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The Prediabetes Nutritionist

Jardiance Reduces Brain Insulin Resistance, Fasting Blood Glucose in Prediabetes

Jardiance (empagliflozin), a sodium-glucose cotransporter 2 (SGLT2) inhibitor, increases brain insulin sensitivity and reduces fasting blood glucose and liver fat in individuals with prediabetes, a new randomised clinical study reports. 

Jardiance also reduces body fat despite participants maintaining their regular diets.

The study, “Empagliflozin improves insulin sensitivity of the hypothalamus in humans with prediabetes: a randomised, double-blind, placebo-controlled, phase 2 trial,” was published in Diabetes Care

Insulin action in the brain regulates eating behaviour, body weight and body fat levels. Some individuals have reduced or absent responses to insulin, a condition termed brain insulin resistance. 

Animal studies have shown that brain insulin resistance promotes obesity and whole-body insulin resistance, increasing diabetes risk. In support of this, recent human studies have linked brain insulin resistance to long-term weight gain and unhealthy body fat distribution.

SGLT2 inhibitors are therapeutic drugs that lower blood sugar by reducing the amount of glucose the kidneys absorb, with the remaining glucose excreted through urine. When given to obese, insulin-resistant mice, SGLT2 inhibitors restores brain insulin sensitivity, improving whole-body insulin resistance and lowering inflammation. However, whether these inhibitors can reduce brain insulin resistance in humans is unknown. 

To bridge this knowledge gap, a team of scientists in Germany investigated the effects of jardiance, on brain insulin resistance in overweight and obese patients with prediabetes. 

The study was conducted at the University Hospital of Tübingen between July 2017 and October 2019. Participants were given either 25 mg jardiance or a placebo once daily for eight weeks. Before and after treatment, the researchers assessed participants brain insulin sensitivity via MRIs after taking nasal insulin and liver fat levels. Participants also completed food dairies to determine their usual food intake and questionnaires to evaluate their hunger levels.

A total of 40 individuals (65% female) with a mean age of 60 years and body mass index (BMI) of 31.5 completed the study. Of the cohort, 19 received jardiance and 21 the placebo. Baseline characteristics, including fasting blood glucose, glycated haemoglobin (HbA1c) and insulin resistance were similar in both groups. 

After eight weeks of treatment, brain insulin response significantly improved in the jardiance group, while no change occurred in the placebo group. Participants in the jardiance group also experienced significantly reduced hunger and fasting blood glucose levels. However, HbA1c and two-hour glucose after the oral glucose tolerance test remained the same in both groups. 

Interestingly, while body weight and BMI remained the same in both groups, only participants in the empagliflozin group reduced their body fat levels. 

“Whole-brain analysis detected significant changes in insulin action in the brain in response to empagliflozin [jardiance] in one specific brain area: the hypothalamus… More importantly, the brain response to insulin after empagliflozin treatment was independent of body weight, which by itself is closely linked to insulin sensitivity of at least some brain areas,” the researchers wrote. 

Many patients in the study had fatty liver disease and remarkably, participants treated with empagliflozin displayed significantly reduced liver fat, while those treated with placebo displayed increased liver fat. 

“…we confirm a clinically relevant reduction of liver fat content upon empagliflozin treatment. Of note, this response was most likely not due to weight loss but was mediated via improved hypothalamic insulin action. Our results suggest that the reversal of hypothalamic insulin resistance by empagliflozin might restore brain-derived regulation of liver metabolism with a subsequent reduction of liver fat content,” they wrote. 

The researchers highlighted the uneven distribution of sexes in the treatment groups as a study limitation. 

“In summary, we detected restored hypothalamic insulin sensitivity upon treatment with empagliflozin in people with prediabetes…this effect could contribute to the observed reduction in liver fat content and fasting blood glucose, which are major risk factors for diabetes and cardiovascular complications,” the researchers wrote.

Further research is needed to determine how empagliflozin affects other organs in the body besides the brain. 

Still, “our current findings reveal that brain insulin resistance is a condition that is treatable by pharmacological intervention with potential benefits for adiposity [body fat levels] and whole-body metabolism,” they concluded.

The Key Takeaway

Some people with prediabetes have brain insulin resistance, which promotes obesity and insulin resistance in the rest of the body. Jardiance increase brain insulin sensitivity in these patients, which reduces body fat, fasting blood glucose, and liver fat. Remarkably, this happens without weight loss. 

Jardiance is currently only used to treat people with type 2 diabetes. This study only included 40 participants; therefore, more research is needed before they are recommended for people with prediabetes. However, these findings are encouraging, especially for those who need medication to supplement lifestyle changes. 

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