Dataset Information

Efficacy and safety of ipragliflozin in Japanese patients with type 2 diabetes and inadequate glycaemic control on sitagliptin.

ABSTRACT:

Aims

To assess the efficacy, safety and tolerability of ipragliflozin 50 mg once daily added to sitagliptin 50 mg once daily monotherapy in Japanese patients with type 2 diabetes (T2D).

Materials and methods

The results of two clinical trials are reported. In both trials, patients had glycated haemoglobin (HbA1c) levels of 7.0% to 10.0% on sitagliptin 50 mg once daily 2 weeks prior to addition of ipragliflozin or placebo. In one trial (Trial 843), patients were randomized 1:1 to addition of blinded ipragliflozin 50 mg once daily (n = 73) or placebo (n = 70) for 24 weeks; the primary endpoint was efficacy (change in HbA1c at Week 24). In the other trial (Trial 849), open-label ipragliflozin 50 mg once daily was added for 52 weeks (n = 77); the primary objective was to assess safety/tolerability.

Results

In Trial 843, baseline characteristics were similar between groups (mean age 60.5 years, HbA1c 8.0%); after 24 weeks, adding ipragliflozin provided significantly greater reduction in HbA1c compared to placebo: least squares mean difference -0.77% (95% confidence interval -0.98, -0.57; P <0.001). In Trial 843, the incidences of adverse events (AEs) overall and prespecified AEs of clinical interest (symptomatic hypoglycaemia, urinary tract infection, genital infection, hypovolaemia, and polyuria/pollakiuria) were similar between groups. In Trial 849, specific AEs with incidence ≥5% were nasopharyngitis, pollakiuria, back pain, thirst, constipation, influenza and arthralgia; drug-related AEs reported in ≥2 patients were pollakiuria, thirst and constipation.

Conclusions

Ipragliflozin 50 mg once daily added on to sitagliptin 50 mg once daily monotherapy provided significant improvement in glycaemic control and was generally well tolerated in Japanese patients with T2D. ClinicalTrials.gov: NCT02577003, NCT02564211.

SUBMITTER: Kaku K

PROVIDER: S-EPMC8453748 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:AIMS:To assess the safety and efficacy of monotherapy with once-weekly subcutaneous (s.c.) semaglutide vs sitagliptin in Japanese people with type 2 diabetes (T2D). METHODS:In this phase IIIa randomized, open-label, parallel-group, active-controlled, multicentre trial, Japanese adults with T2D treated with diet and exercise only or oral antidiabetic drug monotherapy (washed out during the run-in period) received once-weekly s.c. semaglutide (0.5 or 1.0?mg) or once-daily oral sitagliptin 100?mg. The primary endpoint was number of treatment-emergent adverse events (TEAEs) after 30?weeks. RESULTS:Overall, 308 participants were randomized and exposed to treatment, with similar baseline characteristics across the groups. In total, 2.9% of participants in both the semaglutide 0.5?mg and the sitagliptin group prematurely discontinued treatment, compared with 14.7% in the semaglutide 1.0?mg group. The majority of discontinuations in the semaglutide 0.5 and 1.0?mg groups were attributable to adverse events (AEs). More TEAEs were reported in semaglutide- vs sitagliptin-treated participants (74.8%, 71.6% and 66.0% in the semaglutide 0.5?mg, semaglutide 1.0?mg and sitagliptin groups, respectively). AEs were mainly mild to moderate. Gastrointestinal AEs, most frequently reported with semaglutide, diminished in frequency over time. The mean glycated haemoglobin (HbA1c [baseline 8.1%]) decreased by 1.9% and 2.2% with semaglutide 0.5 and 1.0?mg, respectively, vs 0.7% with sitagliptin (estimated treatment difference [ETD] vs sitagliptin -1.13%, 95% confidence interval [CI] -1.32; -0.94, and -1.44%, 95% CI -1.63; -1.24; both P?<?.0001). Body weight (baseline 69.3?kg) was reduced by 2.2 and 3.9?kg with semaglutide 0.5 and 1.0?mg, respectively (ETD -2.22?kg, 95% CI -3.02; -1.42 and -3.88?kg, 95% CI -4.70; -3.07; both P?<?.0001). CONCLUSIONS:In Japanese people with T2D, more TEAEs were reported with semaglutide than with sitagliptin; however, the semaglutide safety profile was similar to that of other glucagon-like peptide-1 receptor agonists. Semaglutide significantly reduced HbA1c and body weight compared with sitagliptin.

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