Empagliflozin dosage and evidence

What is Empagliflozin?

How does Empagliflozin work?

It blocks a pump in the kidney called SGLT2. That pump normally pulls sugar back out of the urine. With it blocked, the sugar leaves the body. The heart and kidney benefit is bigger and faster than lower blood sugar alone explains. Nobody fully knows why. The leading ideas: less fluid in the blood, so the heart works less hard. Lower pressure inside the kidney's filters. The heart switching to a different fuel called ketones. And less salt build-up inside heart cells. The mouse work adds more ideas, like energy-sensing switches in cells and changes in gut bacteria. Those come from mice, which is a much weaker kind of evidence than the big human studies.

What have studies in people found about Empagliflozin?

Strong for heart, kidney and blood sugar disease. Zero for ageing. More than 23,000 people took part in the four big studies. None of them measured anything about ageing.

• 7,020 people with type 2 diabetes and heart disease: over about 3.1 years, 5.7 percent died on the drug and 8.3 percent on a dummy pill.
• 6,609 people with kidney disease: kidneys got worse or people died of heart disease in 13.1 percent on the drug and 16.9 percent on the dummy pill. But deaths from any cause, 4.5 percent against 5.1 percent, were too close to call.
• 5,988 people with heart failure whose hearts still pumped fairly well: 13.8 percent died of heart disease or went to hospital for heart failure, against 17.1 percent on the dummy pill. Most of that gap was fewer hospital stays, not fewer deaths.
• 3,730 people with heart failure and a weak pumping heart: the same result was 19.4 percent against 24.7 percent. It helped whether or not people had diabetes.
• No study in people has measured lifespan, biological age, frailty or any other sign of ageing on this drug.

What this does not tell you: Everyone in these studies had diabetes, heart failure or kidney disease. The drug helped by preventing heart deaths and hospital stays those people were at real risk of. A healthy 45 year old is not at much risk of those in the next three years. Nothing here tells you what the drug does to a healthy person over decades. And the known problems do not shrink in healthy people. Those are yeast infections of the genitals, losing too much fluid, and a dangerous acid build-up in the blood that can happen while blood sugar looks normal.

What do people who took Empagliflozin report?

This is what real people say happened to them, good and bad. Nobody measured it. A report cannot tell a real effect from the lift people get just from expecting it to work, from a diet or training change made at the same time, or from what was really in the vial. We still put it near the top. It is the next best thing to a study in people: what happens when real people use it, including what goes wrong.

• Yeast infections of the genitals are the most common complaint. The big studies found this too, so it is not just a rumour. Both men and women get them, women more often.
• Peeing more, feeling thirsty and feeling a little dried out are near universal early on. People already on water pills describe feeling dizzy when they stand up.
• Many people say they lost a few kilograms. That is expected, because you pee out sugar calories. It has nothing to do with ageing.
• The serious one is a dangerous acid build-up in the blood, called ketoacidosis. Online talk keeps playing it down, because blood sugar looks normal while it happens. Fasting, low carb eating, being sick and surgery all raise the risk. A finger-prick sugar meter will not warn you.

Sources: Longevity forums, diabetes communities and clinic write-ups. Uncontrolled self-report, useful for knowing what to watch for and worthless as evidence of an ageing effect.

The state of the research

The evidence, in charts

The studies we cite

• Study in people2015
  Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes

  A diabetes drug that turned out to keep people alive. 7,020 people with type 2 diabetes and high heart risk took empagliflozin or a dummy for about three years. 12.1 percent of the dummy group had a heart attack, had a stroke, or died of heart disease. On empagliflozin, 10.5 percent did. Deaths from any cause were 8.3 percent against 5.7 percent. Heart attacks and strokes alone did not change, so the gain came from fewer deaths. Genital infections were more common on the drug.

  EMPA-REG OUTCOME. 7,020 people with type 2 diabetes at high cardiovascular risk, median observation 3.1 years. The primary composite of cardiovascular death, nonfatal myocardial infarction or nonfatal stroke occurred in 10.5 percent on empagliflozin against 12.1 percent on placebo (hazard ratio 0.86, P = 0.04). Death from any cause was 5.7 percent against 8.3 percent, a 32 percent relative risk reduction. There was no significant difference in rates of myocardial infarction or stroke, and genital infection was more common on the drug.

