Performance Under SGLT-2-Inhibitors in Humans (PUSH)

Early Performance in Patients With Type-II-Diabetes Mellitus Under New Treatment With SGLT-2-Inhibitors Compared to Control Groups.

The PUSH Study is conceived to investigate the early effects of SGLT-2-Inhibitors on the physical performance of patients with Type-II-Diabetes mellitus compared to patients under other therapy regimes. Patients shall be divided into 3 groups: I - Patients with type II diabetes mellitus under new treatment with an SGLT2-Inhibitor. II - Patients with type II diabetes mellitus without SGLT-2- Inhibitor medication. III - Patients without type II diabetes mellitus but with similar comorbidities to the previous groups.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 2

Detailed Description

SGLT-2-Inhibitors have been shown to improve cardiovascular outcomes in patients with type II diabetes mellitus. Present evidence shows this effect to be not directly related to better serum glucose levels because the effect was measurable within several days of initiation of the treatment.

In a prospective single-centre double-blinded comparative observational study, other aspects of the effect of SGLT-2-Inhibitors shall be analyzed from patient registry, particularly the physical performance of patients under new treatment with SGLT-2-Inhibitors. Patient consent will be sort for the analysis of clinical data during the duration of stay.

Patients included in the registry suitable for analysis shall be divided into 3 groups: I - Patients with type II diabetes mellitus under new treatment with an SGLT2-Inhibitor. II - Patients with type II diabetes mellitus without SGLT-2- Inhibitor medication. III - Patients without type II diabetes mellitus but with similar comorbidities to the previous groups.

• Study Type: Observational
• Enrollment (Actual): 450

Contacts and Locations

Study Locations

• Switzerland
  • Valais
    • Crans-Montana, Valais, Switzerland, 3963
      • Berner Klinik Montana

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Ambulatory patients above the age of 40 who provide informed consent.

Description

Inclusion Criteria:

• informed consent
• ambulatory patients

Exclusion Criteria:

• relevant limitations in movement

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
Patients with T2DM under new therapy with SGLT-2-Inhibitors; Patients with T2DM under new therapy with SGLT-2-Inhibitors (Empagliflozin 10 mg per day, Dapagliflozin 10 mg per day, Canagliflozin 100 mg per day) at baseline.
Patients with T2DM without SGLT-2-Inhibitors.; Patients with T2DM without therapy with SGLT-2-Inhibitors (Empagliflozin 10 mg per day, Dapagliflozin 10 mg per day, Canagliflozin 100 mg per day) at baseline.
Patients without T2DM manifesting similar comorbidities; Patients without T2DM manifesting similar comorbidities (Haemoglobin value, renal function, similar body mass index, cardiovascular disease profile)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Distance	Change in distance covered in metres (m).	28 days
Rate of perceived exertion	Change in modified Borg Scale as subjective assessment of moderate intensity physical activity ( Range 0 - 10)	28 days
Saturation	Change in saturation after exertion, expressed in %	28 days
Heart rate after exertion	Change in heart rate after exertion, expressed as bpm	28 days
Maximum oxygen uptake	Change in predicted VO2 max using distance covered in 6 minute walk test as follows 4.948 0.023*Mean 6 MWD (meters)	28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Muscle anatomy	Change in muscle architecture parameter (MAP) measured as the mid-thigh diameter of the medial vastus muscle using B-mode sonography in centimètres (cm).	28 days
Muscle physiology	Muscle strength measured as hand grip in Newton using a hand dynamometer in kg	28 days
Biochemical	change in routine laboratory parameter related to muscle status using measurements of creatinine kinase in serum, CK in U/l	28 days
Subjective Assessment	Change in fatigue using a Fatigue Score questionnaire (FSMC) as assessed by patient (Range 20 - 100).	28 days
Echocardiographic parameters (function)	Change in left ventricular function using doppler readings of LVOT: LVEF using Dusmenil Formula SV/LVEDV expressed in %.	28 days
Muscle anatomy (echogenicity)	Change in muscle architecture parameter (MAP) measured as the mid-thigh echogenicity of the lateral vastus muscle, using image J software, arbitary units (AU)	28 days
Biochemical (metabolic function)	change in routine laboratory parameter related to metabolic function: Uric acid in serum, expressed in micromol/l	28 days
Body constitution (BMI)	change in body mass index measured as weight/height x height expressed in kg/m2	28 days
Body constitution (Hip circumference)	change in hip circumference measured at the maximum posterior protrusion of the buttocks in cm	28 days
Body constitution (Muscle mass predicted I)	change in muscle mass predicted using the Baumgartner equation 0.2487(BM) + 0.0483(ST)-0.1584(GQUAD) +0.0732(HGS) +2.5843(SEX) + 5.8828 in kg	28 days
Body constitution (Muscle mass predicted II)	change in muscle mass predicted using the muscle thickness of the forearm (4.89xMT-Ulna(cm)xHeight(m)-9.15) in kg	28 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Echocardiographic parameters (GLS)	Change in left ventricular systolic function using global longitudinal strain Imaging: GLS expressed as GLS avg in minus %.	28 days
Biochemical (NTproBNP)	change in routine laboratory parameter related to cardiac function using measurements of NTproBNP in ng/l	28 days
Echocardiographic parameters (LVEDV)	Change in left ventricular structure using B-mode Imaging: LVEDV in mm	28 days
Echocardiographic parameters (LAVI)	Change in left atrial structure structure using Biplane method: LAVI in ml/m2	28 days
Echocardiographic parameters (LV Massindex)	Change in left ventricular structure using B-mode Imaging: LV Massindex in g/m2	28 days
Echocardiographic parameters (E/e' avg)	Change in left ventricular diastolic function using Mitral inflow E velocity as obtained by pulsed-wave (PW) Doppler expressed E/e' avg ratio	28 days

Collaborators and Investigators

• Sponsor: Berner Klinik Montana
• Investigators: Principal Investigator: Devine S Frundi, MD, Berner Klinik Montana

Publications and helpful links

General Publications

• Frundi DS, Kettig E, Popp LL, Hoffman M, Dumartin M, Hughes M, Lamy E, Fru YJW, Bano A, Muka T, Wilhelm M. Physical performance and glycemic control under SGLT-2-inhibitors in patients with type 2 diabetes and established atherosclerotic cardiovascular diseases or high cardiovascular risk (PUSH): Design of a 4-week prospective observational study. Front Cardiovasc Med. 2022 Jul 22;9:907385. doi: 10.3389/fcvm.2022.907385. eCollection 2022.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2018
• Primary Completion (Actual): September 30, 2020
• Study Completion (Actual): September 30, 2020

Study Registration Dates

• First Submitted: January 23, 2018
• First Submitted That Met QC Criteria: January 30, 2018
• First Posted (Actual): February 5, 2018

Study Record Updates

• Last Update Posted (Actual): October 8, 2020
• Last Update Submitted That Met QC Criteria: October 6, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Keywords: SGLT-2-Inhibitor, Empagliflozin, Canagliflozin, Dapagliflozin
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2
• Other Study ID Numbers: Bernerklinik

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided
• IPD Plan Description: Results of the study for academic purposes for trainees to get an academic degree within Switzerland.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No