CHEARS

2-Deoxy-D-glucose is a drug that has been recently approved for the treatment of Covid -19 as an add-on/ adjuvant therapy in moderate to severe cases by DCGI. In glucose, there is hydrogen group and hydroxyl group such that, on second carbon, this oxygen is deleted and replaced by hydrogen group thus called as 2 Deoxy-D-glucose or the 2-Deoxy-Dextro glucose.

Development of 2-DG

DRDO initiated the development of an anti-COVID therapeutic application of 2-DG. In April 2020, during the first wave of the pandemic, INMAS-DRDO scientists conducted laboratory experiments with the help of the Centre for Cellular and Molecular Biology (CCMB), Hyderabad, to check the efficacy of this molecule against the SARS-CoV-2 virus and the property of inhibiting the viral growth and its replication.

After obtaining a positive result, approval for phase II trials was given by DCGI and CDSCO in May 2020 till October. The Trial was conducted in partnership with industry DRL, Hyderabad. The trial was conducted in 2 subdivided phases -Phase IIa and Phase IIb.

Phase IIa was conducted in 6 hospitals and Phase IIb was conducted in 11 hospitals in a total of 110 patients. Trends showed that patients treated with 2 -DG showed faster symptomatic relief than the standard of cure on various endpoints.

After the Phase II result, the Phase III trial was approved in November 2020 on 220 patients at 27 hospitals in different states of the country.

Efficacy of 2-DG in clinical trails

In the 2-DG arm, a significantly higher proportion of patients improved symptomatically and became free from the requirement of supplemental oxygen (42% v/s 31%) within day 3, in comparison to SoC, Indicating an early relief from Oxygen Therapy/ oxygen dependence. From day 3 to day 8, RT-PCR was found to be negative rather than a normal 15 days to 1-month schedule. A similar trend of recovery was also observed in patients aged more than 65 years as well.

More about 2-DG:

It has been used in cancer, preventing the entry of glucose towards cancerous cells and preventing its growth. By inhibiting these glucoses supply,it prevents the cancerous cells from further growing.

In covid 19, it accumulates in the virally infected cells and thereby inhibits the viral synthesis and its energy production (ace-2 receptor gets attached with coronavirus whereas, on the administration of this drug, it inhibits this binding of the ace-2 receptor with coronavirus thereby inhibiting its growth.

2-DG is a generic molecule therefore it’s easy for producing in bulk

How to administer 2-DG?

It’s in powder form with every sachet containing 2.34 grams of 2-DG

It is dissolved in water as like normal glucose powder and then consumed

In Covid 19 patients it is taken twice daily for 5-7 days

It’s not advisable for the outpatient department and strictly under the surveillance of healthcare professionals

Will 2-DG work on every variant?

Yes, it’s found to be effective against all variants of the coronavirus(director of INMA explained on all India radio)

Availability and Price:

The price is not fixed yet. Initially, they are 10,000 sachets available, but they are currently under use only in AIIMS, armed forces, and DRDO attached hospitals, It will start to get circulated to all hospitals by the month of June.

Other Indications of 2-DG

1)Refractory epilepsy Treatment:

Refractory epilepsy needs to get treated with the keto diet and it was found that 2-DG can substitute or mimic the ketogenic diet, and it’s also a great promise as a new anti-epileptic drug (Garriga -Canut et.al). It increases the expression of brain-derived neurotrophic factor (BDNF), Nerve growth factor(NGF), Arc protein(ARC), and Basic fibroblast growth factor (FGF2).

2) Anti-cancer treatment: Recommended dosage is 63mg/kg/day but this drug is associated with several adverse effects on its excessive usage.

Prolongation of the Q-T interval: it was found that the majority of patients (66%) ended up with torsade-de- points causing polymorphic ventricular tachycardia on excessive usage.

Hyperglycemia:2-DG can increase the blood glucose level therefore it's recommended to increase insulin dosage or monitor blood glucose levels.

3)FDG-PET scan

2DG has been used as a targeted optical imaging agent for fluorescent in vivo imaging.In clinical medical imaging (PET scanning, fluorodeoxyglucose is used, where one of the 2-hydrogens of 2-deoxy-d-glucose is replaced with the positron-emitting isotope fluorine-18 which emits paired gamma rays allowing distribution of the tracer to be imaged by external gamma camera(s)

Mechanism of action

Glycolysis is an aerobic pathway, such that In glycolysis energy is utilized and later it’s released (Glucose gets converted into pyruvate with ATP production) however in the case of 2-DG when 2-DG enters the virus, it gets converted into 2-d-glucose -6-phosphate (on the presence of the enzyme hexokinase). This molecule would inhibit the hexokinase enzyme causing inhibition of the further glycolysis of 2-DG. Therefore, Pyruvate conversion is inhibited, preventing its energy production. Henceforth, on consuming 2-DG, it gets accumulated on virus-specific cells thus inhibiting its proliferation and killing these virus particles. Furthermore, for glycolysis to occur there is a need for oxygen such that on glycolysis inhibition oxygen consumption is also reduced, which could be later on utilized for the energy production from other sources such as fat, proteins thus reducing the oxygen requirement for the body (2-DG decreases the oxygen requirement by almost 43%).

Conclusion

• A brand-new drug used as a treatment for covid 19

• Given to moderate to severe covid-19 patients.

• Currently used only in AIIMS, armed forces, and DRDO attached hospitals, but the data regarding the usage of about 10000 doses from these hospitals are still pending.

• Its dosage recommended is 2 sachets per day for 5-7 days either before or after food. It's available in powder forms like glucose which is dissolved in water and consumed

• Cot of this drug has not been fixed yet.

• There are adverse effects like Q-T prolongation and hyperglycemia

• This drug is not a substitute but an add-on to covid treatments

• There is no interaction between Insulin or OHA with 2-DG

• Monitor blood glucose in DM patients

• 2-DG is viral cells specific therefore it won’t affect any other normal cells.

• Don’t use in uncontrolled diabetes mellitus and patients with torsade de points

• Significant favorable trend 2.5 days difference was noted in terms of median time to achieving normalization specific vital signs parameters when compared to SoC