Rationale and design of the EMPA-ELDERLY trial: a randomised, double-blind, placebo-controlled, 52-week clinical trial of the efficacy and safety of the sodium-glucose cotransporter-2 inhibitor empagliflozin in elderly Japanese patients with type 2 diabetes

Daisuke Yabe, Kosuke Shiki, Keiko Suzaki, Thomas Meinicke, Yutaro Kotobuki, Kenichiro Nishida, Douglas Clark, Atsutaka Yasui, Yutaka Seino, Daisuke Yabe, Kosuke Shiki, Keiko Suzaki, Thomas Meinicke, Yutaro Kotobuki, Kenichiro Nishida, Douglas Clark, Atsutaka Yasui, Yutaka Seino

Abstract

Introduction: Elderly people (≥65 years) with type 2 diabetes mellitus (T2DM) are becoming increasingly prevalent, notably in Japan. As cardiovascular (CV) risk increases with age and sodium-glucose cotransporter-2 (SGLT2) inhibitors reduce CV risk, elderly patients with T2DM are increasingly likely to be prescribed these glucose-lowering drugs. There is controversy surrounding the effects of SGLT2 inhibitors on muscle mass, particularly in elderly patients for whom loss of muscle is especially undesirable; however, robust evidence on this important issue is lacking. Consequently, we have designed a clinical trial of the SGLT2 inhibitor empagliflozin in elderly Japanese patients with T2DM (Empagliflozin in Elderly T2DM Patients (EMPA-ELDERLY)) to assess its effects on body composition as well as glycaemic control. EMPA-ELDERLY will be the first randomised clinical trial of an SGLT2 inhibitor in elderly patients with T2DM to evaluate effects on skeletal muscle mass, muscle strength and physical performance concurrently.

Methods and analysis: EMPA-ELDERLY is a randomised, double-blind, placebo-controlled, parallel-group clinical trial to be conducted in Japan. Patients with T2DM aged ≥65 years are eligible if they are Japanese with a body mass index of ≥22 kg/m2 and glycated haemoglobin (HbA1c) levels from ≥7.0% to ≤10.0% from either diet and exercise alone or treatment with oral glucose-lowering drugs. Approximately 128 participants will be randomised 1:1 to once per day, oral, double-blind treatment with empagliflozin 10 mg or matching placebo for 52 weeks. The primary endpoint is the change in HbA1c level from baseline at week 52. Secondary endpoints include changes from baseline to 52 weeks in body composition, including muscle mass and body fat, measured by bioelectrical impedance analysis, as well as skeletal muscle index, grip strength and time in the five-time chair stand test. Other endpoints include changes in patient-reported outcomes (including quality of life), cognitive function and safety.

Ethics and dissemination: We will submit the trial results to conferences and peer-reviewed journals.

Trial registration number: NCT04531462.

Keywords: Clinical trials; Diabetes & endocrinology; GERIATRIC MEDICINE; General diabetes.

Conflict of interest statement

Competing interests: DY has received consulting or speaker fees from Astellas Pharma Inc., Dainippon Sumitomo Pharma Co., Ltd., Eli Lilly Japan K.K., MSD K.K., Novo Nordisk Pharma Ltd., Nippon Boehringer Ingelheim Co. Ltd., Ono Pharmaceutical Co. Ltd., Taisho Pharmaceutical Co. Ltd., and Takeda Pharmaceutical Company Limited and clinically commissioned/joint research grants from Taisho Pharmaceutical Co. Ltd., Ono Pharmaceutical Co. Ltd., Novo Nordisk Pharma Ltd., Arklay Co. Ltd. and Nippon Boehringer Ingelheim Co. Ltd. KSh, KSu, YK, KN and AY are employees of Nippon Boehringer Ingelheim Co. Ltd. TM and DC are employees of Boehringer Ingelheim International GmbH. YS has received lecture fees from MSD, K.K., Kao, Taisho, Boehringer Ingelheim, Taisho Toyama, Takeda, Becton Dickinson and Novo Nordisk; and research support from Terumo, Bayer, Boehringer Ingelheim, Ono, Sumitomo Dainippon, Taisho Toyama and Novo Nordisk.

© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1
Figure 1
Design of the EMPA-ELDERLY (Empagliflozin in Elderly T2DM Patients) trial.

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