SGLT-2 Inhibitors and Adverse Effects

New Delhi: With the rising incidence of diabetes in the country, SGLT-2 inhibitors have emerged as one of the preferred modalities of treatment. However, like any other medicines, this class of medicines also comes with their own reported side effects.

Through a written reply, the Minister of State in the Ministry of Health and Family Welfare, Shri Ashwini Kumar Choubey, informed the members of the Lok Sabha about the adverse drug reactions associated with the use of these new class of anti-diabetes medicines (SGLT-2 inhibitors) in India. The minister provided a clear detailed breakup of side effects noted with these 4 types of SGLT-2 inhibitors associated in India, namely, Canagliflozin, Dapagliflozin, Empagliflozin, and Remogliflozin for the state of Karnataka.

Currently, CDSCO has given permission to import/market formulation of the following SGLT-2 inhibitors: Canagliflozin, Dapagliflozin & Empagliflozin including FDC like Canagliflozin + Metformin, Dapagliflozin + Metformin, Empagliflozin + Metformin & Empagliflozin + Linagliptin and manufacture/market of Remogliflozin and Remogliflozin + Metformin.

Responding to the question of whether the Government is aware of the fact that adverse drug reactions are associated with the use of a new class of anti-diabetes medicines (SGLT-2 inhibitors) in India, the minister informed that Central Drugs Standard Control Organisation (CDSCO) was notified about a Health Canada communication to all Sodium-Glucose Co-transporter-2 (SGLT2) inhibitor Marketing Authorization Holders regarding a Summary Safety Review (SSR) on the potential risk of pancreas inflammation (acute and chronic).

"United States Food & Drug Administration (USFDA) in its Drug Safety Communications (DSC) stated that cases of rare but serious infection of the genitals and area around the genitals have been reported with use of SGLT2 inhibitors. This serious rare infection, called necrotizing fasciitis of the perineum, is also referred to as Fournier's gangrene. USFDA has revised the labels of SGLT 2 inhibitors to include new warnings about the risk to patients. The issue has been examined in consultation with Subject Expert Committee (SEC) and information available under the pharmacovigilance programme of India has also been obtained," the minister informed.

Accordingly, CDSCO has requested all State Drug Controllers to direct the manufacturers of SGLT2 inhibitor class drugs such as Canagliflozin, Dapagliflozin, Empagliflozin, etc. under their jurisdiction to include the following warning in the package insert and promotional literature of these drugs:

Warning - Cases of a rare but serious infection of the genitals and area around the genitals have been reported with this class of type 2 diabetes medicines i.e., Sodium-Glucose Co-transporter-2 (SGLT2) inhibitors. This serious rare infection, called necrotizing fasciitis of the perineum, is also referred to as Fournier's gangrene.

Further, all the State Drug Controllers have been requested to direct the manufacturers of SGLT 2 inhibitor class drugs to include suitable warning in the package insert and promotional literature of these drugs, the minister informed.

Adverse Events Reported in the State of Karnataka

The minister provided the details of adverse effects in respect of SGLT-2 inhibitors reported under the Pharmacovigilance Programme of India (PvPI) from Karnataka as below: