Efficacy and Safety Comparison of Add-on Therapy with Liraglutide, Saxagliptin and Vildagliptin, All in Combination with Current Conventional Oral Hypoglycemic Agents Therapy in Poorly Controlled Chinese Type 2 Diabetes

Abstract

To compare the efficacy and safety of adding liraglutide, saxagliptin and vildagliptin to current therapy in Chinese type 2 diabetes subjects with poor glycemic control.A 24-week, randomized, open-label, parallel clinical trial was performed. A total 178 patients completed the trial who had been randomly assigned to add-on once daily liraglutide (1.2 mg/day injected subcutaneously), to saxagliptin (5 mg once daily) or to vildagliptin (50 mg twice daily). Glycosylated hemoglobin (HbA1c) values, fasting and postprandial blood glucose (FBG and P2BG), body weight, body mass index (BMI), episodes of hypoglycemia and adverse events were evaluated.Over the 24-week treatment period, greater lowering of mean of HbA1c was achieved with 1.2 mg liraglutide (-1.50%, 95% CI [-1.67, -1.34]) than with saxagliptin (-1.23%, 95% CI [-1.36, -1.11]) and vildagliptin (-1.25%, 95% CI [-1.37, -1.13]). There was no significant between-group difference of percentages of subjects who reached a target HbA1c<7.0%, but significantly more subjects with liraglutide achieved HbA1c≤6.5% compared with saxagliptin and vildagliptin. The mean reduction of FBG value from baseline was 2.23 mmol/L with liraglutide, much greater than 1.83 mmol/L with saxagliptin (p=0.013), but similar to 2.03 mmol/L with -vildaglitpin group. As to the P2BG value, greater reductions was found with liraglutide (-4.80 mmol/L) than -3.56 mmol/L with saxagliptin (p=0.000) and -3.57 mmol/L with vildagliptin (p=0.000). Moreover, greater mean reductions of body weight and BMI with liraglutide (-6.0 kg and -2.1 kg/m(2)) were achieved than with saxagliptin and vildagliptin (both p<0.001), whereas no significant difference was found between saxagliptin and vildagliptin group. The incidence of hypoglycemia was recorded low and similar in each treatment group. Nausea was more common with liraglutide (27%) than with saxagliptin (3.2%) and vildagliptin (5.2%), but no significant between-group difference was reported in other AEs.Adding liraglutide demonstrated superiority to saxagliptin and vildagliptin for reductions of HbA1c and weight loss in Chinese subjects with T2DM who had inadequate glycemic control with conventional oral hypoglycemic agents. These findings support the add-on of liraglutide could offer notable advantages over DPP-4 inhibitors in both efficacy and safety.

Beneficial Effects of Incretin-Based Therapy on Glycemic Control, Adipokines, Insulin Sensitivity Parameters and Weight Loss in Overweight or Obese Patients With Newly Diagnosed Type 2 Diabetes: A Prospective Study

“…Our study supports previous data on liraglutide improvements in glucose control and weight reduction. HbA1c improvement was directly related to basal HbA1c in concordance with previous studies [9][10][11]. As indicated in our study, greater proportion of patients treated with liraglutide reached the target level of HbA1c < 7% than the other two agents, without accompanying an increased risk of hypoglycemia.…”

“…Many studies indicated that both GLP-1RA and DPP4i have the priority over metformin and sulfonylurea in reducing plasma glucose and body weight, and increasing insulin sensitivity. However, these studies seldom select the newly diagnosed diabetic patients as subjects, and rarely evaluate the adipokines profile [8][9][10][11]. To our knowledge, no studies have addressed the effect of liraglutide and sitagliptin treatment on plasma glycemic control, weight loss and circulating adipokines in newly diagnosed diabetic patients in daily clinical practice.…”

Efficacy and safety of autoinjected exenatide once‐weekly suspension versus sitagliptin or placebo with metformin in patients with type 2 diabetes: The DURATION‐NEO‐2 randomized clinical study

“…In this study, body weight loss was greater with exenatide QWS‐AI than with placebo but similar to body weight loss with sitagliptin. Among earlier studies comparing GLP‐1RAs with DPP‐4is, all but 2 found significantly greater body weight reductions with GLP‐1RAs over 24 to 104 weeks. The similar body weight loss seen with exenatide QWS‐AI and sitagliptin in this study may be explained by body weight loss with exenatide QWS‐AI being somewhat lower than expected.…”

“…Of 8 randomized, head‐to‐head studies comparing the GLP‐1RAs exenatide, liraglutide, albiglutide or dulaglutide with the DPP‐4i sitagliptin as add‐on therapy or monotherapy, 6 studies demonstrated significantly greater HbA1c reductions over 26 to 104 weeks with GLP‐1RAs vs sitagliptin; 1 24‐week study found no significantly different reductions with liraglutide 0.9 mg/d vs sitagliptin, and 1 26‐week study found that sitagliptin was noninferior to liraglutide 1.2 mg/d . Additionally, a 24‐week study found significantly greater HbA1c reductions with liraglutide vs saxagliptin or vildagliptin . In 7 of the 9 earlier studies, proportions of patients achieving HbA1c levels <7.0% were greater with GLP‐1RAs than DPP‐4is …”

“…Previous studies compared the efficacy and safety of GLP‐1RAs with DPP‐4is . The DURATION‐2 and DURATION‐4 studies demonstrated that exenatide QW achieved better glycaemic control than sitagliptin, both as monotherapy and in combination with metformin .…”