Effects of 5 Weeks Treatment With Dapagliflozin in Type 2 Diabetes Patients on How the Hormone Insulin Acts on Sugar Uptake in Muscles.

NCT03338855 | Completed Phase 4 Results

• 2 other identifiers: D1690C000472016-003991-27
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to investigate the effects of 5 weeks treatment with dapagliflozin in type 2 diabetes patients on how the hormone insulin acts on sugar uptake in muscles.

Conditions

Diabetes Mellitus, Type 2; Skeletal Muscle Insulin Sensitivity

Keywords

T2DM, insulin resistance, skeletal muscle, mitochondria, dapagliflozin

Outcome Measures

Primary Outcomes (1)

• Corrected Glucose Disposal Rate (cGDR) Measured as Change in Rate of Disposal (Delta RD) Basal vs High Insulin After 5 Weeks of Treatment

  Skeletal muscle insulin sensitivity was measured as cGDR (referred to as delta RD \[basal vs high insulin\]) using a 2-step 5.5 hour euglycemic hyperinsulinemic clamp (EHC) procedure in combination with infusion of D-glucose (6,6-D2) glucose. Delta RD (basal vs high insulin) was corrected for urinary glucose excretion and measured at the end of Treatment Periods 1 and 2.

  At end (Week 5) of Treatment Periods 1 and 2

Other Outcomes (7)

• Change in Endogenous Glucose Production (EGP) After 5 Weeks of Treatment

  At end (Week 5) of Treatment Periods 1 and 2

• Change in Respiratory Exchange Ratio (RER) From Fasted State to Insulin Stimulated State After 5 Weeks of Treatment

  At end (Week 5) of Treatment Periods 1 and 2

• 24-Hour RER After 5 Weeks of Treatment

  At end (Week 5) of Treatment Periods 1 and 2

Study Arms (2)

Dapagliflozin

ACTIVE COMPARATOR

Patients will receive dapagliflozin 10 mg in tablet for a maximum of 40 days based on randomization sequence in Period 1. Patients that received 10 mg dapagliflozin in the first treatment period will receive matching placebo in the second treatment period for a maximum of 40 days.

Drug: Dapagliflozin

Placebo matching to dapagliflozin

PLACEBO COMPARATOR

Patients will receive matching placebo in tablet for a maximum of 40 days based on randomization sequence. Patients who received placebo in the first treatment will receive 10 mg dapagliflozin in the second treatment period, for a maximum of 40 days

Drug: Dapagliflozin

Interventions

Dapagliflozin DRUG

The study consist of 5 weeks treatment period 1, 6-8 weeks wash-out period and 5 weeks treatment period 2. The patient will be administered dapagliflozin 10 mg during Period 1 or Period 2.

Dapagliflozin; Placebo matching to dapagliflozin

Eligibility Criteria

• Age: 40 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may not qualify if:

• Involvement in the planning and conduct of the study (applies to both AstraZeneca staff and staff at third party vendor or at the investigational sites).
• Previous enrolment in the present study or participation in another clinical study with an investigational product during the last 3 months or as judged by the Investigator.
• History of or presence of any clinically significant disease or disorder including a recent (\< 3 months) cardiovascular event which, in the opinion of the Investigator, may either put the patient at risk because of participation in the study or influence the results or the patient's ability to participate in the study.
• Clinical diagnosis of Type 1 diabetes, maturity onset diabetes of the young, secondary diabetes or diabetes insipidus.
• Unstable/rapidly progressing renal disease or estimated Glomerular Filtration Rate \< 60 mL/min (Cockcroft-Gault formula).
• Clinically significant out of range values of serum levels of either alanine aminotransferase (ALT), aspartate aminotransferase (AST) or alkaline phosphatase (ALP) in the Investigator's opinion.
• Contraindications to dapagliflozin according to the local label.
• Use of antidiabetic drugs other than metformin within 3 months prior to screening.
• Weight gain or loss \> 5 kg in the last 3 months, ongoing weight-loss diet (hypocaloric diet) or use of weight loss agents.
• History of drug abuse or alcohol abuse in the past 12 months.
• Any clinically significant abnormalities in clinical chemistry, hematology or urinalysis or other condition the Investigator believes would interfere with the patient's ability to provide informed consent, comply with study instructions, or which might confound the interpretation of the study results or put the patient at undue risk.
• Plasma donation within one month of screening or any blood donation/blood loss \> 500 mL within 3 months prior to screening or during the study.
• Anemia defined as Hemoglobin (Hb) \< 115 g/L (7.1 mM) in women and \< 120 g/L (7.5 mM) in men.
• Use of anti-coagulant treatment such as heparin, warfarin, platelet inhibitors, thrombin and factor X inhibitors.
• Use of medication such as oral glucocorticoids, anti-estrogens or other medications that are known to markedly influence insulin sensitivity.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (1)

Research Site

Maastricht, 6229 ER, Netherlands

Location

Related Publications (2)

• Op den Kamp YJM, Gemmink A, de Ligt M, Dautzenberg B, Kornips E, Jorgensen JA, Schaart G, Esterline R, Pava DA, Hoeks J, Schrauwen-Hinderling VB, Kersten S, Havekes B, Koves TR, Muoio DM, Hesselink MKC, Oscarsson J, Phielix E, Schrauwen P. Effects of SGLT2 inhibitor dapagliflozin in patients with type 2 diabetes on skeletal muscle cellular metabolism. Mol Metab. 2022 Dec;66:101620. doi: 10.1016/j.molmet.2022.101620. Epub 2022 Oct 21.

  PMID: 36280113 DERIVED

• Op den Kamp YJM, de Ligt M, Dautzenberg B, Kornips E, Esterline R, Hesselink MKC, Hoeks J, Schrauwen-Hinderling VB, Havekes B, Oscarsson J, Phielix E, Schrauwen P. Effects of the SGLT2 Inhibitor Dapagliflozin on Energy Metabolism in Patients With Type 2 Diabetes: A Randomized, Double-Blind Crossover Trial. Diabetes Care. 2021 Jun;44(6):1334-1343. doi: 10.2337/dc20-2887. Epub 2021 Apr 15.

  PMID: 33858855 DERIVED

Related Links

• Redacted CSP
• Redacted SAP

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Insulin Resistance

Interventions

dapagliflozin

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Hyperinsulinism

Results Point of Contact

• Title: Global Clinical Lead
• Organization: AstraZeneca

information.center@astrazeneca.com

+1 877-240-9479

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 7, 2017
• First Posted: November 9, 2017
• Study Start: March 5, 2018
• Primary Completion: November 4, 2019
• Study Completion: November 4, 2019
• Last Updated: January 15, 2021
• Results First Posted: January 15, 2021

Record last verified: 2021-01

Locations

NL (1)