Role of SGLT2 Inhibitors in Diabetes Management: Focus on HbA1c Levels, Weight Loss and Genetic Variation

Abstract

Sodium Glucose Co-transporters-2 (SGLT2) inhibitors are the recent addition to treatment strategies for Type 2 Diabetes Mellitus (T2DM). It is a non-insulin dependent anti-diabetic therapeutic approach that eliminates plasma glucose by urination. The study was carried out with the aim of evaluating the effect of SGLT2 inhibitors on HbA1c levels and weight loss in responders and non-responders. In addition, the role of two significant variants, SLC5A2 (rs9934336) and UGT1A9 (rs72551330), affecting the inter-individual variation in response to SGLT2 inhibitors was evaluated in the study population. 200 confirmed T2DM patients on SGLT2 inhibitors were enrolled for the study. Patients with decreased HbA1c levels and body weight were categorized as responders, whereas the ones who did not show a significant decrease in these two parameters after treatment were categorised as non-responders. Association of HbA1c levels and weight loss before as well as after treatment with responders and non-responders was evaluated. Patients were screened for two significant variants, SLC5A2 (rs9934336) and UGT1A9 (rs72551330), affecting the inter-individual variation in response to SGLT2 inhibitors by Sanger Sequencing. A significant difference in HbA1c levels and weight was found in responders and non-responders before and after the treatment. However, both of the variants, SLC5A2 (rs9934336) and UGT1A9 (rs72551330), were not found to be significantly associated with the drug response. In conclusion, SGLT2 inhibitors reduced HbA1c levels and weight effectively in responders. However, the targeted gene variants need not to be involved in genetic testing before prescribing this class of drugs to T2DM patients from Malwa region of Punjab. Highlights:

1. Treatment of Type 2 diabetes mellitus (T2DM) with Sodium Glucose co-transporter-2 (SGLT2) inhibitors is an insulin-independent method of reducing blood glucose levels by lowering renal tubular glucose reabsorption.
2. Significant decrease in HbA1c levels and weight loss in responders was observed after the treatment with SGLT2 inhibitors.
3. Pharmacogenetic analysis was carried out for two gene variants, SLC5A2 (rs9934336) and UGT1A9 (rs72551330), reported to be involved in inter-individual response to SGLT2 inhibitors.
4. None of the tested variants were found to be significantly associated with inter-individual response to SGLT2 inhibitors.
5. Pharmacogenetic testing for the two most commonly reported variants is not required for the T2DM patients on SGLT2 inhibitors from the Malwa region of Punjab.