SGL2 Inhibitors in 2020

Dr KK Aggarwal

President CMAAO and HCFI

In 2020, the American Diabetes Association is making two paradigm-shifting recommendations in the treatment of type 2 diabetes.

1.      Prescribe Sodium glucose co-transporter 2 (SGLT2) inhibitors or glucagon-like peptide 1 (GLP-1) receptor agonists to patients at high risk for atherosclerotic cardiovascular disease, heart failure, or chronic kidney disease, in addition to patients with already established disease, as previously recommended.

2.      Consideration for use of those drugs be independent of the patient's baseline A1c or individualized A1c target. Previously, additional pharmacologic agents were recommended only when A1c was above target despite using first-line metformin and lifestyle interventions.

Atherosclerotic CV Disease: Add Empagliflozin

Heart Failure: Empagliflozin, canagliflozin or dapagliflozin. For patients with heart failure with reduced ejection fraction (HFrEF) who have persistent symptoms and an elevated serum natriuretic peptide level on optimal pharmacologic and device therapy, add dapagliflozin.

CKD:  Canagliflozin in patients with diabetes and proteinuria: In patients with type 2 diabetes who have nephropathy (urine albumin excretion >300 mg per day) and eGFR >30 mL/min per 1.73 m², add Canagliflozin (CREDENCE trial).

In addition, SGLT2 inhibitors in general may have a role as a third agent in those who cannot or will not take insulin, when full doses of metformin and a sulfonylurea have not produced satisfactory metabolic control, or in patients in whom risk of hypoglycaemia is high (frail, older adults) or in whom avoidance of weight gain is a priority. 

World Kidney Day: Same serum creatinine value may mean different eGFR for persons of different body weight

Serum creatinine is a commonly used test to evaluate kidney function. And, if the creatinine value falls within the lab reference range, then all is considered well. However, this is not so because the creatinine level is affected by age, race, gender and also the body weight. Hence, serum creatinine level alone is an unreliable marker for impaired kidney function or chronic kidney disease.

The GFR or glomerular filtration rate is the best measure to assess the function of the kidneys.

There are several ways to calculate the GFR.

The most common is Cockcroft Gault equation. It calculates creatinine clearance (mL/min) as a surrogate for GFR. It provides an estimate of GFR based on serum creatinine, age, gender and body weight. 

The formula is:

Estimated or eGFR = 140 – age x body weight (in kg)/72 × serum creatinine (in mg/dL)

·         A value of 60 or higher is normal (GFR decreases with age). 

·         A value less than 60 is low and may indicate kidney disease.

·         A value of 15 or lower may mean kidney failure.

The same serum creatinine value may mean different GFR for similarly aged persons of different body weight.

·         A 40 kg man, aged 40 years, with serum creatinine of 1, the GFR is 55.

·         A 50 kg man, aged 40 years, with serum creatinine of 1, the GFR is 69.

·         A 60 kg man, aged 40 years, with serum creatinine of 1, the GFR is 83.

·         A 70 kg man, aged 40 years, with serum creatinine of 1, the GFR is 97.

·         A 80 kg man, aged 40 years, with serum creatinine of 1, the GFR is 111.

If you are at increased risk for kidney disease i.e. if you have diabetes, high blood pressure, or family history of diabetes, high blood pressure or kidney disease, then calculate your GFR to know if you have kidney disease.

The GFR may show impaired kidney function, even if the serum creatinine level is in the normal range.

Another important point to take note of is that instead of looking at a single test result, one should look for trends in the results. 

Always compare the results of a particular test with previous reports even when a result is normal. Results that show change over time i.e. show a rising or declining trend by 0.3 are important and should not be ignored.

Any result which has been in the low normal range for the last many years, but is now in the high normal range even though still within normal limits, should be investigated accordingly.

Dr KK Aggarwal

Padma Shri Awardee

President Elect Confederation of Medical Associations in Asia and Oceania   (CMAAO)

Group Editor-in-Chief IJCP Publications

President Heart Care Foundation of India

Past National President IMA