SGLT1 Inhibitors

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SGLT1 Inhibitors are new diabetes medications that delay and reduce the absorption of glucose in the small intestine. SGLT1 treatment could improve your diabetes control, significantly reducing blood sugars after eating.

What are SGLT1 and SGLT2 inhibitors?

With just one digit differentiating them, the names of these medications can seem confusing. However, SGLT1s and SGLT2s act on different essential proteins that help the body reabsorb glucose. We’ll go through where, when and how they function:

SGLT2 inhibitors include the medication dapagliflozin or Forxiga®. They are part of a group of diabetes medications that prevent the kidneys from reabsorbing glucose. As a result, more glucose is lost in the urine, and glucose levels in your blood will fall.

SGLT2 stands for sodium-glucose like co-transporter 2 inhibitors. Sodium-glucose like co-transporter 2, is a protein that helps the body reabsorb glucose in the kidney tubules. SGLT2 inhibitors block the action of this vital protein so that more glucose is forced into the urine and out of the body. SGLT2 proteins are responsible for about 90 – 95% of glucose reabsorbed in the kidneys.

SGLT1 inhibitors work on a different transport protein, sodium-glucose like co-transporter 1. Sodium-glucose-like co-transporter 1 also has important roles in the reabsorption of glucose. It has a more minor role in the kidneys, working further down in the tubules to reabsorb glucose. It’s responsible for 5% of glucose reabsorbed in the kidneys, about 10 grams per day. That doesn’t seem very much, but SGLT1s also work to reabsorb glucose in the small intestine. By blocking their action, you can reduce blood glucose and improve glycaemic control, particularly after meals.

Who can benefit from SGLT1 and SGLT2 inhibitors?

SGLT2 inhibitors are used in combination with insulin and other therapies to manage type 1 and type 2 diabetes. They are beneficial in improving diabetes control and protecting against diabetes-related complications. SGLT2s usually lead to some weight loss and also reduce blood pressure.

SGLT1 inhibitors are beneficial for patients with impaired renal function, where SGLT2 inhibitors are less effective. By delaying and reducing glucose absorption in the small bowel, they can reduce glucose spikes after eating and improve glycaemic control after meals.

At the time of writing this blog, in late 2021, no pure SGLT1 inhibitors were licensed for use in the UK. However, research trials are ongoing, so watch this space.

Dual SGLT1/SGLT2 inhibitors

Sotagliflozin, or Zinquista, is a drug that inhibits both SGLT1 and SGLT2, acting in the kidneys and the small bowel to prevent glucose reabsorption and lower blood glucose levels.

There is some research evidence that sotagliflozin can reduce the risk of cardiovascular deaths, hospitalisations, and urgent visits for heart failure in people with diabetes and chronic kidney disease.

In the UK, sotagliflozin is not generally available for prescription on the NHS. However, the National Institute for Health and Care Excellence (NICE) expects it to be available shortly. NICE published guidance recommending sotagliflozin for the treatment of adults with type 1 diabetes for individuals with a body-mass index (BMI) of at least 27 kg/m2 in whom insulin alone doesn’t adequately control their blood glucose. NICE said:

Sotagliflozin (one 200 mg tablet daily) is an option for some people who cannot manage their type 1 diabetes with insulin alone.’

‘Evidence from clinical trials run for one year in this population shows improvements in blood glucose (HbA1c) and weight loss, and improvements in quality of life, with sotagliflozin plus insulin compared with people on placebo plus insulin. The company assumes that the improvement in HbA1c results in a lower risk of long-term complications over a person’s lifetime. It’s reasonable to assume some relationship between lowering HbA1c and reducing diabetic complications, and between lowering BMI and improving quality of life.

Sotagliflozin is also in clinical development for the treatment of type 2 diabetes.

Sotagliflozin side effects

All medications can cause side effects. Safe and effective treatment is about balancing the benefits of the drug with the potential risks and complications. Sotagliflozin can cause side effects and complications, including:

  • Diarrhoea and GI disturbance
  • Thrush and genital fungal infections
  • Urinary tract infections
  • Dehydration
  • Low blood pressure, particularly in the elderly
  • Diabetic ketoacidosis: DKA was more common in people taking sotagliflozin than those taking a placebo. As a result, it should be avoided in people at increased risk of DKA; it’s also important to be aware of the signs and symptoms of DKA and seek urgent medical attention if you’re concerned

To find out more about diabetes treatment, or to speak to one of our specialists at The London Diabetes Centre about prospective treatment options, contact us today.

Sources:

https://www.io.nihr.ac.uk/report/sotagliflozin-for-type-2-diabetes-mellitus/

https://www.nejm.org/doi/full/10.1056/NEJMoa2030186

https://pubmed.ncbi.nlm.nih.gov/30132033/

https://www.nursingcenter.com/ncblog/november-2018/sglt2-and-sglt1

https://www.nice.org.uk/guidance/ta622

https://www.thelancet.com/journals/landia/article/PIIS2213-8587(20)30066-8/fulltext

https://www.ema.europa.eu/en/documents/product-information/zynquista-epar-product-information_en.pdf

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