Clinical trial NCT01206647: Investigation of a Switch From Insulin Therapy to a Metformin & Saxagliptin Combination in Patients With Type 2 Diabetes Mellitus
Official title: Investigation of a Switch From Insulin Therapy to a Metformin & Saxagliptin Combination in Patients With Type 2 Diabetes Mellitus
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Diabetes Mellitus, Type 2
Lead sponsor: ikfe-CRO GmbH
Sponsor class: INDUSTRY
Collaborators: name: AstraZeneca
name: IKFE Institute for Clinical Research and Development
First posted: 2010-09-22
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to investigate the success rate of a switch from insulin therapy to a metformin \& saxagliptin combination in patients with type 2 diabetes mellitus.

Detailed description: The following study is based on a previous clinical trial performed at ikfe GmbH in Mainz in 2006 and 2007 (PIOswitch). \[2\] The purpose of this trial was to demonstrate that type 2 diabetes patients treated with insulin can be effectively switched to a pioglitazone/glimepiride combination without loss of glycemic control. The study was performed with 100 patients, out of whom 76 were finally successfully switched, resulting in a cheaper and more convenient therapy with indications of an improved laboratory cardiovascular risk biomarker profile (Hohberg et al., Diabetes Obes. Metab. 11:464-471, 2009). \[2\] Glimeperide is an agent with unspecific stimulating effect on the ß-cell and is considered to accelerate the progression of the disease while still controlling blood glucose. In addition, it may cause hypoglycemia. The combination of pioglitazone with glimepiride was selected, because pioglitazone requires approx. 5-6 weeks for developing its full anti-diabetic efficacy and an immediate effect on glucose was required to avoid glycemic deterioration.

It is tempting to speculate that the combination of a drug providing ß-cell protection (like saxagliptin) with a drug effectively and rapidly lowering blood glucose through a different mechanism of action (metformin) instead of unspecific ß-cell stimulation would result in an even improved outcome without risk of hypoglycemia. The purpose of this study is to investigate the success rate of a switch from insulin therapy to a metformin \& saxagliptin combination in patients with type 2 diabetes mellitus.

Eligibility criteria: Inclusion Criteria:

* Combination of OAD and basal insulin treatment (BOT) or intensified conventional therapy (ICT; \> 2 injections of basal and prandial) or conventional insulin therapy (CIT; 1 or 2 injections of basal or biphasic)
* HbA1c \< 7.5 %
* Age: 18-80 years inclusively
* Duration of insulin therapy \> 1 year
* Insulin dose \< 120 IU/day
* Fasting C-peptide \> 0.6 ng/l
* Fasting glucose ≤ 210 mg/dl
* Full legal, mental and physical ability to give informed consent
* Patient consent that the general physician will be informed of trail participation
* Experience in self measurement of blood glucose \> 1 year

Exclusion Criteria:

* Type 1 Diabetes mellitus
* History of drug or alcohol abuse within the last five years prior to screening
* History of severe or multiple allergies
* Progressive fatal disease
* History of significant cardiovascular, respiratory, gastrointestinal, hepatic (ALAT and/or ASAT \> 3 times the normal reference range), neurological, psychiatric and/or haematological disease as judged by the investigator
* Renal insufficiency or history of significant renal diseases (creatinine clearance lower than 60 ml/min determined using the Cockroft-Goult equation).
* Contra-indications for study drugs including contraindications for the rescue drugs
* Anamnestic history of hypersensitivity to the study drugs or to drugs with similar chemical structures
* Pregnancy or breast feeding
* Sexually active women of childbearing potential not consistently and correctly practicing birth control by implants, injectables, combined oral contraceptives, hormonal intrauterine devices (IUDs), sexual abstinence or vasectomised partner
* Treatment with any other investigational drug within 3 months prior to screening
* Lack of compliance or other similar reason, that according to investigator, precludes satisfactory participation in the study

Primary outcomes:
measure: percentage of patients with stable HbA1c
timeFrame: 26 ± 2 weeks (baseline to postbaseline values) at 4 week intervals
Secondary outcomes:
measure: impact of the switch on:
timeFrame: 26 ± 2 weeks (baseline to postbaseline values)
measure: impact of the switch on:
timeFrame: 26 ± 2 weeks (baseline to postbaseline values)
measure: impact of the switch on:
timeFrame: 26 ± 2 weeks (baseline to postbaseline values)
measure: impact of the switch on:
timeFrame: 26 ± 2 weeks (baseline to postbaseline values)
measure: impact of the switch on:
timeFrame: 26 ± 2 weeks (baseline to postbaseline values)
measure: impact of the switch on:
timeFrame: 26 ± 2 weeks (baseline to postbaseline values)
measure: impact of the switch on:
timeFrame: 26 ± 2 weeks (baseline to postbaseline values)
Other outcomes:
Locations:
city: Bochum
country: Germany
facility: Diabetologische Schwerpunktpraxis Dr. Lorra / Dr. Bonnermann
city: Dresden
country: Germany
facility: Zentrum für klinische Studien Dresden, GWT-TUD GmbH
city: Essen
country: Germany
facility: Gemeinschaftspraxis Partner der Gesundheit
city: Mainz
country: Germany
facility: IKFE Institute for Clinical Research and Development
city: Münster
country: Germany
facility: Zentrum für Diabetes und Gefäßerkrankungen
city: Neuwied
country: Germany
facility: Diabetes Zentrum Neuwied
city: Potsdam
country: Germany
facility: ikfe Studiencenter Potsdam GmbH
Study officials:
affiliation: IKFE Institute for Clinical Research and Development
name: Andreas Pfützner, Prof.Dr.Dr.
role: PRINCIPAL_INVESTIGATOR
References: