Sodium-glucose Co Transporter 2 (sGLT2) Inhibitor and Endogenous Ketone Production

Completed · Phase 1

Conditions studied: Empaglifozin, Physiological Effects of Drugs, Hypoglycemic Agents, Sodium-Glucose Transporter 2 Inhibitors

In brief

Background: The drug empagliflozin treats diabetes. It lowers blood sugar by increasing glucose the kidneys excrete. This increases levels of ketones formed in the blood. The body makes ketones when it does not have enough glucose for fuel. The brains of many people with age-related diseases like Alzheimer's do not use glucose well. Brain use of ketones might improve mental ability. We investigated how empagliflozin affects ketone levels, which could lead to ways to improve brain health as people age. Objectives: To study how taking empagliflozin affects systemic and brain metabolism including ketone levels in people without diabetes. Eligibility: Adults at least 55 years old without diabetes Design: After a screening Visit, eligible participants were admitted to the NIA Clinical Unit during Visits 1 (baseline), 2 (first dose) and 3 (last/14th dose). On each Visit, blood draws were performed and circulating metabolites and hormones were repeatedly measured over 34-hour periods. Using plasma from fasting state only, we isolated total and neuronal-origin extracellular vesicles to measure proteins of the IGF-1 and insulin signaling cascades. Furthermore, on each Visit, we performed magnetic resonance spectroscopy (MRS) to measure concentrations of a plethora of metabolites in the brain. Between Visits 2 and 3, participants were taking the drug at home. A continuous glucose monitoring device was placed to detect potential glucose fluctuations while at home. The study was concluded for participants after the end of Visit 3.

Key facts

Study ID

NCT03852901

Run by

National Institute on Aging (NIA)

People needed

21

Starts

2019-03-28

Expected to finish

2021-12-13

Last updated by the study team

2022-08-02

Who can join

Age: 55 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Age 55 years and older.
• Healthy (see exclusion criteria below).
• Able to understand the study risks and procedures, and consent to participate in the study.
• Able to read and speak English.

You may not qualify if…

• History of diabetes (requiring any medical treatment other than diet and exercise) or fasting plasma glucose > 126 mg/dl or HbA1c> 6.5 %.
• History of hypoglycemia.
• BMI > 35 kg/m(2).
• Creatinine clearance less than 60 ml/min as measured by GFR.
• Glucosuria
• History of anemia within the past 6 months or Hgb <11.0 mg/dL for women and Hgb <12.5 mg/dL for men.
• Current steroid use or steroid use within 90 days of screening, excluding eye drops.
• Currently taking loop diuretics (Lasix, for example).
• Participant presently following a calorie restriction diet, low carb/high fat diet.
• HIV virus infection
• Hepatitis B infection, as evidenced by a positive HBsAG at screen visit.
• Hepatitis C infection that has not been treated. (The screen blood work must show HCV RNA quantitative is not detectable).
• Active infection/fever that may cause changes in glucose metabolism.
• Known allergy to sGLT2 inhibitors in the past.
• Thyroid dysfunction that is not controlled or treated. This will be determined by Free T3, T4, Free T4 or TSH not within MedStar Harbor Hospital laboratory normal ranges for this pilot study.
• Adrenal dysfunction as determined by a cortisol level not within the normal range for MedStar Harbor Hospital Laboratory for this pilot study.
• Kidney or liver disease, (GFR < 60 mL/min/1.73 m(2) and/or liver enzymes not within normal ranges for MedStar Harbor Hospital Laboratory for this pilot study.
• Severe gastrointestinal diseases such as Crohn s disease or ulcerative colitis requiring continuous treatment.
• History of severe pulmonary disease such as chronic obstructive pulmonary disease (COPD) or asthma requiring continuous medication use.
• Patients with known, or evidence of, peripheral vascular disease.
• History of chronic urinary tract infections.
• History of recurrent or recent dehydration in the past year.
• History of recurrent or recent vaginal yeast infection.
• Alcohol intake greater than 30 grams (drink more than 2 beers OR equivalent per day).
• History of severe psychiatric conditions associated with behavioral problems or requiring chronic medical treatment.

Where it is running

• National Institute on Aging, Clinical Research Unit — Baltimore, Maryland, United States

Full record on ClinicalTrials.gov

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