An Efficacy Study of Canagliflozin or Sitagliptin to Determine Glucose Variability in Mexican Participants With Type 2 Diabetes Mellitus Inadequately Controlled on Metformin

• Canagliflozin 300 mg (Drug), also known as JNJ-28431754: Participants will receive canagliflozin 300 mg oral tablet once-daily for 28 days.
• Sitagliptin 100 mg (Drug): Participants will receive sitagliptin 100 mg oral tablet once-daily for 28 days.
• Metformin (Drug): Participants will receive metformin at a stable dose of >= 1500 mg/day throughout the study including the washout period between each intervention.

Primary outcomes

• Change From Baseline in Glycemic Coefficient of Variation (CV) in Treatment Period 1 [Baseline up to End of Treatment Period 1 (Days 22 to 27)]: Continuous blood glucose monitoring was done in participants using continuous glucose monitoring (CGM) determined over a 6-day period (in order to obtain a continuous 72-hour reading) at baseline and after each active treatment. Glucose coefficient of variation (CV) was calculated based on CGM data dividing the standard deviation of blood glucose values by the mean of the corresponding glucose readings. The participants were analyzed according to treatment received in treatment period 2 as per the sequence reported in this outcome measure.
• Change From Baseline in Glycemic Coefficient of Variation (CV) in Treatment Period 2 [Baseline up to End of Treatment Period 2 (Days 66 to 71)]: Continuous blood glucose monitoring was done in participants using CGM determined over a 6-day period (in order to obtain a continuous 72-hour reading) at baseline and after each active treatment. Glucose coefficient of variation was calculated based on CGM data dividing the standard deviation of blood glucose values by the mean of the corresponding glucose readings. The participants were analyzed according to treatment received in treatment period 2 as per the sequence reported in this outcome measure.

