Dr Aidin Rawshani

An additional SGLT-2 inhibitor reduces morbidity and mortality in type 2 diabetes


SGLT-2 inhibitors: a new generation of drugs for type 1 and type 2 diabetes

SGLT-2 inhibitors are a new type of drug that took the world by storm when the EMPA-REG study was published in 2015. It can be safely said that very few researchers expected that the drug empagliflozin (which is an SGLT 2 inhibitor) would have a major impact on morbidity and mortality in type 2 diabetes. Empagliflozin, which is, therefore, an SGLT 2 inhibitor, has a fairly simple mechanism of action and it takes place in the kidneys. Our kidneys have the task of purifying the blood of waste products and waste substances. Once the kidneys filter the blood, urine remains as we pee out. The kidneys filter blood in several batches and during filtration, sugar (glucose) is in the urine; but the kidneys know that the body needs glucose and therefore has enzymes that retrieve sugar (glucose) in the urine so that it is returned to the bloodstream. Empagliflozin prevents these enzymes from functioning normally, which means that they are not able to take back as much sugar and that makes us pee out more sugar.

So far we are sure of the effects of empagliflozin, but when EMPA-REG was published, the researchers were very surprising because the study showed that empagliflozin reduced the risk of death, cardiovascular disease and heart failure – the effect was very pronounced. The effect can actually be compared with statins and ACE inhibitors (the most common and best type of antihypertensive drug). Here is a picture illustrating the difference in efficacy between these three drugs. The picture shows NNT (Number Needed to Treat), which is a number that indicates how many people need to be treated to save the life of a person.

Effekten av SGLT-2-hämmaren empagliflozin, jämfört med statiner och ACE-hämmare. Denna bilden visar hur många människor som måste behandlas för att förhindra ett dödsfall. Som vi ser måste 56 personer behandlas med ramipril (ACE-hämmare som sänker blodtryck har har både njur- och hjärtskyddande effekt) under 5 år för att rädda ett liv. För statiner måste 30 personer behandlas under 5.4 år för att förhindra ett dödsfall. För Empagliflozin är siffran 39 personer under 3 år, vilket är imponerande siffror, särskilt när man beaktar att empagliflozin utforskades under en period då allra flesta patienter fick både ACE-hämmare och statiner.
The effect of the SGLT-2 inhibitor empagliflozin, compared with statins and ACE inhibitors. This picture shows how many people need to be treated to prevent death. As we see, 56 people need to be treated with ramipril (ACE inhibitors that lower blood pressure has both renal and cardioprotective effects) for 5 years in order to save a life. For statins, 30 people must be treated under 5.4 years of age to prevent one death. For Empagliflozine, the figure is 39 people under 3 years of age, which is impressive figures, especially when considering that empagliflozin was explored during a period when the vast majority of patients received both ACE inhibitors and statins.

As you can see, empagliflozin is almost as effective as statins, and more effectively than ACE inhibitors. This is very revolutionary and therefore no wonder that the scientific community (at least the one involved in diabetes and cardiovascular diseases) was very surprised by the results. It has therefore been expected that competitors of empagliflozin would complete their studies (because there are more companies producing SGLT 2 inhibitors). Now another drug has been published (that study is called CANVA) and the results are consistent with the previous study.


CANVAS studied how canagliflozin, an SGLT 2 inhibitor, affects morbidity and mortality among people with type 2 diabetes. It was previously known that SGLT 2 inhibitors have a good effect on long-term blood sugar, blood pressure, weight, and kidney damage (both canagliflozin and empagliflozin had shown this). CAVAK included 10142 patients with type 2 diabetes and a high risk of cardiovascular disease. Half of the participants received a placebo (idle sugar pill) and the other half received canagliflozin. These participants were followed for about 3.5 years. The big question was whether canagliflozin could reduce the risk of cardiovascular disease (heart attack, stroke) or death as a result of cardiovascular disease.


Here we see the effects of canagliflozin, compared to placebo, on long-term blood sugar (HbA1c), weight, systolic blood pressure, and diastolic blood pressure.

Here we see the effects of canagliflozin, compared to placebo, on mortality, cardiovascular disease, and kidney disease.


  • The risk of cardiovascular disease or death due to cardiovascular disease was 14% lower for those receiving canagliflozin.
  • There was a tendency for canagliflozin to have a renal protective effect, as the risk of worsening kidney damage was 27% lower among those receiving canagliflozin. However, this difference was not statistically assured.
  • Amputations were twice as common among those receiving canagliflozin (6.3 patients per 1000 were amputated in the canagliflozin group, compared with 3.4 patients with 1000 in the placebo group). Amputations, as a rule, were on the toes and metatarsal bones.


CANVA reduces the risk of cardiovascular disease and death as a result of cardiovascular disease, at the expense of increased risk of amputations of toes and metatarsal bones.

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