BACKGROUND: To systematically evaluate the efficacy and safety of sotagliflozin (SOTA) adjuvant therapy for type 1 diabetes mellitus (T1DM).
METHODS: Through April 2019, the Web of Science, PubMed, Cochrane Library, Embase, and China National Knowledge Infrastructure databases were electronically searched to identify randomized controlled trials exploring SOTA adjuvant therapy for T1DM. Strict screening and quality evaluations of the obtained literature were performed independently by 2 researchers. Outcome indexes were extracted, and a meta-analysis of the data was performed using Revman 5.3 software.
RESULTS: A total of 7 randomized controlled trials were included. The meta-analysis results showed that compared with the patients in the placebo group, the patients in the SOTA group had a lower hemoglobin A1c (mean difference [MD] = -0.28, 95% confidence interval [CI] [-0.34, -0.22], P < .01), lower total daily insulin use (MD = -8.89, 95% CI [-11.64, -6.13], P < .01), faster weight loss (MD = -3.03, 95% CI [-3.79, -2.26], P < .01), better fasting blood glucose and 2-hour postprandial blood glucose control (MD = -0.75, 95% CI [-1.04, -0.45], P < .01; MD = -2.42, 95% CI [-3.17, -1.67], P < .01), and a higher rate of well-controlled glucose levels (relative risk = 1.75, 95% CI [1.55, 1.99], P < .01), while no significant difference in the incidence of severe hypoglycemic events was found between the SOTA and placebo groups (risk difference [RD] = -0.01, 95% CI [-0.02, 0.00], P = .13). The incidence of diabetic ketoacidosis was higher in the SOTA group than in the placebo group (RD = 0.03, 95% CI [0.02, 0.04], P < .01). The incidence of genital mycotic infection was higher in the SOTA group than in the placebo group (RD = 0.06, 95% CI [0.05, 0.08], P < .01). No significant difference in the incidence of urinary tract infections was detected between the SOTA group and the placebo group (RD = 0.00, 95% CI [-0.01, 0.01], P = 0.97).
CONCLUSIONS: SOTA is a potential drug for the treatment of T1DM and is effective for controlling blood sugar. The main adverse reactions to SOTA are genital mycotic infections and diabetic ketoacidosis. We must further assess the severity of diabetic ketoacidosis caused by SOTA.

Sotagliflozin (Zynquista™) is the first dual inhibitor of sodium-glucose co-transporter-1 and -2 (SGLT1 and 2). In the phase 3, inTANDEM 1-3 trials, adjunctive use of oral sotagliflozin (200 mg or 400 mg once daily) improved glycaemic control and reduced bodyweight and insulin requirements relative to placebo over 24 weeks of treatment in adults whose type 1 diabetes (T1D) was inadequately controlled by insulin therapy. Similar benefits were seen with the drug in patients who were overweight/obese [i.e. body mass index (BMI) ≥ 27 kg/m2] in inTANDEM 1 and 2 (pooled). The benefits of sotagliflozin were largely maintained over 52 weeks of treatment. Overall, use of sotagliflozin in this setting is generally well tolerated and reduces, or at least does not increase, the likelihood of hypoglycaemia; however, as with other SGLT inhibitors, sotagliflozin carries a risk of diabetic ketoacidosis (DKA). On the basis of its risk/benefit profile, sotagliflozin is indicated in the EU as an adjunct to insulin in adults with T1D with a BMI ≥ 27 kg/m2 who have failed to achieve adequate glycaemic control despite optimal insulin therapy, thus expanding the currently limited adjunctive oral treatment options available for use in this population.

Glucose transport across the intestinal brush border membrane plays a key role in metabolic regulation. Depending on the luminal glucose concentration, glucose is mainly transported by the sodium- dependent glucose transporter (SGLT1) and the facilitated-transporter glucose transporter (GLUT2). SGLT1 is apical membrane-constitutive and it is active at a low luminal glucose concentration, while at concentrations higher than 50 mM, glucose is mainly transported by GLUT2 (recruited from the basolateral membrane). Dietary phenolic compounds can modulate glucose homeostasis by decreasing the postprandial glucose response through the inhibition of SGLT1 and GLUT2.
Phenolic inhibition of intestinal glucose transport has been examined using brush border membrane vesicles from rats, pigs or rabbits, Xenopus oocytes and more recently Caco-2 cells, which are the most promising for harmonizing in vitro experiments.
Phenolic concentrations above 100 µM has been proved to successfully inhibit the glucose transport. Generally, the aglycones quercetin, myricetin, fisetin or apigenin have been reported to strongly inhibit GLUT2, while quercetin-3-O-glycoside has been demonstrated to be more effective in SGLT1. Additionally, epigallocatechin as well as epicatechin and epigallocatechin gallates were observed to be inhibited on both SGLT1 and GLUT2.
Although, valuable information regarding the phenolic glucose transport inhibition is known, however, there are some disagreements about which flavonoid glycosides and aglycones exert significant inhibition, and also the inhibition of phenolic acids remains unclear. This review aims to collect, compare and discuss the available information and controversies about the phenolic inhibition of glucose transporters. A detailed discussion on the physicochemical mechanisms involved in phenolics-glucose transporters interactions is also included.

Patients with type 1 diabetes mellitus (T1DM) are insulin dependent. Infection increases insulin resistance and subsequently increases insulin needs. We are reporting a case of a patient with T1DM and severe infection who has reduced insulin needs after starting micafungin therapy.
A 29-year-old Hispanic woman with known history of long-standing, uncontrolled T1DM presented for evaluation of worsening dysphagia and dyspnea. She was found to have cervical necrotizing fasciitis extending into the mediastinum and required several debridement surgeries along with broad-spectrum antibiotics and antifungal therapy. She had uncontrolled diabetes with a glycosylated hemoglobin of 13.4% (18.8 mM) on admission. Her insulin requirements progressively increased as a result of worsening infection, continuous tube feeds, and multiple debridement surgeries. She was started on micafungin, a potent 1,3-β-D glucan synthase inhibitor, to broaden antimicrobial coverage when her insulin requirement decreased to zero for >48 hours. Right after discontinuation of micafungin and her switch to a different antifungal, insulin requirements increased back to her baseline needs.
This is a report of decreased insulin requirements in a patient with T1DM correlating with micafungin administration. The mechanism of micafungin-induced hypoglycemia is not yet established. Oral administration of linear 1,3-β-D glucan has been documented to decrease blood glucose levels significantly by inhibition of expression of sodium-glucose transporter 1 (SGLT1) in intestinal mucosa.
We hypothesize that micafungin may inhibit SGLT-1 function and decrease insulin requirements in patient with T1DM.