Ipragliflozin L-Proline

Assess the efficacy and safety profiles of different sodium-glucose cotransporter-2 inhibitors (SGLT2is) as an add-on to metformin in type 2 diabetes mellitus (T2DM) patients.

Bayesian network meta-analysis.

PubMed, Embase, Cochrane Library, Web of Science and ClinicalTrials.gov were searched before 18 December 2024.

Randomised controlled trials (RCTs) evaluating T2DM patients taking one of 12 SGLT2is as add-on therapy to metformin. Efficacy outcomes focused on glycated haemoglobin (HbA1c) reduction, fasting plasma glucose (FPG) reduction and weight loss (WL). Safety outcomes included adverse events (AEs), serious AEs (SAEs), hypoglycaemia, urinary tract infections (UTI) and genital infections (GI).

Two investigators independently extracted data. The quality of the included studies was assessed using the Cochrane Risk of Bias Tool (V.2.0) for RCTs.

23 RCTs involving 9144 patients and 11 SGLT2is were included. Compared with placebo, most SGLT2is reduced HbA1c (mean difference (MD), −0.45~−0.80%), FPG (MD, −0.78~−2.02 mmol/L) and body weight (MD, −0.88~−2.67 kg). Only 10 mg of henagliflozin increased the incidence of AEs, and none of the included interventions increased the risks of SAEs or UTIs. 50 mg of empagliflozin exhibited higher risks of hypoglycaemia. Only 10 mg of empagliflozin increased the risk of GI. According to the surface under the cumulative ranking values, SGLT2is with optimal efficacy and safety were 15 mg of ertugliflozin in HbA1c reduction, 300 mg of canagliflozin in FPG reduction, WL and hypoglycaemia, 400 mg of sotagliflozin in total AEs, 10 mg of ertugliflozin and 150 mg of ipragliflozin in SAEs, 12.5 mg of ipragliflozin in UTI and 1 mg of ertugliflozin in GI.

As add-on therapy, SGLT2is demonstrated favourable antidiabetic efficacy and acceptable safety. 300 mg of canagliflozin was the best option among the included interventions considering favourable glucose control and WL. Some novel SGLT2is (eg, henagliflozin) exhibited promising efficacy and safety profiles, but more research is needed to validate the findings.

A 58-year-old woman with a body mass index of 26.4 kg/m² was referred because of high glycated hemoglobin (HbA1c) at a medical checkup. Her anti-glutamic acid decarboxylase antibody (GADA) titer was positive (16.0 U/mL; normal < 5.0 U/mL). Her HbA1c was controlled at 6.4%-7.5% using metformin, ipragliflozin, and sitagliptin. Two-and-a-half years later, she was diagnosed with endometrial cancer with pelvic lymph node metastasis and underwent surgery followed by chemotherapy with carboplatin and paclitaxel, then carboplatin and docetaxel. However, owing to enlargement of the metastatic nodules, combination therapy with pembrolizumab and lenvatinib (pem + len) was initiated (DAY 1). On DAY 36, her plasma glucose (PG) concentration was high; therefore, insulin degludec was administered once daily and self-monitoring of blood glucose commenced. On DAY 50, her PG and HbA1c were 509 mg/dL and 10.2%, respectively, and her insulin therapy was changed to a basal-bolus. Urinary ketones were negative. Treatment with pem + len was continued without interruption. Her GADA was negative 3 months before starting pem + len (DAY - 119), but was high (234 U/mL) on DAY 50, and then negative on DAYs 345 and 670. Her serum C-peptide concentration gradually decreased, but it did not disappear (DAYs - 119, 50, 156, 345, 607 and 670: 2.49, 1.80, 0.90, 0.21, 0.85 and 0.65 ng/mL, respectively). Human leukocyte antigen analysis revealed two susceptibility haplotypes (DRB1^*04:05-DQB1^*04:01-DPB1^*02:01 and DRB1^*04:05-DQB1^*04:01-DPB1^*05:01) for type 1 diabetes (T1D). This case is notable in that pembrolizumab-related T1D progressed more slowly than previously reported, and lenvatinib may have contributed to this delay.