What are Invokana and Farxiga?
Invokana (canagliflozin) and Farxiga (dapagliflozin) belong to the drug class sodium-glucose co-transporter-2 (SGLT2) inhibitors. The FDA approved Invokana in March 2013 and Farxiga was approved in January 2014. They are both indicated for blood glucose (sugar) control in patients who have type 2 diabetes and should be combined with a healthy diet and exercise. These medications decrease blood glucose in people with diabetes by blocking the kidney from reabsorbing glucose and removing excess glucose through the urine. They do this by blocking the sodium-glucose co-transporter-2 (SGLT2), which is an enzyme (protein) in the kidney that is responsible for reabsorbing glucose back into the body. Lowering high blood glucose can help prevent nerve problems, blindness, and kidney damage in people with diabetes
Evidence from clinical studies has shown a reduction in body weight among diabetic patients. However, Invokana and Farxiga are not approved for the management of weight loss or obesity. It is important to understand the risks and benefits before considering their use in weight loss.
How does Invokana and Farxiga Cause Weight Loss?
Invokana and Farxiga increase urinary glucose excretion (UGE) by inhibiting SGLT2. This results in the removal of excess glucose calories every day, ultimately leading to weight loss. Subjects in an Invokana trial showed a UGE of 80 to 100 grams per day which is equivalent to 400 kilocalories (kcal) per day.
Invokana Studies on Weight Management in Diabetic Patients
- In several clinical studies, weight loss was assessed as a secondary endpoint during the 26-week or 52-week periods.
- The pattern of weight loss with Invokana was generally consistent across studies, with a reduction seen by week 12, and with continued weight loss over the 26-week or 52-week periods.
- Across these 3 studies, a greater body weight reduction was seen with Invokana 300 mg compared to Invokana 100 mg.
Change in Weight (kg) From Baseline in Invokana Studies
Invokana Studies on Weight Management in Non-Diabetic Patients
- An unpublished clinical study evaluated the safety and effectiveness of Invokana 50 mg, 100 mg, and 300 mg given once daily for 12 weeks on weight reduction in overweight or obese non-diabetic patients. However, the results of this study have not been published.
Farxiga Studies on Weight Management in Diabetic Patients
- A phase 3 study evaluated the change in total body weight (TBW) as a primary endpoint. Patients treated with Farxiga 10 mg added to metformin showed greater 24 and 102-week reductions in TBW compared to patients treated with placebo added to metformin (-2.96 kg compared to -0.88 kg at week 24 and -4.54 kg versus-2.12 kg at week 102).
- Weight loss was assessed as a secondary endpoint in 7 placebo-controlled studies and the results are shown in the table below.
Change in Weight (kg) From Farxiga Studies
Farxiga Studies on Weight Management in Non-Diabetic Patients
- Currently, there are no clinical studies evaluating Farxiga’s effect on body weight in non-diabetic patients.
What are the Side Effects of Invokana and Farxiga?
- Frequent urination
- Fungal infections especially in women
- Urinary tract infections
- Low blood glucose (if taken with another diabetes medication)
- Kidney problems
- Increase in cholesterol
- Low blood pressure
- Hyperkalemia: Increase in blood potassium levels (Invokana)
- Bladder cancer (Farxiga)
Average Wholesale Price (AWP) for Invokana and Farxiga
Invokana: $11.57 per tablet.
Farxiga: $11.57 per tablet
Weighing the Risks and Benefits of Invokana and Farxiga
Invokana and Farxiga have been associated with some favorable effects such as improved glycemic control in patients with type 2 diabetes, weight loss, and lower blood pressure. However, they are also associated with an increase in cholesterol, infections, hyperkalemia, and bladder cancer. Although these medications show evidence of moderate weight reduction, they are not approved for the management of obesity or weight loss. More studies with a longer duration of observation are needed to understand the risks and benefits of Invokana and Farxiga. Those looking for weight loss solutions should to talk with thier health care provider about the possible risks and benefits and established treatments for weight loss.
