A 52-week randomized controlled trial of ipragliflozin or sitagliptin in type 2 diabetes combined with metformin: The N-ISM study

Diabetes Obes Metab. 2021 Mar;23(3):811-821. doi: 10.1111/dom.14288. Epub 2021 Jan 8.

Abstract

Aim: 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).

Materials and methods: In a 52-week randomized open-label trial, we compared ipragliflozin and sitagliptin in Japanese patients diagnosed with type 2 diabetes, without prior ASCVD and treated with metformin. The primary endpoint was a glycated haemoglobin (HbA1c) reduction of ≥0.5% (5.5 mmol/mol) without weight gain at 52 weeks.

Results: Of a total of 111 patients (mean age 59.2 years, mean body mass index [BMI] 26.6 kg/m2 , 61.3% men), 54 patients received ipragliflozin and 57 received sitagliptin. After 52 weeks, achievement of the primary endpoint was not significantly different (37.0% and 40.3%; P = 0.72). HbA1c reduction rate at 24 weeks was greater for sitagliptin (56.1%) than for ipragliflozin (31.5%; P = 0.01). From 24 to 52 weeks, the HbA1c reduction with sitagliptin was attenuated, with no significant difference in HbA1c reduction after 52 weeks between sitagliptin (54.4%) and ipragliflozin (38.9%; P = 0.10). Improvements in BMI, C-peptide and high-density lipoprotein cholesterol were greater with ipragliflozin than with sitagliptin. Adverse events occurred in 17 patients with ipragliflozin and in 10 patients with sitagliptin (P = 0.11).

Conclusion: 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.

Keywords: DPP-4 inhibitor; SGLT2 inhibitor; clinical trial; glycaemic control; randomized trial; sitagliptin.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Diabetes Mellitus, Type 2* / complications
  • Diabetes Mellitus, Type 2* / drug therapy
  • Diabetes Mellitus, Type 2* / epidemiology
  • Dipeptidyl-Peptidase IV Inhibitors* / therapeutic use
  • Double-Blind Method
  • Drug Therapy, Combination
  • Female
  • Glucosides
  • Glycated Hemoglobin / analysis
  • Humans
  • Hypoglycemic Agents / therapeutic use
  • Male
  • Metformin* / therapeutic use
  • Middle Aged
  • Sitagliptin Phosphate / therapeutic use
  • Thiophenes
  • Treatment Outcome

Substances

  • Dipeptidyl-Peptidase IV Inhibitors
  • Glucosides
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Thiophenes
  • ipragliflozin
  • Metformin
  • Sitagliptin Phosphate