Safety and Efficacy of Bexagliflozin Compared to Sitagliptin as Add-on Therapy to Metformin in Type 2 Diabetes Subjects
Condition: Type 2 Diabetes Mellitus
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Intervention: Bexagliflozin; Sitagliptin; Placebo for sitagliptin; Placebo for bexagliflozin
Intervention description: tablets containing 20 mg bexagliflozin; tablets containing 100 mg sitagliptin; inactive tablets to match the appearance of sitagliptin tablets; inactive tablets to match the appearance of bexagliflozin tablets
Intervention MeSH terms: Sitagliptin Phosphate; Bexagliflozin
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 386.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to investigate the effect of bexagliflozin compared to
      sitagliptin as an add-on therapy to metformin in lowering hemoglobin A1c (HbA1c) levels in
      subjects with type 2 diabetes mellitus (T2DM).
    

Eligibility criteria:

        Each subject was required to meet the following criteria at the time of enrollment to be
        eligible for the study:

          1. To have been male or female adults ≥ 18 years of age.

          2. To have been negative on the urine pregnancy test and agreed to abstain from coitus or
             use contraception during the entire study if a subject was female of childbearing
             potential.

          3. To have had a diagnosis of T2DM with HbA1c levels between 7.0% and 11% (inclusive) at
             the time of screening.

          4. To have been treated with a stable dose of ≥ 1500 mg/day metformin only along with
             diet and exercise counseling for at least 8 weeks at the time of screening.

          5. To have had a BMI ≤ 45 kg per m2 at the time of screening.

          6. To have been taking stable doses of treatment for dyslipidemia and/or hypertension for
             30 days if applicable.

          7. To have been willing and able to return for all clinic visits and to complete all
             study-required procedures.

          8. To have adhered to the investigational product administration requirements as
             evidenced by missing no more than 1 day of run-in medications.

        Potential subjects who exhibited any of the following characteristics were to be excluded
        from the study:

          1. Diagnosis of type 1 diabetes mellitus or maturity-onset diabetes of the young (MODY)

          2. Hemoglobinopathy that affected HbA1c measurement

          3. Any contraindication to the safe use of DPP-4 therapy or sitagliptin, including known
             hypersensitivity reaction

          4. History of pancreatitis

          5. Genitourinary tract infection within 6 weeks of screening or history of ≥ 3
             genitourinary infections requiring treatment within 6 months from the time of
             screening

          6. Cancer, active or in remission, for < 3 years

          7. History of alcohol or illicit drug abuse in the past 2 years

          8. Triglycerides > 500 mg dL-1 at Visit V1

          9. Evidence of abnormal liver function tests (total bilirubin or alkaline phosphatase >
             1.5 x upper limit of normal (ULN) with the exception of isolated Gilbert's syndrome);
             or alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2.5 x ULN

         10. Estimated GFR, as calculated by the modification of diet in renal disease study
             equation (MDRD), < 60 mL min-1 per 1.73 m2 at the time of screening.

         11. Uncontrolled hypertension (SBP > 160 mm Hg or diastolic BP > 95 mm Hg) at Visit V1

         12. Life expectancy < 2 years

         13. History of MI, unstable angina, stroke or hospitalization for heart failure within 3
             months at the time of screening

         14. History of treatment with an investigational drug within 30 days or within 7
             half-lives of the investigational drug, whichever is longer

         15. Previous treatment with bexagliflozin or EGT0001474 study drug

         16. Currently or within 3 months of taking any SGLT2 inhibitor

         17. Currently participating in another interventional trial

         18. Prior renal transplantation or evidence of nephrotic syndrome (defined as a urine
             albumin-to-creatinine ratio (UACR) > 1500 mg g-1 at the time of screening).

         19. Any condition, disease, disorder or clinically relevant abnormality that could have
             jeopardized the subject's appropriate participation in this study or obscure the
             effects of treatment

         20. Female subjects who were pregnant or nursing

         21. Two or more consecutive SMBG measures ≥ 250 mg dL-1 (13.9 mmol L-1) prior to
             randomization accompanied by clinical signs or symptoms of hyperglycemia prior to
             randomization, including weight loss, blurred vision, increased thirst increased
             urination, or fatigue