Metabolic effects of the dual SGLT 1/2 inhibitor sotagliflozin on blood pressure and body weight reduction in people with diabetes: An updated meta-analysis of randomized controlled trials.

AIM: To update the meta-analysis of the metabolic effects of a dual sodium-glucose co-transpoter-1/2 inhibitor, sotagliflozin, on blood pressure (BP) and body weight in people with diabetes. METHODS: An electronic search up to March 8, 2022, were conducted to determine eligible randomized-controlled trials of sotagliflozin-reporting BP and weight change outcomes in adults with diabetes. RESULTS: 16 trials were included, with a combined cohort of 19,140 patients. Compared with placebo, sotagliflozin had a mean systolic blood pressure reduction (weighted mean differences (WMDs) -2.60 mmHg, 95 % CI: -2.90 to -2.30), mean diastolic blood pressure reduction (WMD -0.96 mmHg, 95 % CI: -1.17 to -0.75), and mean weight loss (WMD -1.88 kg, 95 % CI: -2.16 to -1.59). Metabolic effects on BP-lowering and weight loss were observed across diabetes status, duration of follow-up, and chronic kidney disease comorbidity. Meanwhile sotagliflozin presented significant effects on people with type 1 diabetes and showed a dose-response relationship for BP-lowering and weight loss. CONCLUSION: This meta-analysis enriches the evidence on the metabolic benefits, including BP-lowering and weight loss, of sotagliflozin, and provide a reasonable therapeutic option for managing diabetes with metabolic syndrome. Further studies will be required to elucidate its long-term effects and role in metabolic syndrome management. PROSPERO REGISTRATION NUMBER: CRD42022323945.

Effects of SGLT2 Inhibitors beyond Glycemic Control-Focus on Myocardial SGLT1.

Selective sodium-glucose cotransporter 2 (SGLT2) inhibitors reduced the risk of hospitalization for heart failure in patients with or without type 2 diabetes (T2DM) in large-scale clinical trials. The exact mechanism of action is currently unclear. The dual SGLT1/2 inhibitor sotagliflozin not only reduced hospitalization for HF in patients with T2DM, but also lowered the risk of myocardial infarction and stroke, suggesting a possible additional benefit related to SGLT1 inhibition. In fact, several preclinical studies suggest that SGLT1 plays an important role in cardiac pathophysiological processes. In this review, our aim is to establish the clinical significance of myocardial SGLT1 inhibition through reviewing basic research studies in the context of SGLT2 inhibitor trials.

Pharmacokinetics, metabolism, and excretion of licogliflozin, a dual inhibitor of SGLT1/2, in rats, dogs, and humans.

Absorption, metabolism, and excretion (AME) of licogliflozin, a sodium-glucose co-transporters (SGLTs) 1 and 2 inhibitor, were studied in male rats, dogs, and healthy male volunteers and reported.Oral absorption of licogliflozin was rapid (tmax < 1 h) with absorption estimated at 87%, 100% and 77% in rats, dogs and humans, respectively.Excretion of licogliflozin-related radioactivity was rapid and nearly complete following oral administration with total radioactivity recovery ranging from 73% in dogs, 92.5% in humans, to 100% in rats. Dose-related radioactivity was excreted in both urine and faeces with urinary excretion playing a slightly more important role in humans (∼56%) than in animal species (∼19-41%).Elimination of licogliflozin was predominantly via metabolism with the majority of the radioactivity dose (∼54-74%) excreted as metabolites across species.The principal biotransformation pathways involved direct glucuronidation and oxidation across all species. In humans, direct glucuronidation to M17 and M27 was the major pathway observed, accounting for ∼38% of the dose in excreta while oxidative metabolism also contributed to >29% of the dose in excreta. Oxidative pathways were predominant in animal species.