COVID-19 and SGLT2 inhibitors: what’s the risk and how to manage it?

A primary care review of how to manage patients on SGLT2 inhibitors in the coronavirus pandemic.

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Introduction and background

Cotransporter-2 Inhibitors (SGLT-2i) are used in the treatment of diabetes and work by acting on the convoluted tubules of the kidney to prevent reabsorption of glucose. This results in higher levels of glucose being excreted in the urine and hence an improvement in diabetic control.

Clinically available SGLT2 inhibitors, canagliflozin, dapagliflozin, empagliflozin, and ertugliflozin can be used as monotherapy as well as combination therapy in the treatment of diabetes.

The class of medications have been shown to result in positive effects on other areas such as the cardiovascular system, with patients showing weight loss, decreasing blood pressure, preserving renal function, reduction in triglycerides, natriuresis and improved endothelial dysfunction.1 Trial evidence has confirmed this. The EMPA-REG OUTCOME trial with empagliflozin reported that patients with type 2 diabetes and high CV risk who received empagliflozin as add-on therapy to standard-of-care drugs as compared to placebo showed a lower rate of occurrence of primary CV outcomes and overall mortality.2

The Canagliflozin Cardiovascular Assessment (CANVAS) Study looked at patients who had a prior history of cardiovascular disease (CV) or at least 2 risk factors for CV disease by studying canagliflozin in more than 10,000 patients with type 2 diabetes. Study results showed that canagliflozin reduced the CV and nonfatal myocardial infarction (26.9 vs. 31.5%) and also demonstrated potential renal protective effects. However, there was an increase in risk of amputation.3

Side effects

Due to the increase in glucose excretion in the urine, side effects such as an increased risk of genital mycotic infections has been seen. Some patients have also had episodes of diabetic ketoacidosis (DKA) due to the reduced availability of carbohydrates thought to be as a result of the glycosuria, a shift in the utilisation of substrate to fat oxidation from glucose and promotion of hyperglucagonaemia. This has the effect of stimulating ketogenesis. Some patients also have symptoms of postural hypotension due to the volume depletion.1 This group of medication should be used with caution in patients who are high risk such as those taking diuretic medication.4

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References

  1. Pradhan A, Vohra S, Vishwakarma P, et al. Review on sodium-glucose cotransporter 2 inhibitor (SGLT2i) in diabetes mellitus and heart failure. J Family Med Prim Care. 2019 Jun;8(6):1855-1862.
  2. Saiz LC. The EMPA-REG OUTCOME trial (empagliflozin). A critical appraisal. The power of truth, the truth of power. DTB Navarre. 2016, 24. 1-13.
  3. Neal B, Perkovic V, Mahaffey KW, et al. Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes. N Engl J Med. 2017 Aug 17;377(7):644-657.
  4. Inagaki N, Kondo K, Yoshinari T, et al. Pharmacokinetic and pharmacodynamic profiles of canagliflozin in Japanese patients with type 2 diabetes mellitus and moderate renal impairment. Clin Drug Investig. 2014 Oct;34(10):731-42.

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