Ipragliflozin Vs Sitagliptin in T2D with Metformin: A glimpse of NISM study

Dipeptidyl peptidase‐4 (DPP‐4) inhibitors are widely used in the treatment of diabetes because they do not cause weight gain and are associated with a low risk of hypoglycaemia. SGLT2 inhibitors are also widely used because of their weight‐loss effects and evidence of prevention of ASCVD, chronic kidney disease, and heart failure. However, the results of studies comparing the efficacy of these drugs as second‐line drugs after metformin in patients at low‐risk of ASCVD are controversial. Previous study findings indicate that a 24‐week period is not sufficient, to evaluate the efficacy of either drug and suggests for a long‐term randomized controlled trial to produce meaningful results. Therefore, researchers of Japan conducted NISM study to compare the long‐term efficacy of sodium‐glucose co‐transporter‐2 inhibitors and dipeptidyl peptidase‐4 inhibitors as second‐line drugs after metformin for patients, not at high risk of atherosclerotic cardiovascular disease (ASCVD).

It was a 52‐week, long‐term, prospective, randomized, open‐label, controlled trial in Japanese patients with type 2 diabetes, who had an inadequate response to metformin and no history of ASCVD. Researchers included a total of 111 patients and randomly assigned them to receive either ipragliflozin (n=54) or sitagliptin (n=57). The primary endpoint assessed were glycated haemoglobin (HbA1c) reduction of ≥0.5% (5.5 mmol/mol) without weight gain at 52 weeks.

Key findings of the study were:

• By the end of 52 weeks, researchers noted no significant difference between the group in reducing the HbA1c level (37.0% and 40.3%); however, at 24 weeks, they noted that the significant HbA1c reduction rate was greater in patients who received sitagliptin (56.1%) than in patients who were on ipragliflozin (31.5%).

• They also noted the effect of sitagliptin from week 24 to 52 attenuated, with no significant difference in HbA1c reduction after 52 weeks between sitagliptin (54.4%) and ipragliflozin (38.9%).

• They found improvements in BMI, C‐peptide and high‐density lipoprotein cholesterol were greater with ipragliflozin than with sitagliptin.

• They reported 17 adverse events with ipragliflozin and 10 with sitagliptin.

The authors concluded, "The HbA1c‐lowering effect at 24 weeks was greater with sitagliptin than with ipragliflozin, but with no difference in efficacy related to HbA1c and body weight at 52 weeks. However, some ASCVD risk factors improved with ipragliflozin".

For further information:

https://dom-pubs.onlinelibrary.wiley.com/doi/10.1111/dom.14288