Secondary outcomes

• Change From Baseline in Glycemic Standard Deviation (SD) for 24-hour Glucose Profile [Baseline up to End of Treatment Period 1 (Days 22 to 27) and End of Treatment Period 2 (Days 66 to 71)]: Glycemic standard deviation for 24-hour glucose profile (glycemic variability), as measured by CGM was determined over a 6-day period (in order to obtain a continuous 72-hour reading) at baseline and at the end of each active treatment. The participants who received the study drug in the treatment period 1 and 2 as per the sequence were reported in this outcome measure.
• Change From Baseline in Mean 24-hour Glucose Profile [Baseline up to End of Treatment Period 1 (Days 22 to 27) and End of Treatment Period 2 (Days 66 to 71)]: Mean 24-hour glucose profiles as measured by CGM was determined over a 6-day period (in order to obtain a continuous 72-hour reading) at baseline and at the end of each active treatment. The participants were analyzed according to treatment received in treatment period 1 and treatment period 2 as per the sequence reported in this outcome measure.
• Change From Baseline in Fasting Plasma Glucose Levels [Baseline up to End of Treatment Period 1 (Days 22 to 27) and End of Treatment Period 2 (Days 66 to 71)]: Fasting plasma glucose levels were determined over a 6-day period (in order to obtain a continuous 72-hour reading) at baseline and at the end of each active treatment. The participants were analyzed according to treatment received in treatment period 1 and treatment period 2 as per the sequence reported in this outcome measure.
• Change From Baseline in 2-hour Post-prandial Glucose (PPG) Levels [Baseline up to End of Treatment Period 1 (Days 22 to 27) and End of Treatment Period 2 (Days 66 to 71)]: 2-hour post-prandial glucose levels were determined over a 6-day period (in order to obtain a continuous 72-hour reading) at baseline and at the end of each active treatment. The participants were analyzed according to treatment received in treatment period 1 and treatment period 2 as per the sequence reported in this outcome measure.
• Percent Change From Baseline in Time During 24 Hours With Glucose 70 to 139 mg/dL [Baseline up to End of Treatment Period 1 (Days 22 to 27) and End of Treatment Period 2 (Days 66 to 71)]: Percent change from baseline in time during 24 hours with glucose levels 70 to 139 mg/dL was determined over a 6-day period (in order to obtain a continuous 72-hour reading) at baseline and at the end of each active treatment. The participants were analyzed according to treatment received in treatment period 1 and treatment period 2 as per the sequence reported in this outcome measure.
• Percent Change From Baseline in Time During 24 Hours With Glucose Greater Than (>) 140 mg/dL [Baseline up to End of Treatment Period 1 (Days 22 to 27) and End of Treatment Period 2 (Days 66 to 71)]: Percent change from baseline in time during 24 hours within the glucose levels >140 mg/dL was determined over a 6-day period (in order to obtain a continuous 72-hour reading) at baseline and at the end of each active treatment. The participants were analyzed according to treatment received in treatment period 1 and treatment period 2 as per the sequence reported in this outcome measure.
• Percent Change From Baseline in Time During 24 Hours With Glucose Level > 180 mg/dL [Baseline up to End of Treatment Period 1 (Days 22 to 27) and End of Treatment Period 2 (Days 66 to 71)]: Percent change from baseline in time during 24 hours within the glucose levels >180 mg/dL was determined over a 6-day period (in order to obtain a continuous 72-hour reading) at baseline and at the end of each active treatment. The participants were analyzed according to treatment received in treatment period 1 as per the sequence reported in this outcome measure.
• Percent Change From Baseline in Time During 24 Hours With Glucose Level Less Than (<) 70 mg/dL [Baseline up to End of Treatment Period 1 (Days 22 to 27) and End of Treatment Period 2 (Days 66 to 71)]: Percent change from baseline in time during 24 hours within the glucose levels < 70 mg/dL was determined over a 6-day period (in order to obtain a continuous 72-hour reading) at baseline and at the end of each active treatment. The participants were analyzed according to treatment received in treatment period 1 and treatment period 2 as per the sequence reported in this outcome measure.
• Change From Baseline in Time Spent With Glucose Level 70 to 139 mg/dL [Baseline up to End of Treatment Period 1 (Days 22 to 27) and End of Treatment Period 2 (Days 66 to 71)]: Time spent with the glucose level 70 to 139 mg/dL was determined over a 6-day period (in order to obtain a continuous 72-hour reading) at baseline and at the end of each active treatment. The participants were analyzed according to treatment received in treatment period 1 and treatment period 2 as per the sequence reported in this outcome measure.
• Change From Baseline in Time Spent With Glucose Level > 140 mg/dL [Baseline up to End of Treatment Period 1 (Days 22 to 27) and End of Treatment Period 2 (Days 66 to 71)]: Time spent with the glucose level > 140 mg/dL was determined over a 6-day period (in order to obtain a continuous 72-hour reading) at baseline and at the end of each active treatment. The participants were analyzed according to treatment received in treatment period 1 and treatment period 2 as per the sequence reported in this outcome measure.
• Change From Baseline in Time Spent With Glucose Level > 180 mg/dL [Baseline up to End of Treatment Period 1 (Days 22 to 27) and End of Treatment Period 2 (Days 66 to 71)]: Time spent with the glucose level > 180 mg/dL was determined over a 6-day period (in order to obtain a continuous 72-hour reading) at baseline and at the end of each active treatment. The participants were analyzed according to treatment received in treatment period 1 as per the sequence reported in this outcome measure.
• Change From Baseline in Time Spent With Glucose Level < 70 mg/dL [Baseline up to End of Treatment Period 1 (Days 22 to 27) and End of Treatment Period 2 (Days 66 to 71)]: Time spent with the glucose level < 70 mg/dL was determined over a 6-day period (in order to obtain a continuous 72-hour reading) at baseline and at the end of each active treatment. The participants were analyzed according to treatment received in treatment period 1 and treatment period 2 as per the sequence reported in this outcome measure.
• Change From Baseline in Percentage of 2 Consecutive Glucose Readings With < 70 mg/dL [Baseline up to End of Treatment Period 1 (Days 22 to 27) and End of Treatment Period 2 (Days 66 to 71)]: The percentage of 2 consecutive glucose readings with < 70 mg/dL were reported. The participants were analyzed according to treatment received in treatment period 1 and treatment period 2 as per the sequence reported in this outcome measure.

Sex: All, ages: 19 Years to 54 Years

Inclusion Criteria:

* Type 2 diabetes mellitus
* Inadequate glucose control while using metformin monotherapy (MET) for at least 8 weeks at stable daily doses of at least 1500 milligram (mg) before screening visit (Visit 1)

  a. Hemoglobin A1c (HbA1c) equal to (=) 7.5 percent (%) to 10.5% at Visit 1
* Adequate qualifying continuous glucose monitoring (CGM) reading during the pre-randomization (selection) phase
* Estimated glomerular filtration rate (eGFR) of at least 60 milliliter/minute (mL/min)/1.73 meter square (m\^2) at Visit 1
* Body mass index of 22 through 45 kilogram per meter square (kg/m\^2) at Visit 1

Exclusion Criteria:

* History of any of the following (at Visit 1):

