Over 29 million Americans have type 1 or type 2 diabetes (T2D). With all the medications that are on the market currently for the treatment of diabetes, many patients still appear to need better glycemic control.  Recently, empagliflozin (Jardiance, Boehringer Ingelheim Pharmaceuticals) won approval from the FDA.  Empagliflozin can be prescribed by itself or as an adjunct to other medications for T2D. The medication is not indicated for patients with type 1 diabetes, diabetic ketoacidosis, severe renal impairment, or end-stage renal disease or for patients receiving dialysis.

Empagliflozin is the third oral sodium glucose cotransporter 2 (SGLT2) to receive FDA approval, joining canagliflozin (Invokana, Janssen Pharmaceuticals) and dapagliflozin (Farxiga, AstraZeneca/BMS). SGLT2 products are indicated for improving glycemic control in adults with type 2 diabetes in conjunction with diet and exercise. Empagliflozin like other SGLT2 medications lowers plasma glucose levels by increasing the amount of glucose excreted in urine and removes excess glucose through the urine by blocking glucose re-absorption in the kidney.

Findings of empagliflozin seen in 7 clinical trials (4500 patients) were as follows:

  • Lower hemoglobin A1c (A1C) compared to placebo
  • Common adverse effect: urinary tract infections and female genital infections  

Empagliflozin was not compared head to head with other SGLT2 medication products so it is difficult to predict how significant the effect on glycemic control will be compared with other agents from the same class. What is unique about this product is the ongoing efforts to market this product with a dipeptidyl peptidase-4 (DPP-4) inhibitor, linagliptpin (Tradjenta). DPP-4 inhibitors work by increasing hormones that stimulate the pancreas to produce more insulin and stimulate the liver to produce less glucose.

Two 52-week phase 3 trials compared the combination of empagliflozin and linagliptin with empagliflozin or linagliptin alone in patients with T2D with mean A1C of 8% at baseline.

The first 52-week study of 686 randomized adults, who were taking metformin, examined the change from baseline of A1C at 24 weeks using empagliflozin 25 mg/linagliptin 5 mg, and empagliflozin 10 mg/linagliptin 5 mg dose combinations:

•    Both empagliflozin/linagliptin combination doses showed statistically significant reductions in A1C vs. the component doses of empagliflozin or linagliptin alone.

•    Statistically significantly more adults who had A1C >7.0%  at baseline achieved A1C <7.0% after 24 weeks with both dose combinations versus either empagliflozin or linagliptin alone.

•    The empagliflozin/linagliptin combinations resulted in weight loss similar to that of empagliflozin monotherapy.

•    Safety data of the combination tablet was similar to the safety data of the individual components
The second 52-week Phase 3 study of 677 adults who were treatment-naïve examined the reduction in A1C from baseline at 24 weeks.

•    A1C reduction with the empagliflozin 10 mg/linagliptin 5 mg combination was significantly greater than that of empagliflozin 10 mg alone but not greater than empagliflozin 25mg.

•    Significantly more adults who had A1C >7.0%  at baseline achieved A1C levels  < 7.0 % after 24 weeks with both doses of the empagliflozin/linagliptin combination versus the empagliflozin component dose or linagliptin alone

•    Compared with linagliptin 5 mg, both combination doses significantly reduced A1C and body weight.

•    Safety data of the combination tablet was similar to the safety data of the individual components

I am encouraged by the reductions in blood glucose levels with the empagliflozin/linagliptin combination tablet. People with type 2 diabetes must often take more than one medication to adequately control their blood glucose levels. The pill burden is often seen as a barrier to proper compliance with medication therapy. The approval of empagliflozin is the first step to getting this potential combination product approved. 

If approved, the empagliflozin/linagliptin tablet will be the first time that two mechanisms of action, an SGLT-2 and a DPP-4 inhibitor, in a single pill will be available. That combination pill could be an important treatment option for physicians and patients and improve compliance with medication regimen.