The Long-term Effect of mTOR inhibition on Lipid and Glucose Metabolism

Here is an excellent paper on MTOR inhibition on lipids and glucose over the long term in patients being treated with everolimus (and some sirolimus). MTORi dosages usually started at 5 or 10 mg daily (for everolimus). What is the conversion factor for Everolimus to Rapamycin?

mTOR inhibitors are known to induce dyslipidemia in 25–76% and hyperglycemia in 13–50% of patients [810].

In the EXIST trials (follow-up up to 5 years), the phase III trials that led to approval of mTOR inhibition in TSC patients, dyslipidemia was reported in 5–30%, but no new cases of diabetes were reported [3, 4, 6]. In a small prospective study among mainly children with TSC using mTOR inhibition, dyslipidemia and hyperglycemia were reported in 72% and 22% of children, respectively, but the highest fasting glucose did not reach diabetic levels (108 mg/dl (6 mmol/l)) [11].

We included 141 patients, the median age was 36 years, median use of mTOR inhibitors 5.1 years (aimed serum levels 3.0–5.0 µg/l). Total cholesterol, LDL- and HDL-cholesterol levels at baseline were similar to healthy reference data. After start of mTOR inhibition therapy, total cholesterol, LDL-cholesterol and triglycerides increased significantly and were higher compared to healthy reference population. Mean total cholesterol levels increased by 1.0 mmol/L after 3–6 months of mTOR inhibition therapy but did not increase further during follow-up. In this study, 2.5% (3/118) of patients developed diabetes (defined as an HbA1c ≥ 48 mmol/mol) during a median follow-up of 5 years.

I didn’t know that Rapamycin was an effective treatment for the following diseases:

MTOR inhibitors (mTORi) are very effective in treating rAML (> 30% size reduction after 4–5 years in more than 80% of patients), SEGA (response rate 100%) and epilepsy (response rate 40%) [26].


@DeStrider Great find. Thanks.

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