozin is beneficial in the following conditions:
- To improve blood sugar levels in people with type 2 diabetes
- To lower the risk of cardiovascular events in people with type 2 diabetes
- In patients with End Stage Renal Disease (ESRD)
Uses of Empagliflozin (Jardiance)
Empagliflozin can be used in the treatment of the following conditions:
- To improve blood glucose levels in type 2 diabetes
- To lower the risk of CVD in adults with type 2 diabetes
- To lower the risk of heart failure and the need for hospitalizations in patients with a reduced ejection fraction
- Treatment of adults with heart failure regardless of Ejection fraction (reduced and preserved ejection fraction)
- As a supplemental drug for chronic kidney disease.
Note: Both drugs cannot be used for the treatment of type 1 Diabetes Mellitus
Clinical Efficacy of Invokana Vs Jardiance:
In a meta-analysis, the clinical efficacy of SGLT2 inhibitors was studied, and the study concluded that both the medications (Canagliflozin and empagliflozin) have similar effects in decreasing HbA1c levels. The study also concludes that increasing the dosage had no effect in further decreasing the HbA1c levels. [Ref]
Another study concluded that Canagliflozin 300 mg monotherapy was associated with greater A1C reductions than dapagliflozin and empagliflozin; however, differences between SGLT2 inhibitors were smaller with metformin combination therapy.[Ref]
In clinical studies involving patients with type 2 diabetes mellitus and a history or high risk of cardiovascular events.
SGLT2 Inhibitor | Dose | Percentage A1C reduction |
| Canagliflozin | 100 mg | ↓ 0.91% |
| 300 mg | ↓ 1.16% | |
| Empagliflozin | 10 mg | ↓ 0.7% |
| 25 mg | ↓ 0.8% |
Empagliflozin was found to reduce the risk of death from any cause and heart failure hospitalization. Canagliflozin delayed the onset of albuminuria and the composite outcome of a sustained 40% reduction in eGFR, the need for renal replacement therapy, or death from renal causes. [Ref]
Overall, studies suggest that canagliflozin had better reductions in HbA1c, FPG and body weight. It was also found to reduce the number of CVD events in people with type 2 diabetes.
However, empagliflozin had a better efficacy among patients with Heart Failure. In addition, it has been approved in adults with heart failure regardless of ejection fraction (including patients with heart failure and a preserved ejection fraction).
Lately, the FDA also approved Jardiance (Empagliflozin) to prevent the progression of kidney disease in adults with CKD [Ref]
Invokana Vs Jardiance weight loss comparison:
Both Invokana and Jardiance are associated with significant weight loss in comparison to a placebo drug.
The weight loss effects depend on the dose of the drug used. Weight loss associated with Invokana and Jardiance is tabulated here:
| SGLT2 Inhibitor | Dose | Most Potent Weight Loss Drug |
| Canagliflozin | 300 mg | ↓ 3.3 kg |
| Empagliflozin | 25 mg | ↓ 2.8 kg |
| Empagliflozin | 10 mg | ↓ 2.4 kg |
| Canagliflozin | 100 mg | ↓ 2.2 kg |
Side Effects of Invokana Vs Jardiance:
Invokana | Jardiance |
|
|
Drug Interactions – Invokana Vs Jardiance:
Canagliflozin interacts with some medications used to treat CVD these include Lanoxin (digoxin), and it also interacts with UGT inducers (drugs that are metabolized by specific enzymes) such as rifampin, phenytoin, phenobarbital, and ritonavir.
Both canagliflozin and empagliflozin interact with diuretics such as Lasix (furosemide) and hydrochlorothiazide, as well as other diabetic medications such as metformin.
The drug history of patients should be recorded before recommending SGLT2 inhibitors to avoid interactions.
Drug | Invokana | Jardiance |
| Phenytoin | Yes | No |
| Phenobarbital | Yes | No |
| Ritonavir | Yes | No |
| Lanoxin (digoxin) | Yes | No |
| Lasix (furosemide) Hydrochlorothiazide | Yes | Yes |
| Glucophage (metformin) | Yes | Yes |
Additional Warnings and Precautions
As both drugs belong to the same class, they have some common warnings and precautions.
Dehydration:
Both canagliflozin and empagliflozin should be administered with caution in patients using diuretics because of the increased risk of dehydration.
Euglycemic Ketoacidosis:
Ketoacidosis is another complication that is associated with all SGLT2 inhibitors. This condition can be life-threatening, and some of the symptoms are nausea, fruity breath, confusion, and abdominal pain.
These medications should be avoided in patients having ketoacidosis or are at risk of developing it (such as patients who are alcohol abusers, are on a restrictive diet, or have a pancreatic disease).
Renal Failure:
There is an increased risk of developing sudden kidney problems with the use of both canagliflozin and empagliflozin. These medications should be avoided in people with very low GFR.
Genital yeast infection and Fournier’s gangrene:
Increased risk of urinary tract infections and genital yeast infections. A serious life-threatening bacterial infection, Fournier’s gangrene, can also occur.
Patients should be evaluated right away if they experience any of the following symptoms: pain, tenderness, redness, or swelling in the genital or perianal area, fever, or malaise
Hypoglycemia:
People on insulin therapy are at a greater risk of hypoglycemia if SGLT2 inhibitors are also being administered. Careful dose adjustment is required to avoid sudden hypoglycemia.
Allergic reactions:
The medication should be immediately stopped if there is a risk of hypersensitivity or allergic reaction (swelling, breathing difficulties, etc.)
Dyslipidemia:
The levels of LDL cholesterol can also increase with the use of these medications.
However, Canagliflozin has some additional warnings
Canagliflozin comes with a boxed warning about lower limb amputation, which is the strongest warning required by the FDA (Food and Drug Administration).
Patients taking Canagliflozin were reported to be at a greater risk of lower limb amputation. According to reports, the major amputations involved the toe and midfoot but leg amputations were also observed.
Before starting treatment with canagliflozin, go for a careful assessment of the risk factors of lower limb amputations, and while using the medication, take extra care of the feet and look for any sores, pain, or ulcers.
Conclusion
Canagliflozin and Empagliflozin, both drugs, belong to the class of SGLT2 inhibitors. Both drugs are used in the treatment of type 2 diabetes mellitus and Heart failure.
Canagliflozin is also used in patients with End-stage kidney disease. Both drugs have the same effect, but some studies have reported that canagliflozin is better at reducing HbA1c levels as compared to empagliflozin.
However, canagliflozin also has a higher ratio of side effects as compared to empagliflozin.
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