  PMID 26378978 New England Journal of Medicine
• Study in people2020
  Cardiovascular and Renal Outcomes with Empagliflozin in Heart Failure

  It worked in heart failure as well, and it worked whether or not people had diabetes. 3,730 people with heart failure and a weakened pumping heart were followed for about 16 months. 24.7 percent of the dummy group died of heart disease or went into hospital for heart failure. On empagliflozin, 19.4 percent did. Kidney function declined about four times more slowly on the drug. These were people who already had heart failure, not healthy people taking it to prevent anything.

  EMPEROR-Reduced. 3,730 people with class II to IV heart failure and an ejection fraction of 40 percent or less, median 16 months. Cardiovascular death or heart failure hospitalisation occurred in 19.4 percent against 24.7 percent on placebo (hazard ratio 0.75). Estimated glomerular filtration rate fell by 0.55 against 2.28 ml per minute per 1.73 square metres per year. The effect held regardless of diabetes status.

  PMID 32865377 New England Journal of Medicine
• Study in people2021
  Empagliflozin in Heart Failure with a Preserved Ejection Fraction

  It helped the harder kind of heart failure, mostly by keeping people out of hospital. 5,988 people whose hearts still pumped reasonably well but who had heart failure symptoms were followed for a bit over two years. 17.1 percent of the dummy group died of heart disease or were admitted for heart failure. On empagliflozin, 13.8 percent were. The authors say the difference came mainly from fewer hospital admissions rather than from fewer deaths. That distinction matters to anyone reading this as a life-extending drug.

  EMPEROR-Preserved. 5,988 people with class II to IV heart failure and an ejection fraction above 40 percent, median 26.2 months. Cardiovascular death or heart failure hospitalisation occurred in 13.8 percent against 17.1 percent (hazard ratio 0.79). The authors state the effect was mainly driven by fewer heart failure hospitalisations rather than fewer deaths.

  PMID 34449189 New England Journal of Medicine
• Study in people2023
  Empagliflozin in Patients with Chronic Kidney Disease

  It slowed kidney disease down, and it did not stop people dying. 6,609 people with chronic kidney disease were followed for two years. Their kidney disease got worse, or they died of heart disease, in 16.9 percent of the dummy group against 13.1 percent on empagliflozin. Deaths from any cause were 5.1 percent against 4.5 percent, a gap too small to separate from chance. Anyone treating this drug as something that makes people live longer should stop at that last sentence.

  EMPA-KIDNEY. 6,609 people with chronic kidney disease, median 2.0 years. Kidney disease progression or cardiovascular death occurred in 13.1 percent against 16.9 percent (hazard ratio 0.72). Notably for anyone reading the drug as a mortality intervention, death from any cause was 4.5 percent against 5.1 percent and was not a significant difference in this trial.

  PMID 36331190 New England Journal of Medicine
• Animal study2024
  Empagliflozin rescues lifespan and liver senescence in naturally aged mice

  In mice. Naturally old male mice given empagliflozin lived 5.9 percent longer on average. They also did better on learning, memory and balance tests, weighed less, and showed fewer signs of worn-out cells in the liver. Their gut bacteria changed too. This is one lab's study, and nobody else has repeated it.

  The entire mouse lifespan case, from one laboratory. Empagliflozin extended the median survival of male mice by 5.9 percent, improved learning, memory and motor balance, lowered body weight, reduced hepatic P21 and P16, altered gut flora composition and raised short-chain fatty acids. A single-site study, not part of any multi-site replication programme.

  PMID 38922380 GeroScience
• Animal study2020
  Canagliflozin extends life span in genetically heterogeneous male but not female mice

  In mice. This is a different drug, canagliflozin, not empagliflozin. In the government mouse program, male mice given it in their food from 7 months old lived 14 percent longer on average. The longest-lived males lived 9 percent longer. It worked at all three test labs. Female mice got no benefit. Crediting this result to empagliflozin is a common mistake.

  This is the Interventions Testing Program SGLT2 result, and it is canagliflozin, not empagliflozin. Canagliflozin at 180 ppm in chow from 7 months of age extended median male survival by 14 percent and raised the 90th percentile survival age by 9 percent, with parallel effects at all three test sites. No lifespan benefit in females. Attributing this result to empagliflozin is a factual error that circulates widely.

  PMID 32990681 JCI Insight