From the Guidelines
Empagliflozin does not prevent fluid retention when given with pioglitazone in patients with Type 2 Diabetes Mellitus (T2DM), and in fact, the combination may increase the risk of heart failure due to pioglitazone's fluid-retaining properties. According to the 2019 ESC guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD 1, thiazolidinediones like pioglitazone are associated with an increased risk of incident heart failure in patients with diabetes, and are not recommended for diabetes treatment in patients at risk of heart failure. While empagliflozin, as an SGLT2 inhibitor, has a natural diuretic effect that can help reduce fluid retention, the combination with pioglitazone may not be beneficial in preventing fluid retention due to the latter's adverse effects on heart failure risk. Key considerations when using this combination include:
- Monitoring patients for signs of fluid status and heart failure
- Assessing individual patient factors such as renal function, cardiovascular status, and risk of genital infections
- Weighing the benefits of pioglitazone's insulin-sensitizing effects against the potential risks of fluid retention and heart failure exacerbation. The guidelines recommend SGLT2 inhibitors like empagliflozin to lower the risk of heart failure hospitalization in patients with diabetes, but advise against using thiazolidinediones like pioglitazone in patients at risk of heart failure 1.
From the FDA Drug Label
Empagliflozin pharmacokinetics were similar with and without coadministration of metformin, glimepiride, pioglitazone, sitagliptin, linagliptin, warfarin, verapamil, ramipril, and simvastatin in healthy volunteers and with or without coadministration of hydrochlorothiazide and torsemide in patients with type 2 diabetes mellitus
The FDA drug label does not answer the question.
From the Research
Empagliflozin and Pioglitazone in T2DM
- The combination of empagliflozin and pioglitazone in patients with Type 2 Diabetes Mellitus (T2DM) has been studied in several clinical trials 2, 3, 4, 5, 6.
- Empagliflozin, an SGLT2 inhibitor, has been shown to improve glycemic control, reduce body weight, and lower blood pressure without increasing the risk of hypoglycemia 2, 4, 6.
- Pioglitazone, a thiazolidinedione, has been shown to improve insulin sensitivity and reduce glucose levels, but it can cause fluid retention 5, 6.
Effect on Fluid Retention
- The study by 6 investigated the efficacy and tolerability of empagliflozin as add-on to pioglitazone ± metformin in patients with T2DM and found that empagliflozin improved glycemic and weight control without increasing fluid retention.
- Another study by 5 compared the effects of pioglitazone and empagliflozin on left ventricular function in patients with T2DM and nonalcoholic fatty liver disease and found that both treatments improved left ventricular mechanics, but empagliflozin ameliorated liver steatosis more effectively.
- However, none of the studies directly addressed the question of whether empagliflozin prevents fluid retention when given with pioglitazone in patients with T2DM.
Potential Benefits and Risks
- The combination of empagliflozin and pioglitazone may offer potential benefits in terms of improved glycemic control, weight loss, and cardiovascular risk reduction 2, 3, 6.
- However, the risks of fluid retention and other adverse events, such as urinary tract and genital infections, should be carefully monitored and managed 4, 5.