PMC8201990_01
Clinical course of the patient in this case. Hemoglobin A1c levels of the patient in this case show rapid reduction after oral administration of empagliflozin, with continuation of 15 mg/day pioglitazone and 1000 mg/day metformin, and 2.88 mg/day of subcutaneous metreleptin supplementation, with termination of insulin injection. The HbA1c level is maintained at ~8.0%, 18 months after empagliflozin initiation.
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Administration of 500 mg/day metformin and 15 mg/day pioglitazone, along with multiple daily subcutaneous injections of high-dose insulin (70 units/day) had failed to improve her hyperglycemia ( Figure 1 ). Her glycemic control improved, and the HbA1c value attenuated rapidly from 9.6% to 8.1% (National Glycohemoglobin Standardization Program: NGSP) (reference range, 4.6-6.2%); however, no further consistent improvement was observed, and her HbA1c levels increased to 11.3% before empagliflozin initiation ( Figure 1  and  Table 1 ). The area under the curve and fluctuations in the daily plasma glucose, measured using a flash glucose monitoring (FGM) system, demonstrated significant improvements ( Supplementary Figure 1 ). Furthermore, her triglyceride level had decreased to 652 mg/dL ( Table 2 ). For an additional 18 months from SGLT2 inhibitor initiation, her HbA1c level remained steady at 7.8% (NGSP); no specific adverse events, including urinary tract infection, were observed ( Figure 1  and  Table 1 ).
Evaluations of fat accumulation in the adipose and extra-adipose tissues. Body fat accumulation has been evaluated during the clinical course. (A) The time of evaluation using computed tomography (CT) imaging and magnetic resonance imaging as well as clinical time course of medications are presented. Fat accumulation in liver is decreased and eventually, not detected using the proton density fat fraction (PDFF) method and T1 subtraction imaging. Areas of visceral, subcutaneous, and total fat are increased, observed in the CT imaging analysis between before (B) and after (C, D) metreleptin and empagliflozin administrations, although muscle areas are not increased (E). Additionally, changes in fat volume and body mass index between before- and after-combination therapy using SGLT2 inhibitor and metreleptin administration are demonstrated. CT, computed tomography; PDFF, proton density fat fraction.
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Notably, body composition analysis using computed tomography imaging disclosed an increase in visceral and subcutaneous fat accumulation, with reduced liver steatosis and unchanged muscle areas ( Figure 2 ). Figure 2 ).