Bristol-Myers Squibb Medical Information (Personal Communication)
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Stenlöf K, Cefalu WT, Kim K-A, et al. Efficacy and safety of canagliflozin monotherapy in subjects with type 2 diabetes mellitus inadequately controlled with diet and exercise. Diabetes, Obesity and Metabolism. 2013;15:372-382.
Lavalle-Gonzalez FJ, Januszewicz A, Davidson J. Efficacy and safety of canagliflozin compared with placebo and sitagliptin in patients with type 2 diabetes on background metformin monotherapy: a randomized trial. Diabetologia. 2013 Dec;56(12):2582-92.
Wilding J, Mathieu C, Vercruysse F, et al. Canagliflozin, a sodium glucose co-transporter 2 inhibitor, improves glycemic control and reduces body weight in subjects with type 2 diabetes inadequately controlled with metformin and sulfonylurea. Poster presented at: The 72nd Annual Scientific Sessions of the American Diabetes Association (ADA), June 8-12, 2012, Philadelphia, PA.
Forst T, Guthrie R, Goldenberg R, et al. Efficacy and safety of canagliflozin in subjects with type 2 diabetes on metformin and pioglitazone. Poster presented at: The 4th World Congress on Controversies to Consensus in Diabetes, Obesity and Hypertension (CODHy), November 8-11, 2012, Barcelona, Spain.
Bolinder J, Ljunggren O, Kullberg J, et al. Effects of dapagliflozin on body weight, total fat mass, and regional adipose tissue distribution in patients with type 2 diabetes mellitus with inadequate glycemic control on metformin. J Clin Endocrinol Metab. 2012;97:1020-1031.
Bolinder J, Ljunggren Ö, Johansson L, et al. Dapagliflozin produces long-term reductions in body weight, waist circumference and total fat mass in patients with type 2 diabetes inadequately controlled on metformin [Poster 751]. Poster presented at: the 48th EASD Annual Meeting; October 1-5, 2012; Berlin, Germany.
Bolinder J, Ljunggren O, Johansson L et al. Dapagliflozin maintains glycemic control while reducing weight and body fat mass over 2 years in patients with type 2 diabetes mellitus inadequately controlled on metformin. Diabetes Obes Metab. 2013. Article first published online: 29 AUG 2013. DOI:10.1111/dom.12189.
Ferrannini E, Ramos SJ, Salsali A, et al. Dapagliflozin monotherapy in type 2 diabetic patients with inadequate glycemic control by diet and exercise: a randomized, double-blind, placebo-controlled, phase 3 trial. Diabetes Care. 2010;33(10):2217-2224.
Bailey CJ, Iqbal N, T’joen C, List JF. Dapagliflozin monotherapy in drug-naive patients with diabetes: a randomized-controlled trial of low-dose range. Diabetes Obes Metab. 2012;14(10):951-959.
Bailey CJ, Gross JL, Pieters A, et al. Effect of dapagliflozin in patients with type 2 diabetes who have inadequate glycemic control with metformin: a randomized, double-blind, placebo-controlled trial. Lancet. 2010;375(9733):2223-2233.
Wilding JP, Woo V, Soler NG, et al. Long-term efficacy of dapagliflozin in patients with type 2 diabetes mellitus receiving high doses of insulin. Ann Intern Med. 2012;156(6):405–415.
Strojek K, Yoon KH, Hruba V, et al. Effect of dapagliflozin in patients with type 2 diabetes who have inadequate glycemic control with glimepiride: a randomized, 24-week, double-blind, placebo-controlled trial. Diabetes Obes Metab. 2011;13(10):928-938.
Rosenstock J, Vico M, Wei L, et al. Effects of dapagliflozin, a sodium-glucose cotransporter-2 inhibitor, on hemoglobin A1c, body weight, and hypoglycemia risk in patients with type 2 diabetes inadequately controlled on pioglitazone monotherapy. Diabetes Care. 2012;35:1473-1478.
Jabbour SA, Hardy E, Sugg J, Parikh S. Dapagliflozin is effective as add-on therapy to sitagliptin with or without metformin: a randomized, double-blind, placebo-controlled study. Poster presented at: 72nd Annual Scientific Sessions of the American Diabetes Association; June 8-12, 2012; Philadelphia, PA; Poster 1071-P.