In the latest draft guidance, the National Institute for Health and Care Excellence (NICE) has recommended dapagliflozin (marketed as Forxiga) to be used as triple therapy along with metformin and sulfonylurea in patients with type 2 diabetes who have inadequately controlled blood sugar (hyperglycemia).
Dapagliflozin is a selective sodium glucose cotransporter 2 (SGLT-2) inhibitor which blocks reabsorption of excess glucose by the kidneys so it can be excreted in the urine. SGLT-2 inhibitors also lower blood pressure and aid in weight loss.
This is rather important, given the linkage between type 2 diabetes and obesity. Some antidiabetic treatments, such as insulin and insulin secretagogues (sulfonylureas) such as tolbutamide, glipizide, and chlorpropamide etc, can also result in substantial weight gain in patients.
Around 3 million people in the UK have type 2 diabetes, most of whom are markedly obese. Diabetes is one of the most challenging conditions which still has no cure but can be managed with effective lifestyle changes and medications.
The first-line of therapy in patients with type 2 diabetes is diet and exercise. If neither works, metformin (a biguanide) is started. Despite therapy, only about 37.4% of people meet the targets recommended to reduce diabetes and diabetes related complications – a fact that has given rise to concern and prompted researchers to work on the new class(es) of antidiabetic medications.
Carole Longson, director of the NICE Center for Health Technology Evaluation, says, “Tailoring treatments for type 2 diabetes to each person’s individual needs is essential, and having a range of drug options makes this easier.”
Dapagliflozin is already used as a monotherapy when a combination of drugs is not recommended. Its usefulness as a dual therapy has also been established. A recent trial has found that when used in combination with exenatide, dapagliflozin was superior to metformin monotherapy in controlling blood sugar (HbA1C) and lowering risk of cardiac disease in patients with type 2 diabetes. Dual therapy also exhibited a clear superiority over monotherapy with either drug.
Dapagliflozin is used as both injectable and oral drug. It is used in doses of 10mg and costs around £475. The drug was approved by the US Food and Drug Administration (FDA) in 2014. Together with other gliflozins, the drug successfully prevents glucose co-transporter protein that is responsible for 90% reabsorption of glucose from kidneys back into the blood.
In the draft, the NICE said that it has fast-tracked appraisal of dapagliflozin so that the guidelines could be published sooner to benefit people with a new and equally effective treatment option.
Moreover, there is no differences in cost and effectiveness between the SGLT-2 inhibitors. Experts say that doctors can and should prescribe drugs to patients which are suit them more.
What Does This New Recommendation Add To Earlier Recommendations?
Earlier in May this year, NICE recommended dapagliflozin, canagliflozin (Invokana) and empagliflozin (Jardiance) as a monotherapy for patients who either cannot tolerate or are contraindicated to metformin, sulfonylurea or pioglitazone.
Although metformin is one of the most benign and effective drugs and used as first-line therapy for type 2 diabetes, it may stir adverse effects in a handful of patients – those who have a renal disease or experience excessive nausea and vomiting with the drug.
As per NICE, gliflozins are also an effective alternative to the latest class of antidiabetic drugs – called dipeptidyl peptidase-4 (DPP-4) inhibitors – which are instituted when neither diet and exercise nor monotherapy (metformin, pioglitazone or sulfonylureas) works.
DPP-4 inhibitors are anti-hyperglycemic agents which inhibit the degradation of two incretins, glucagon-like peptide-1 (GLP-1) and glucose dependent insulinotropic peptide (GIP). Incretins are related to greater amount of insulin secretion suggesting that inhibiting the degradation of incretins induces greater regulation of glucose by the body.
SGLT-2 inhibitors have an edge over DPP-4 inhibitors in that they have more glycemic control and weight reducing effects by prohibiting the reabsorption of glucose in the blood while DPP-4 inhibit glucagon release thus increasing insulin production and decreasing gastric emptying and blood sugar levels.
SGLT-2 inhibitors also offer better glucose control by increasing insulin sensitivity, uptake of glucose in the body’s tissues and improved first phase insulin release from the beta cells.
The new recommendation suggests that instead of switching therapy, the doctors in UK start prescribing a triple therapy – metformin plus sulfonylurea plus dapagliflozin.
The new recommendation from NICE will provide more treatment options to patients with type 2 diabetes particularly those who are reluctant or burdened with injecting insulin multiple times a day.
Diabetes is an ongoing condition and requires a lifelong management. Neglecting the condition can result in complications which include blindness, renal failure, heart disease and stroke.