Efficacy of Ipragliflozin Compared With Sitagliptin in Uncontrolled Type 2 Diabetes With Sulfonylurea and Metformin

Type 2 Diabetes Mellitus Clinical Trial

Official title:

Efficacy of Ipragliflozin Compared With Sitagliptin in Uncontrolled Type 2 Diabetes With Sulfonylurea and Metformin

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03076112
• Other study ID #: B-1612/375-004
• Status: Completed
• Phase: Phase 3
• Start date: April 25, 2017
• Est. completion date: August 31, 2022

Study information

• Verified date: October 2022
• Source: Seoul National University Bundang Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The objectives of this study are 1) to compare the effect of ipragliflozin 50 mg on glucose-lowering effect with sitagliptin 100 mg in patients with type 2 diabetes mellitus, whose HbA1c level is ≥ 7.5% with sulfonylurea and metformin, 2) to investigate changes of other metabolic and cardiovascular risk factors such as triglyceride, HDL-cholesterol, uric acid, blood pressure, and inflammatory markers, 3) to examine changes of body composition including fat and muscle mass with volume status.

Description:

The objectives of this study are to compare the effect of 50mg of ipragliflozin, a SGLT2 inhibitor, on glucose-lowering effect with 100mg of sitagliptin, a DPP4 inhibitor in patients with type 2 diabetes mellitus, whose HbA1c level is ≥ 7.5% with sulfonylurea and metformin.

We are also going to investigate changes of other metabolic and cardiovascular risk factors such as triglyceride, HDL-cholesterol, uric acid, blood pressure, and inflammatory markers.

Changes of body composition including fat and muscle mass with volume status will be also examined.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 170
• Est. completion date: August 31, 2022
• Est. primary completion date: June 30, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years to 75 Years

Eligibility

Inclusion Criteria:

• Type 2 diabetes with HbA1c 7.5% - 9.0% at screening visit

• Male or female between 20 and 75 years of age

• Patients taking sulfonylurea (glimepiride 1~8mg or gliclazide 30~120 mg or equivalent dose) and metformin (= 1000 mg or maximum tolerated dose) for more than 3 months

• BMI =23 kg/m²

• Estimated GFR = 60 ml/min/1.73m²

• Women of child bearing potential must take precautions to avoid pregnancy throughout the study and for 4 weeks after intake of the last dose and must have a negative urinary pregnancy test.

Exclusion Criteria:

• Type 1 diabetes, gestational diabetes, or diabetes with secondary cause

• Patients with acute coronary syndrome within 3 months prior to screening visit

• Patients with acute coronary syndrome within 3 months prior to screening visit

• Pregnant or breastfeeding women or reproductive-age women who refuse contraception

• Chronic hepatitis B or C (except healthy carrier of HBV), liver disease (AST/ALT > 3-fold the upper limit of normal)

• Cancer within 5 years (except squamous cell cancer, cervical cancer, thyroid cancer with appropriate treatment) except thyroid cancer or carcinoma in situ

• Other clinical trials within 30 days

• Alcohol abuse

• Contraindication to SGLT2 inhibitors or Dipeptidyl-peptidase 4 inhibitors

• Taking insulin, oral hypoglycemic agents other than metformin, sulfonylurea, and the study drugs.

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Type 2 Diabetes Mellitus

Intervention

Drug:
• Ipragliflozin
Ipragliflozin as add-on to Metformin and Sulfonylurea in patients with poorly controlled type 2 diabetes
• Sitagliptin
Sitagliptin as add-on to Metformin and Sulfonylurea in patients with poorly controlled type 2 diabetes

Locations

Country	Name	City	State
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam	Gyeonggi

Sponsors (2)

Lead Sponsor	Collaborator
Seoul National University Bundang Hospital	Astellas Pharma Korea, Inc.

