An overview of the effect of sodium glucose cotransporter 2 inhibitor monotherapy on glycemic and other clinical laboratory parameters in type 2 diabetes patients

Abstract

ObjectivesWe aimed to determine the effect of sodium glucose cotransporter 2 (SGLT2) inhibitor monotherapy on glycemic and other clinical laboratory parameters versus other antidiabetic medications or placebo therapy in patients with type 2 diabetes mellitus. In addition, we aimed to investigate the risk of diabetic ketoacidosis associated with SGLT2 inhibitor therapy and evaluate its weight-sparing ability.DesignMeta-analysis.Materials and methodsPubMed and MEDLINE were searched to identify eligible studies up to December 2015. Randomized controlled trials that assessed the efficacy and safety of SGLT2 inhibitor monotherapy versus placebo therapy or active control were considered. The Cochrane Collaboration Risk of Bias Tool was used to evaluate quality and bias. The mean difference was used to evaluate the glycemic and other clinical laboratory parameters for SGLT2 inhibitor intervention versus control by drugs or placebo. Similarly, the risk ratio was used to assess adverse events, and the I2 was used to evaluate heterogeneity.ResultsSGLT2 inhibitors significantly decreased glycated hemoglobin (HbA1c) (P<0.001), weight (P<0.001), and the low-density lipoprotein/high-density lipoprotein ratio (P=0.03) compared with placebo therapy. No statistically significant changes were found in fasting plasma glucose, 2-hour postprandial glucose, or lipid parameters. Significant changes in the uric acid level were found for SGLT2 inhibitors versus placebo therapy (P=0.005) or active control (P<0.001). Although no significant change in levels of ketones occurred (P=0.93), patients receiving SGLT2 inhibitors were at greater risk of increased ketone bodies. Events suggestive of urinary tract infection and pollakiuria presented the greatest risk for patients receiving SGLT2 inhibitors versus active control or placebo therapy.ConclusionSGLT2 inhibitors significantly decreased HbA1c, body weight, and the low-density lipoprotein/high-density lipoprotein ratio and were found to be safe and well tolerated in type 2 diabetes mellitus patients. Further randomized control trials are required to establish their risk for ketoacidosis.

The effects of licogliflozin, a dual SGLT1/2 inhibitor, on body weight in obese patients with or without diabetes

“…In patients with obesity, licogliflozin was associated with a 5.7% reduction in placebo-adjusted body weight following 12 weeks of treatment. This is in contrast to the 1%-2% reduction in weight that was observed over 12 weeks of treatment with selective SGLT2 inhibition, 37 and it is in line with the clinically meaningful weight loss of >5% (at 12 months) that is required by the FDA for approval of new drugs. 8 FDA analysis of clinical trial data revealed that a 12-week weight loss of >5% achieved with lorcaserin of phenterminetopiramate was predictive of meaningful weight loss at 12 months following treatment, 38 suggesting that the weight loss seen with licogliflozin by 12 weeks is promising.…”

“…inhibition, 37 and it is in line with the clinically meaningful weight loss of >5% (at 12 months) that is required by the FDA for approval of new drugs. 8 post-prandial glucose (incremental AUC reduced by >90%).…”

Sotagliflozin: a dual sodium‐glucose co‐transporter‐1 and ‐2 inhibitor for the management of Type 1 and Type 2 diabetes mellitus

“…In terms of safety, all SGLT2 inhibitors have been associated with an elevated risk of genitourinary infections as a result of increased glycosuria . More seriously, the risk of diabetic ketoacidosis (DKA) has also been seen to increase , with an FDA warning applicable to all drugs of this class .…”

“…However, heterogeneous study designs and variable participant characteristics mean that results should be interpreted with caution. In terms of safety, all SGLT2 inhibitors have been associated with an elevated risk of genitourinary infections as a result of increased glycosuria [28,31]. More seriously, the risk of diabetic ketoacidosis (DKA) has also been seen to increase [25,[32][33][34], with an FDA warning applicable to all drugs of this class [35][36][37].…”

Natural products with SGLT2 inhibitory activity: Possibilities of application for the treatment of diabetes

“…Studies indicate that sotagliflozin could reduce insulin resistance and may be a valuable adjunct for metformin and DPP‐4 inhibitors in patients with T2DM. Additional benefits include reductions in weight, systolic blood pressure, and appetite, and benefits for individuals with reduced kidney function were also noted (Rosenstock et al, ; Wang, Hu, Liu, & Wang, ). Sotagliflozin has entered into phase III trials to treat patients with T1DM and has shown promising outcomes (DANNE et al, ).…”