e-learning | Ertugliflozin in type 2 diabetes and the other SGLT-2 inhibitors

This is a new guideline from NICE giving advice on ertugliflozin, published in April 2019. I am also doing a quick reminder about the other SGLT-2 inhibitors.

What is ertugliflozin?

It is another sodium-glucose co-transporter 2 (SGLT-2) inhibitor, like canagliflozin, dapagliflozin and empagliflozin.

It is thought to be as effective as the other SGLT-2 inhibitors, but it is cheaper.

The SGLT-2 inhibitors work by blocking reabsorption of glucose in the kidneys. This leads to more glucose being excreted and less staying in the blood.

When can it be used?

Monotherapy.

It can be used if all the following conditions are met:

  • Adults with type 2 diabetes AND
  • Where metformin is contraindicated or not tolerated AND
  • When diet and lifestyle modification alone don't give adequate glycaemic control AND
  • If otherwise a dipeptidyl peptidase 4 (DPP-4) inhibitor would be used AND
  • A sulfonylurea or pioglitazone is not appropriate.

Dual-therapy.

It can be used in combination with metformin IF:

  • a sulfonylurea is contraindicated or not tolerated OR
  • the patient is at significant risk of hypoglycaemia or its consequences.

Triple-therapy.

The linked guidance above on ertugliflozin doesn't state that it can be used in triple therapy. However the NICE pathway on type 2 diabetes advises that it can be used in triple therapy in combination with metformin and a DDP-4 inhibitor if:

  • their diabetes is not controlled by the combination of metformin + a DDP-4 inhibitor AND if
  • a sulfonylurea or pioglitazone is not appropriate.

So what about the other SGLT-2 inhibitors?

For monotherapy and dual-therapy, the indications are the same for all of the SGLT-2 inhibitors. For triple therapy, there is a bit of difference between them.

SGLT-2 inhibitors used as monotherapy.

The indications are the same for all of them. They can be used in:

  • Adults with type 2 diabetes AND
  • Where metformin is contraindicated or not tolerated AND
  • When diet and lifestyle modification alone don't give adequate glycaemic control AND
  • If otherwise a dipeptidyl peptidase 4 (DPP-4) inhibitor would be used AND
  • A sulfonylurea or pioglitazone is not appropriate.

The NICE guidance on the use of dapagliflozin, empagliflozin and canagliflozin as monotherapy can be found here.

SGLT-2 inhibitors used as dual-therapy.

The indications are the same for all of them. They can be used in combination with metformin IF:

  • a sulfonylurea is contraindicated or not tolerated OR
  • the patient is at significant risk of hypoglycaemia or its consequences.

SGLT-2 inhibitors used in triple therapy.

Dapagliflozin - can be used in combination with metformin and a sulfonylurea.

Canagliflozin and empagliflozin - can be used either:

  • In combination with metformin and a sulfonylurea OR
  • In combination with metformin and a thiazolidinedione

Ertugliflozin - can be used in combination with metformin and a DDP-4 inhibitor (if a sulfonylurea or pioglitazone is not appropriate).

The NICE guidance on the use of dapagliflozin in combination therapy can be found here.

The NICE guidance on the use of empagliflozin in combination therapy can be found here.

The NICE guidance on the use of canagliflozin in combination therapy can be found here.

Is there anything important to remember about the use of SGLT-2 inhibitors?

Ketoacidosis - there is a risk of ketoacidosis with the use of SGLT-2 inhibitors. This risk can continue for a short while after they are stopped. Because the glucose gets excreted in the urine, the glucose levels can be normal, even though the ketone levels are high. Most cases of this have been seen in type 1 diabetics, but it can happen in type 2 diabetics too.

Canagliflozin and lower limb amputation. There is an increased risk of lower limb amputation with canagliflozin. This mainly affects the toes. There has been no increased risk shown with the other SGLT-2 inhibitors at present, but it is possible that it is a class effect.

Want a good reminder of what drugs to use in type 2 diabetes?

NICE has an excellent A4 summary of what medications to use in type 2 diabetes. As I publish this, it hasn't been updated to show ertugliflozin, but hopefully it will be updated soon.

I have previously done a blog post on the NICE guideline on type 2 diabetes, if you want a general overview of management.

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