Efficacy and safety of sitagliptin/metformin fixed-dose combination compared with glimepiride in patients with type 2 diabetes: A multicenter randomized double-blind study

J Diabetes. 2017 Apr;9(4):412-422. doi: 10.1111/1753-0407.12432. Epub 2016 Aug 8.

Abstract

Background: Early initiation of combination therapy using antihyperglycemic agents is recommended for treating type 2 diabetes (T2D). The present multicenter double-blind randomized parallel-group study examined the efficacy and safety of a sitagliptin and metformin fixed-dose combination (Sita/Met) compared with glimepiride in T2D patients as initial treatment.

Methods: Type 2 diabetes patients (aged ≥18 years) were randomized to Sita/Met or glimepiride for 30 weeks after a wash-off run-in period. The primary endpoint was change from baseline (CFB) in HbA1c. Secondary endpoints included the proportion of patients achieving target goal (HbA1c < 7.0 % [53 mmol/mol]) and CFB in fasting plasma glucose (FPG). Safety assessments comprised weight gain from baseline and the incidence of adverse events (AEs).

Results: In total, 292 patients were randomized to Sita/Met (n = 147) or glimepiride (n = 145). After 30 weeks, Sita/Met demonstrated superiority over glimepiride in reducing HbA1c (-1.49 % vs -0.71 %, respectively; between-group difference - 0.78 %; P < 0.001). A significantly higher proportion of patients achieved the target goal with Sita/Met (81.2 %) than with glimepiride (40.1 %; P < 0.001). Greater reduction in FPG occurred with Sita/Met than with glimepiride (least-squares mean difference - 23.5 mg/dL; P < 0.001). Both drugs were generally well tolerated. Hypoglycemia events and weight gain were significantly lower in patients with Sita/Met than with glimepiride (5.5 % vs 20.1 % and -0.83 vs +0.90 kg, respectively; both P < 0.001). No serious drug-related AEs or deaths were reported.

Conclusions: Compared with glimepiride, Sita/Met as an initial treatment led to significantly greater improvements in glycemic control and body weight changes, with a lower incidence of hypoglycemia, over 30 weeks.

Keywords: glimepiride; hypoglycemia; metformin; sitagliptin phosphate; 二甲双胍; 低血糖; 格列美脲; 磷酸西格列汀.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Blood Glucose / metabolism
  • Body Weight / drug effects
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diarrhea / chemically induced
  • Double-Blind Method
  • Drug Therapy, Combination
  • Dyspepsia / chemically induced
  • Female
  • Glycated Hemoglobin / metabolism
  • Humans
  • Hypoglycemic Agents / adverse effects
  • Hypoglycemic Agents / therapeutic use
  • Infections / chemically induced
  • Male
  • Metformin / adverse effects
  • Metformin / therapeutic use*
  • Middle Aged
  • Nausea / chemically induced
  • Sitagliptin Phosphate / adverse effects
  • Sitagliptin Phosphate / therapeutic use*
  • Sulfonylurea Compounds / adverse effects
  • Sulfonylurea Compounds / therapeutic use*
  • Treatment Outcome

Substances

  • Blood Glucose
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Sulfonylurea Compounds
  • glimepiride
  • Metformin
  • Sitagliptin Phosphate