Dr. Ahmed
Xigduo XR is a two drugs combination pill. It contains two important diabetes medicines from two different classes, Dapagliflozin and Metformin.
Xigduo uses and indications include:
- Treat type 2 diabetes along with proper diet and exercise.
- To reduce the risk of heart failure in patients suffering from type 2 diabetes mellitus.
When used in the treatment of patients with heart failure, Xigduo is only recommended in patients with stable heart failure. Metformin can result in life-threatening lactic acidosis causing rapid cardiac decompensation.
Dapagliflozin MOA:
Dapagliflozin is a drug that works in the kidneys to block glucose absorption. This lowers blood sugar levels. Along with glucose excretion, it also results in the loss of water from the body.
Metformin MOA:
Metformin helps lower blood sugar levels by reducing sugar absorption from the gastrointestinal tract and the release of sugar by the liver (Glycogenolysis). Metformin also enhances the tissue’s response to insulin, reducing insulin resistance.
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Xigduo XR Use in Type 1 Diabetes:
It is important to note that the combination pill Xigduo is not indicated for the treatment of patients with Diabetes Mellitus Type 1.
Dapagliflozin monotherapy, Farxiga, was approved by the EMA for the treatment of Diabetes mellitus type 1 in certain situations.
These may include obese children with a BMI of 27 kg/m² or more, low risk of Diabetic ketoacidosis, and patients requiring high doses of insulin.
However, recently, the Farxiga indication in Diabetes Type 1 has been removed by the manufacturer. [Farxiga for Type 1 Diabetes Mellitus]
The primary indication of Xigduo (dapagliflozin and metformin) is T2DM. However, it is also used to lower the chance of heart failure in adults with type 2 diabetes mellitus, and those who have already been diagnosed with cardiovascular disease (CVD), or multiple cardiovascular risk factors.
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Other off-label uses of dapagliflozin and metformin include:
- Treatment of obesity in patients who have prediabetes
- Treatment of Fatty liver and NASH (Non-alcoholic steatohepatitis) in patients with Diabetes or Pre-diabetes.
- Treatment of Polycystic Ovarian Syndrome in females who have obesity and either diabetes or pre-diabetes.
Strengths of Xigduo XR (Dapagliflozin and Metformin) available:
- Only two strengths of Xigduo are available:
- Xigduo 5/850 mg (contains 5 mg dapagliflozin and 850 mg metformin), and
- Xigduo 5/1000 mg (contains 5 mg dapagliflozin and 1000 mg metformin).
How does Xigduo (dapagliflozin and metformin) work?
Dapagliflozin is from the class of medicines called SGLT2 inhibitors. It has a novel mechanism of action.
It inhibits SGLT2 receptors present in the proximal nephron of the kidney and blocks glucose reabsorption, causing glucose excretion via urine.
Because SGLT2 inhibitors are independent of insulin action, there is less risk for hypoglycemia.
Furthermore, they may be used at any stage in the progression of the disease. In addition, it causes the loss of glucose and salt from the body, it also induces weight loss, and has blood-pressure-lowering effects.
Metformin is a time-tested medicine from the class of drugs called, biguanides. It suppresses liver glucose production by inhibiting gluconeogenesis. It also improves insulin sensitivity and inhibits glucose absorption from the GI tract.
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How effective is Xigduo XR (Dapagliflozin and Metformin) in the Treatment of T2DM?
Xigduo treatment is usually initiated at a dose of 5 mg/1000 mg. The dose can be titrated to the maximum dose of 10 mg/2000 mg if required.
The efficacy of Xigduo treatment has been studied in different clinical trials. A 24-week study was carried out in patients who had uncontrolled diabetes with metformin.
Participants either received a placebo medicine or dapagliflozin 5 mg added to metformin, or dapagliflozin 10 mg added to metformin [Ref].
Significant reductions in the A1C were demonstrated, as mentioned below (P<0.0001):
- The placebo + metformin group had an A1C reduction of 0.3%
- Dapagliflozin 5 mg added to metformin had an A1C reduction of 0.7%
- Dapagliflozin 10 mg added to metformin had an A1C reduction of 0.84%.
The mean weight loss that occurred in the dapagliflozin group was 2.9 kgs for 5 mg and 3 kgs for 10 mg vs 0.9 kgs in the placebo group.
Henry et al carried out two randomized clinical trials [Ref]:
In the first 24-week trial, the effects of dapagliflozin and extended-release metformin were studied in patients with uncontrolled blood sugars and a mean HbA1C of 9.2%.
patients received either metformin extended-release alone, dapagliflozin 5 mg alone, or dapagliflozin 5 mg plus extended-release metformin.
In the second study, patients had the same mean HbA1C of 9.2%. Patients received dapagliflozin 10 mg once daily in addition to extended-release metformin.
In both studies, Dapagliflozin plus metformin brought down the HbA1C more effectively than either dapagliflozin or metformin monotherapy.
HbA1C reduction was as mentioned in the table below:
- Metformin alone: -1.5%
- Dapagliflozin 10 mg: -1.4%
- Metformin and Dapagliflozin combination: -2.1%
Patients who received combination treatment with dapagliflozin 5 mg plus metformin lost 2.7kg compared to 1.3 kg in those patients who received monotherapy with metformin.
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In Conclusion:
Xigduo XR uses and indications primarily include T2DM. However, it has been proven to induce weight loss and diuresis.
Because of these effects, Xigduo is also used in the treatment of patients with heart failure, NASH, fatty liver, and Polycystic ovarian syndrome.
