A new class of oral hypoglycemic drugs - SGLT-2 inhibitors

Aug 17, 2021

SGLT-2 inhibitors, sodium-glucose cotransporter 2 inhibitors, are a new class of oral hypoglycemic drugs. This kind of drugs include empagliflozin(CAS No.:

864070-44-0), dapagliflozin(CAS No.: 864070-37-1) and canagliflozin (CAS No.: 842133-18-0). The latest research proves that in addition to lowering blood sugar, SGLT2 inhibitors also have unique effects such as lowering blood pressure and improving the prognosis of the heart and kidneys.

1. Unique hypoglycemic mechanism

Under normal circumstances, the daily glomerular filtered glucose is about 180g/d, but 100% of this glucose is reabsorbed by the sodium-glucose cotransporter (SGLT-1, SGLT-2) on the renal tubules.

SGLT-2 inhibitors, by inhibiting the reabsorption of glucose and sodium ions by SGLT-2, can excrete 70-80g/d glucose from the urine, thereby exerting a hypoglycemic effect and a hypotensive effect.

It should be noted that due to the increase of glucose concentration in urine, SGLT2 inhibitors can increase the risk of urinary and reproductive tract infections. Patients should increase their drinking water, keep the vulva clean, and give treatment if necessary.

2. SGLT-2 inhibitor's anti-diabetic effect

(1) Lose weight

SGLT-2 inhibitors increase urine excretion of glucose by 70-80g/d, which is equivalent to 300kcal of calories, which is equivalent to eating less than 4~5 taels of rice, or taking 1~12,000 more steps. Continuous use of SGLT-2 inhibitors can reduce body weight by 1.5 to 3.5 kg.

Metformin (CAS No.: 1115-70-4) alone can reduce weight slightly, and combined use can reduce weight gain caused by sulfonylureas and insulin.

(2) Lower blood pressure

SGLT-2 inhibitors, namely sodium-glucose cotransporter 2 inhibitors, can inhibit glucose reabsorption and at the same time promote urinary sodium excretion, reduce plasma volume by about 7%, and can relax after 1 to 2 weeks of medication The blood pressure drops by 1~2mmHg, and the systolic blood pressure drops by 3~5mmHg.

Metformin has no antihypertensive effect.

(3) Heart protection

Enpagliflozin, canagliflozin and dapagliflozin, which have been on the market in China, have all been shown to have cardioprotective effects, which can significantly reduce the risk of major cardiovascular adverse events and the hospitalization rate for heart failure.

Compared with placebo, empagliflozin can reduce the risk of major cardiovascular adverse events (including cardiovascular mortality, non-fatal myocardial infarction, and non-fatal stroke) in diabetic patients by 14%, and reduce cardiovascular mortality The rate of hospitalization for congestive heart failure and the incidence of myocardial infarction decreased by 38%, 33%, and 13%, respectively.

UKPDS research shows that metformin can reduce the relative risk of all-cause death in overweight or obese newly diagnosed type 2 diabetes patients by 35% and the risk of myocardial infarction by 39%.

(4) Kidney protection

Enpagliflozin, canagliflozin and dapagliflozin that have been marketed in China all have renal protection (see the picture of mechanism of action).

Compared with placebo, canagliflozin can reduce the risk of composite endpoints (continuous creatinine doubling, ESRD, death due to kidney disease) by 47%, and the risk of albuminuria progression is reduced by 27%.

Metformin has no nephrotoxicity and has a neutral protective effect on the kidneys.

(5) Lower uric acid

SGLT-2 inhibitors can promote uric acid excretion, and both enpagliflozin and dapagliflozin can reduce blood uric acid by 40-50 μmol/L.

Metformin can improve insulin resistance, thereby reducing blood uric acid production and increasing uric acid excretion.

3. The choice of hypoglycemic drugs

(1) For type II diabetes, regardless of whether it is combined with atherosclerotic cardiovascular disease (ASCVD), metformin is still the drug of choice and should always be kept in the treatment plan.

(2) For type II diabetes with ASCVD, it is recommended to use SGLT2 inhibitors or glucagon-like peptide 1 receptor agonists (GLP-1RA) with cardiovascular benefits.

(3) For type II diabetes with heart failure or chronic kidney disease, SGLT2 inhibitors are preferred; for those with SGLT-2 contraindications or intolerance, GLP-1RA should be used.

(4) Metformin, SGLT-2 inhibitor, and GLP-1RA can be used in combination when blood glucose is not up to the target.

Tags : Metformin empagliflozin