  1. Diabetic ketoacidosis (DKA)
  2. Type 1 diabetes mellitus (T1DM)
  3. Pancreatic (for example, Beta-islet cell) transplantation
  4. Diabetes secondary to pancreatitis or pancreatectomy
  5. Personal history of, or ongoing, pancreatitis
  6. One or more episodes of severe hypoglycemia (requiring assistance from others), as documented in the history obtained at Visit 1
  7. Hereditary glucose-galactose malabsorption or primary renal glucosuria
* Repeated fasting plasma glucose (FPG) or fasting self-monitored blood glucose (SMBG) greater than (>) 270 milligram per deciliter (mg/dL) during the pre-treatment phase
* Treatment with any other oral or parenteral antidiabetic medications different from metformin monotherapy, including but not limited to Dipeptidyl peptidase-4 (DPP-4) inhibitors, Sulphonylureas, thiazolidinediones, insulins and Glucagon-like peptide-1 receptor agonist (GLP-1RAs); Sodium-glucose co-transporter 2 (SGLT-2) inhibitors and investigational agents
* Received an investigational drug or vaccine or used an invasive investigational medical device within 30 days before the planned first dose of study drug
* Current use of "natural medicines" or natural medicinal products for diabetes (for example, cactus-derived nutrients, celery)

Participant flow

Outcome results

• Change From Baseline in Glycemic Coefficient of Variation (CV) in Treatment Period 1 (Primary), Mean, Percentage of CV: Treatment Sequence AB -0.69 +/- 5.17; Treatment Sequence BA 0.24 +/- 10.23
• Change From Baseline in Glycemic Coefficient of Variation (CV) in Treatment Period 2 (Primary), Mean, Percentage of CV: Treatment Sequence AB -1.26 +/- 7.41; Treatment Sequence BA 0.77 +/- 6.16
• Change From Baseline in Glycemic Standard Deviation (SD) for 24-hour Glucose Profile (Secondary), Mean, mg/dL: Treatment Sequence AB -7.64 +/- 6.56; Treatment Sequence BA -8.40 +/- 11.07
• Change From Baseline in Mean 24-hour Glucose Profile (Secondary), Mean, mg/dL: Treatment Sequence AB -34.81 +/- 34.87; Treatment Sequence BA -39.56 +/- 39.79
• Change From Baseline in Fasting Plasma Glucose Levels (Secondary), Mean, mg/dL: Treatment Sequence AB -32.04 +/- 33.95; Treatment Sequence BA -34.48 +/- 32.94
• Change From Baseline in 2-hour Post-prandial Glucose (PPG) Levels (Secondary), Mean, mg/dL: Treatment Sequence AB -47.03 +/- 45.85; Treatment Sequence BA -43.36 +/- 48.00
• Percent Change From Baseline in Time During 24 Hours With Glucose 70 to 139 mg/dL (Secondary), Mean, Percent Change: Treatment Sequence AB 0.157 +/- 0.134; Treatment Sequence BA 0.191 +/- 0.224
• Percent Change From Baseline in Time During 24 Hours With Glucose Greater Than (>) 140 mg/dL (Secondary), Mean, Percent Change: Treatment Sequence AB -0.161 +/- 0.145; Treatment Sequence BA -0.216 +/- 0.257
• Percent Change From Baseline in Time During 24 Hours With Glucose Level > 180 mg/dL (Secondary), Mean, Percent Change: Treatment Sequence AB -0.235 +/- 0.204; Treatment Sequence BA -0.212 +/- 0.286
• Percent Change From Baseline in Time During 24 Hours With Glucose Level Less Than (<) 70 mg/dL (Secondary), Mean, Percent Change: Treatment Sequence AB NA +/- NA; Treatment Sequence BA NA +/- NA
• Change From Baseline in Time Spent With Glucose Level 70 to 139 mg/dL (Secondary), Mean, Minutes: Treatment Sequence AB 226.64 +/- 193.01; Treatment Sequence BA 275.64 +/- 323.39
• Change From Baseline in Time Spent With Glucose Level > 140 mg/dL (Secondary), Mean, Minutes: Treatment Sequence AB -231.98 +/- 208.27; Treatment Sequence BA -310.41 +/- 370.20
• Change From Baseline in Time Spent With Glucose Level > 180 mg/dL (Secondary), Mean, Minutes: Treatment Sequence AB -338.36 +/- 293.40; Treatment Sequence BA -305.69 +/- 412.30
• Change From Baseline in Time Spent With Glucose Level < 70 mg/dL (Secondary), Mean, Minutes: Treatment Sequence AB NA +/- NA; Treatment Sequence BA NA +/- NA
• Change From Baseline in Percentage of 2 Consecutive Glucose Readings With < 70 mg/dL (Secondary), Mean, Percentage of readings: Treatment Sequence AB NA +/- NA; Treatment Sequence BA NA +/- NA

Adverse events

Time frame: Up to 96 Days

Other adverse events by term

Limitations and caveats: The main limitation of the study was the sample size limited to demonstrate any significant difference.

• Study Protocol (PDF, 2017-07-31)
• Statistical Analysis Plan (PDF, 2018-08-13)

• Janssen Research & Development, LLC Clinical Trial, Study director, Janssen Research & Development, LLC