Empagliflozin treatment effects across categories of baseline HbA1c, body weight and blood pressure as an add-on to metformin in patients with type 2 diabetes

Diabetes Obes Metab. 2021 Feb;23(2):425-433. doi: 10.1111/dom.14234. Epub 2020 Nov 20.

Abstract

Aim: To investigate the association of different categories of baseline cardio-metabolic risk factors on the treatment effects of empagliflozin 10 and 25 mg when added as second-line therapy to metformin in patients with type 2 diabetes (T2D).

Materials and methods: Patients aged 18 years or older with HbA1c 7.0%-10.0% were included. Analysis of covariance compared change from baseline to weeks 24 and 76 in HbA1c, body weight (BW) and systolic blood pressure (SBP) by respective baseline categories (HbA1c <8.5/≥8.5%; BW <80/80-90/>90 kg, SBP <130/130-140/>140 mmHg). Analyses were also conducted with a model using continuous covariates of cardio-metabolic factors.

Results: In total, 637 patients (56.7% males; mean [SD] age 55.7 [9.9] years, HbA1c 7.9% [0.9%], BW 81.2 [18.8] kg, SBP 129.4 [14.6] mmHg) received one or more dose of either empagliflozin 10 mg (n = 217) or 25 mg (n = 213), or placebo (n = 207). At both time points, empagliflozin 10/25 mg versus placebo significantly (P < .0001) reduced HbA1c and BW, with greater reductions in HbA1c at higher baseline HbA1c (P interaction week 24/76 categorical and continuous models: .0290/.1431 and .0004/.0042, respectively) and in BW (P interaction .1340/.0012 and .0202/<.0001, respectively). Both empagliflozin doses also significantly lowered SBP versus placebo at both time points, with similar efficacy by subgroups of baseline SBP. Adverse events were consistent with the established empagliflozin safety profile across treatment groups.

Conclusions: Empagliflozin, as add-on to metformin, decreases HbA1c and BW, particularly in patients with higher HbA1c and BW baseline values, and effectively lowers SBP.

Trial registration: ClinicalTrials.gov NCT01159600 NCT01289990.

Keywords: SGLT2 inhibitor; body weight; empagliflozin; glycaemic control; metformin; type 2 diabetes.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Benzhydryl Compounds / adverse effects
  • Blood Pressure
  • Body Weight
  • Diabetes Mellitus, Type 2* / drug therapy
  • Double-Blind Method
  • Drug Therapy, Combination
  • Female
  • Glucosides
  • Glycated Hemoglobin A / analysis
  • Humans
  • Hypoglycemic Agents / therapeutic use
  • Male
  • Metformin* / therapeutic use
  • Middle Aged
  • Treatment Outcome

Substances

  • Benzhydryl Compounds
  • Glucosides
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Metformin
  • empagliflozin

Associated data

  • ClinicalTrials.gov/NCT01159600
  • ClinicalTrials.gov/NCT01289990