Assessing the Effect of Met DR on Plasma Glucose and PK in Subjects With T2DM

Inclusion criteria

• 18 to 70 (inclusive) years old at Visit 1 (Screening)
• Was diagnosed with type 2 diabetes mellitus with

• HbA1c between 6.0 to 9.5% (inclusive) for subjects managing their diabetes with:

i. Diet and exercise alone, or ii. A stable regimen (minimum of 2 months at Visit 1) of metformin alone, or iii. A stable regimen (minimum of 2 months at Visit 1) of DPP-4 inhibitor alone OR

• HbA1c between 6.0 to 8.5% (inclusive) for subjects managing their diabetes with a stable (minimum of 2 months at Visit 1) combination regimen of metformin and DPP-4 inhibitors
• Had normal renal function with an estimated glomerular filtration rate (eGFR) ≥90 mL/min/1.73 m^2 based on the Modification of Diet in Renal Disease (MDRD) equation
• Body mass index (BMI) of 25.0 to 40.0 kg/m^2 (inclusive) at Screening
• Male, or if female and met all of the following criteria:

• Not breastfeeding
• Negative pregnancy test result (human chorionic gonadotropin, beta subunit) at Visit 1 (Screening) (not applicable to hysterectomized females)
• Surgically sterile, postmenopausal, or if of childbearing potential, practiced and was willing to continue to practice appropriate birth control during the entire duration of the study
• Had a physical examination with no clinically significant abnormalities as judged by the investigator
• Ability to understand and willingness to adhere to protocol requirements
• If on chronic thyroid pharmacologic therapy, the dose must have been stable for at least 3 months prior to Visit 1 (Screening), and must have thyroid-stimulating hormone (TSH) test result in normal range at Visit 1 (Screening)

Exclusion criteria

• Had a clinically significant medical condition that could potentially affect study participation and/or personal well-being, as judged by the investigator, including but not limited to the following conditions:

• Hepatic disease
• Renal disease
• Gastrointestinal disease
• Endocrine disorder except diabetes
• Cardiovascular disease
• Central nervous system diseases
• Psychiatric or neurological disorders
• Organ transplantation
• Chronic or acute infection
• Orthostatic hypotension, fainting spells or blackouts
• Allergy or hypersensitivity
• Had any chronic disease requiring medication that was adjusted in the past 90 days (subjects could take acute intermittent over-the-counter medications such as Tylenol, if needed)
• Had any drug treatment that affects gastric pH (prescription or over-the-counter), including any antacids or medications such as Rolaids or Pepcid within 2 days of Visit 1 (Screening)
• Had major surgery of any kind within 6 months of Visit 1 (Screening)
• Had received a blood transfusion within 6 months of Visit 1 (Screening)
• Had a history of >5 kg weight change within 3 months of Visit 1 (Screening)
• Had clinical laboratory test (clinical chemistry, hematology, or urinalysis) abnormalities other than those expected in subjects with type 2 diabetes and judged by the investigator to be clinically significant at Visit 1 (Screening)
• Had a physical, psychological, or historical finding that, in the investigator's opinion, would make the subject unsuitable for the study
• Abused drugs or alcohol or had a history of abuse that in the investigator's opinion would cause the individual to be noncompliant with study procedures
• Had donated blood within 3 months of the date of the first dose of randomized study medication, or was planning to donate blood during the study
• Used insulin within 3 months of Visit 1 (Screening)
• Had received GLP-1 receptor agonists and/or thiazolidinedione treatment within 6 months of Visit 1 (Screening)
• Had known intolerance to metformin
• Had received any investigational drug within 2 months (or five half-lives of the investigational drug, whichever was greater) of Visit 1 (Screening)
• Had known allergies or hypersensitivity to any component of study treatment
• Was employed by Elcelyx Therapeutics, Inc. (that is an employee, temporary contract worker, or designee of the company)
• Smoked more than 10 cigarettes per day, 3 cigars per day, 3 pipes per day, used more than 1 can of smokeless tobacco per week, or used a combination of tobacco products that approximate nicotine doses equivalent to 10 cigarettes per day