Aims The aim was to systematically review the efficacy and safety of sodium–glucose cotransporter inhibitor (SGLT2i) as an adjunct to insulin at different follow-up durations in randomized, double-blind clinical trials in patients with type 1 diabetes. Methods We conducted a search on Medline, Embase, and the Cochrane Library for relevant studies published before May 2020. According to the duration of follow-up, the subgroup analysis included four periods: 1–4, 12–18, 24–26, and 52 weeks. In the five trials included both 24–26 and 52 weeks of follow-up, we compared the efficacy by the placebo-subtracted difference and changes in SGLT2i groups. Results Fifteen trials including 7109 participants were analyzed. The combination of SGLT2i and insulin improved hemoglobin A1c (HbA1c), fasting plasma glucose (FPG), daily insulin dose, body weight, and blood pressure, which varied greatly by different follow-ups. Compared with %HbA1c at 24–26 weeks, placebo-subtracted differences and changes in the SGLT2i groups slightly increased. SGLT2i plus insulin treatment showed no difference in the occurrence of urinary tract infections (UTIs), hypoglycemia, or severe hypoglycemia but increased the risk of genital tract infections (GTIs) in a duration-dependent manner. SGLT2i treatment was associated with a significantly higher rate of ketone-related SAEs and diabetic ketoacidosis (DKA) at 52 weeks. Conclusion SGLT2i as an add-on therapy to insulin improved glycemic control and body weight and decreased the required dose of insulin without increasing the risk of hypoglycemia. However, after 6 months the benefits of SGLT2is on glycemic control may weaken and the risks of GTIs and DKA increased.

Activities of thiamine monophosphatase (TMPase) and thiamine diphosphatase (TDPase) were measured in homogenates of brain tissue obtained at autopsy from eight alcoholic cirrhotic patients who died in hepatic coma and nine controls matched for age and for postmortem delay interval and free from neurological or psychiatric disorders, hepatic disease, or other conditions of grossly impaired nutritional status. Enzyme activities were measured by standard spectrophotometric techniques. Both TMPase and TDPase were distributed unevenly in brain with highest activities being recorded in temporal cortex. Regional correlations between TMPase and TDPase, however, were poor. TDPase activities in brain tissue from alcoholic cirrhotic patients were significantly increased in 5 of 6 brain regions, by 26 to 153% (p < 0.05). TMPase activities in alcoholic cirrhotics, on the other hand, were unchanged in all brain regions, with the exception of caudate nucleus where they were increased by 70% (p < 0.05). These findings add to the substantial body of evidence suggesting that alcoholic liver disease is associated with abnormal thiamine status and with altered thiamine neurochemistry. Increased TDP degradation resulting from increased activities of TDPase could contribute to the pathophysiological mechanisms involved in alcohol-related brain dysfunction.