Country where clinical trial is conducted

Korea, Republic of, 

References & Publications (9)

Bolinder J, Ljunggren Ö, Johansson L, Wilding J, Langkilde AM, Sjöström CD, Sugg J, Parikh S. Dapagliflozin maintains glycaemic control while reducing weight and body fat mass over 2 years in patients with type 2 diabetes mellitus inadequately controlled on metformin. Diabetes Obes Metab. 2014 Feb;16(2):159-69. doi: 10.1111/dom.12189. Epub 2013 Aug 29. — View Citation

Hedrington MS, Davis SN. Ipragliflozin , a sodium-glucose cotransporter 2 inhibitor, in the treatment of type 2 diabetes. Expert Opin Drug Metab Toxicol. 2015 Apr;11(4):613-23. doi: 10.1517/17425255.2015.1009893. Epub 2015 Feb 2. Review. — View Citation

Hermansen K, Kipnes M, Luo E, Fanurik D, Khatami H, Stein P; Sitagliptin Study 035 Group. Efficacy and safety of the dipeptidyl peptidase-4 inhibitor, sitagliptin, in patients with type 2 diabetes mellitus inadequately controlled on glimepiride alone or on glimepiride and metformin. Diabetes Obes Metab. 2007 Sep;9(5):733-45. Epub 2007 Jun 26. — View Citation

Kadokura T, Zhang W, Krauwinkel W, Leeflang S, Keirns J, Taniuchi Y, Nakajo I, Smulders R. Clinical pharmacokinetics and pharmacodynamics of the novel SGLT2 inhibitor ipragliflozin. Clin Pharmacokinet. 2014 Nov;53(11):975-88. doi: 10.1007/s40262-014-0180-z. Review. — View Citation

Macdonald FR, Peel JE, Jones HB, Mayers RM, Westgate L, Whaley JM, Poucher SM. The novel sodium glucose transporter 2 inhibitor dapagliflozin sustains pancreatic function and preserves islet morphology in obese, diabetic rats. Diabetes Obes Metab. 2010 Nov;12(11):1004-12. doi: 10.1111/j.1463-1326.2010.01291.x. — View Citation

Matthaei S, Bowering K, Rohwedder K, Grohl A, Parikh S; Study 05 Group. Dapagliflozin improves glycemic control and reduces body weight as add-on therapy to metformin plus sulfonylurea: a 24-week randomized, double-blind clinical trial. Diabetes Care. 2015 Mar;38(3):365-72. doi: 10.2337/dc14-0666. Epub 2015 Jan 15. — View Citation

Smulders RA, Zhang W, Veltkamp SA, van Dijk J, Krauwinkel WJ, Keirns J, Kadokura T. No pharmacokinetic interaction between ipragliflozin and sitagliptin, pioglitazone, or glimepiride in healthy subjects. Diabetes Obes Metab. 2012 Oct;14(10):937-43. doi: 10.1111/j.1463-1326.2012.01624.x. Epub 2012 Jun 7. — View Citation

Takasu T, Hayashizaki Y, Tahara A, Kurosaki E, Takakura S. Antihyperglycemic effect of ipragliflozin, a sodium-glucose co-transporter 2 inhibitor, in combination with oral antidiabetic drugs in mice. Clin Exp Pharmacol Physiol. 2015 Jan;42(1):87-93. doi: 10.1111/1440-1681.12317. — View Citation

Veltkamp SA, van Dijk J, Collins C, van Bruijnsvoort M, Kadokura T, Smulders RA. Combination treatment with ipragliflozin and metformin: a randomized, double-blind, placebo-controlled study in patients with type 2 diabetes mellitus. Clin Ther. 2012 Aug;34(8):1761-71. doi: 10.1016/j.clinthera.2012.06.027. Epub 2012 Jul 15. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Glycated hemoglobin	Change of HbA1c after 24 weeks' treatment	Baseline, week 12, week 24
Secondary	Glycemic target goal achievement	Glycemic target goal achievement (HbA1c < 7%) at week 24	Baseline, week 12, week 24
Secondary	Body weight	Change of body weight at week 24	Baseline, week 12, week 24
Secondary	Body fat mass	Change of body fat mass at week 24	Baseline, week 24
Secondary	Fasting plasma glucose level	Change of fasting plasma glucose level at week 24	Baseline, week 12, week 24
Secondary	Postprandial 2hr glucose level	Changes of postprandial 2hr glucose level at week 24	Baseline, week 12, week 24
Secondary	Blood Pressure	Change of systolic/diastolic blood pressure at week 24	Baseline, week 12, week 24
Secondary	Triglyceride/HDL-cholesterol ratio	Changes of triglyceride/HDL-cholesterol ratio at week 24	Baseline, week 12, week 24
Secondary	Uric acid	Changes of uric acid at week 24	Baseline, week 12, week 24
Secondary	Parathyroid hormone	Changes of parathyroid hormone at week 24	Baseline, week 12, week 24
Secondary	25-hydroxyvitamin D	Changes of 25-hydroxyvitamin D at week 24	Baseline, week 12, week 24