Effect of Dapagliflozin on Glycemic Variability in Patients with Type 2 Diabetes under Insulin Glargine Combined with Other Oral Hypoglycemic Drugs

Abstract

Aim. To evaluate the effect of an inhibitor of sodium-glucose cotransporter 2 (SGLT-2 inhibitor, dapagliflozin) on glycemic variability in type 2 diabetes mellitus (T2D) under insulin glargine combined with oral hypoglycemic drugs, using a continuous glucose monitoring system (CGMS). Methods. This prospective, self-controlled, single-center clinical trial recruited 36 patients with T2D under combined insulin glargine and oral hypoglycemic drugs. General clinical data were collected. Fasting blood glucose (FBG), postprandial blood glucose (PBG), glycosylated hemoglobin (HbA1c), and C-peptide levels were assessed before and four weeks of dapagliflozin (10 mg per day) treatment. Blood glucose was monitored for 72 hours before and after treatment using CGMS. Results. After treatment with dapagliflozin, FBG decreased from 6.74 ± 1.78 to 5.95 ± 1.13 mmol/L ( p < 0.05 ); PBG decreased from 13.04 ± 2.99 to 10.92 ± 3.26 mmol/L ( p < 0.05 ); HbA1c decreased from 7.37 ± 0.96 % to 6.94 ± 0.80 % . The proportion of patients with HbA 1 c < 7 % increased from 27.8% to 58.3%, and the proportion of patients with HbA 1 c < 7 % and without level 2 hypoglycemia increased from 27.8% to 55.6% ( p < 0.05 ). CGMS data showed reduction of the 24 h MBG, MAGE, time-above-range (TAR, >10 mmol/L), high blood glucose index (HBGI), glucose management indicator (GMI), and incremental area under the curve of the glucose level more than 10 mmol/L ( AUC > 10 ) and an increase of time-in-range (TIR, 3.9-10 mmol/L) with treatment. Homeostasis model assessment for pancreatic beta-cell function (HOMA-beta) increased significantly with treatment ( p < 0.05 ), and fewer insulin doses were required after the treatment, without increasing in hypoglycemia and urinary tract infection. Further, a stratified analysis showed that patients with higher pretreatment HbA1c and waist-to-hip ratio (WHR) had greater improvement in glycemic control. Conclusion. Dapagliflozin may reduce blood glucose levels, ameliorate glycemic variability, and improve pancreatic beta-cell function in patients with T2D under insulin glargine combined with other oral hypoglycemic drugs, especially in those with poor glucose control and abdominal obesity.

Acute Glycemic Variability and Early Outcomes After Cardiac Surgery: A Meta-Analysis

“…Furthermore, although multivariate regression analysis was used in all of the included studies, we could not exclude the possibility that there may be residual factors confounding the association, such as the potential influences of different antidiabetic medications and glycemic control strategies. A recent study showed that dapagliflozin (one of the sodium-glucose cotransporter-2 inhibitors) may ameliorate glycemic variability in patients with type 2 diabetes [41], while dapagliflozin has also been shown to benefit cardiac function [42]. Since poor cardiac function has been recognized as an independent risk factor of poor in-hospital outcome of patients after cardiac surgery [43], use of antidiabetic such as dapagliflozin may therefore confound the relationship between acute GV and in-hospital outcome of these patients.…”

Effect of Add-On Therapy of Sodium-Glucose Cotransporter 2 Inhibitors and Dipeptidyl Peptidase 4 Inhibitors on Adipokines in Type 2 Diabetes Mellitus

“…The therapy with SGLT2 inhibitor might be more suitable in type 2 diabetic patients with visceral obesity and poor glycemic control. SGLT2 inhibitor also has a positive influence on glycemic control without the appearance of hypoglycemia [ 42 ]. Our study found that the add-on therapy of both SGLT2 inhibitors and DPP4 inhibitors is associated with a significant beneficial effect (P < 0.001) on FPG, PPBG and HbA1c levels in type 2 diabetic patients.…”

Association between Variability of Metabolic Risk Factors and Cardiometabolic Outcomes

“…In addition, adding dapagliflozin to long-acting insulin and other OHA ameliorated GV in a study including 36 subjects from a Chinese hospital [53]. However, a recently published placebo-controlled, randomized study with 84 Korean patients reported that adding dapagliflozin to basal insulin plus OHA did not show superiority to placebo in terms of GV [54].…”

“…As for SGLT2 inhibitors, despite limited evidence of the superiority of GV to other OHA, Nomoto et al [ 52 ] showed similar GV between dapagliflozin plus glargine and DPP4 inhibitor plus glargine. In addition, adding dapagliflozin to long-acting insulin and other OHA ameliorated GV in a study including 36 subjects from a Chinese hospital [ 53 ]. However, a recently published placebo-controlled, randomized study with 84 Korean patients reported that adding dapagliflozin to basal insulin plus OHA did not show superiority to placebo in terms of GV [ 54 ].…”