One of my patients asked me "Is Anxiety a side effect of Jardiance?". I had heard about most of the side effects of Jardiance but I could not answer this question. After I reached home, I searched for studies, case reports, and review articles to answer this question. I am sharing all the articles that mention anxiety as a side effect of Jardiance (empagliflozin).

Before that, I would like to share my personal experience of Jardiance (empagliflozin).

I have been using Jardiance (empagliflozin) very frequently. I prefer prescribing Jardiance to diabetic patients with the following features:

• Obese patients with diabetes type 2.
• Patients who are intolerant to metformin or a combination of metformin and sitagliptin.
• Patients with a recent onset of diabetes
• Patients with mild to moderately uncontrolled diabetes type 2.
• Patients on maximum doses of metformin, sitagliptin/ vildagliptin, and/ or sulfonylureas and not willing to start insulin.
• Patients with a low risk of urinary tract infections.
• Patients with heart disease especially those with stable heart failure
• Patients with proteinuria
• Patients with hypertension.

Obese patients with mild to moderately uncontrolled diabetes are the ones who benefit from Jardiance the most. I have seen patients who have reversed diabetes with Jardiance (empagliflozin) and other SGLT 2 inhibitors like Dapagliflozin. Most of these patients lose weight and achieve their metabolic circadian rhythm resulting in the normalization of blood glucose without medicines. This is associated with a great improvement in the social well-being resulting in improvement in the symptoms of anxiety.

After discussing the positive aspects, I have also seen patients who experienced some of the serious side effects of this drug.

One of my female patients developed severe urinary tract infection that was resistant to most oral antibiotics. The patient was admitted and received amikacin and improved. After a few days, she again relapsed with the same infection, even though, Jardiance (empagliflozin) was stopped. Urinary tract infections have been the most common adverse drug effects in my clinical practice. Another patient noticed a rise in creatinine that improved with hydration and stopping the drug. The patient who asked me this question "Is anxiety a side effect of Jardiance?" had a weird kind of experience with Jardiance (empagliflozin). He reported heart sinking, palpitations, headache, tinnitus, irritability, vertigo, restlessness, disturbed sleep, excessive anger, and worries when he took a single dose. The same symptoms repeated again when he took the dose. He reduced the dose to half but his symptoms would recur. Surprisingly, he was switched to low dose dapagliflozin 5 mg and he tolerated the drug very well.

Are there any studies that have reported anxiety as a side effect of Jardiance?

In one study, about 18% of the patients reported symptoms of anxiety with empagliflozin 10 and 25 mg. However, a comparable proportion of patients in the placebo group reported having anxiousness. Another study showed an improvement in the quality of life with its use. This could be a result of better glycemic control. A study titled "Sodium-glucose cotransporter 2 inhibition as a potential treatment for idiopathic edema" hypothesized that SGLT 2 inhibition reduces the adrenergic output resulting in an improvement in anxiety. It is also important that Jardiance may result in euglycemic ketoacidosis. Euglycemic ketoacidosis may manifest with non-specific symptoms like abdominal pain, anxiety, delirium, altered mentation, and confusional states. A meta-analysis titled "Efficacy and safety of sodium-glucose cotransporter 2 inhibitors as an add-on to metformin and sulfonylurea treatment for the management of type 2 diabetes: a meta-analysis" noted that hypoglycemia resulting from the addition of SGLT 2 inhibitors cause anxiety in the patients.

Adrenergic symptoms or neuroglycopenic symptoms are two ways that hypoglycemia might present.

Adrenergic symptoms include:

• sweating
• anxiety
• Palpitations
• elevated blood pressure
• insomnia
• irritability

Neuroglycopenic symptoms include:

• Loss of concentration
• drowsiness
• weakness
• confusion
• blurring of vision
• coma

The Final words ...

All the studies do not reveal any direct association of Jardiance with anxiety. Patients who have better control of diabetes may report improvement in the symptoms of anxiety. Those who develop hypoglycemia or hyperglycemia may develop symptoms of anxiety due to the poor control in patients with hyperglycemia and adrenergic symptoms in patients with hypoglycemia. Obese patients may report weight loss with Jardiance and hence report improvement in the symptoms of anxiety. Patients who develop ketoacidosis may present with anxiety and abdominal symptoms. Those who develop infections like urinary tract or genital mycotic infections may become anxious because of their illness.