TAK-648 Multiple-Rising Dose Study in Healthy Japanese Participants and Non-Japanese Participants With Type 2 Diabetes Mellitus

Inclusion Criteria: Part 1: 1. Is an adult male or female and has a historical diagnosis of type 2 diabetes mellitus (T2DM) disease. 2. Is aged 18 to 65 years, inclusive, at the time of informed consent and first study medication dose. 3. Weighs at least 55 kg and has a body mass index (BMI) ≥23.0 kg/m\^2 and ≤35.0 kg/m\^2 at Screening. 4. Has a systolic blood pressure \>90 and ≤150 mm Hg and a diastolic blood pressure of \>60 and ≤90 mm Hg at Screening and at Check-in (Day -2). If out of range, may be repeated once for eligibility determination within a maximum of5 minutes. 5. Has a calculated creatinine clearance \>60 mL/min at Screening and Check-in (Day -2). 6. Has been treated for inadequate glycemic control with a stable dose of metformin for the least 8 weeks prior to Screening. 7. Has a glycosylated hemoglobin (HbA1c) level between 6.5% and 10.0%, inclusive at Check-in (Day -2). 8. Has a fasting C-peptide concentration ≥0.8 ng/mL at Screening. 9. Has no medical history of type 1 diabetes mellitus (T1DM), hypoglycemia unawareness, diabetic ketoacidosis or hyperosmolar coma. Part 2: 1. Is a healthy adult male or female of Japanese descent (born to Japanese parents and grandparents) and have lived outside of Japan for less than 5 years, inclusive. 2. Is aged 20 to 55 years, inclusive, at the time of informed consent and first study medication dose. 3. Weighs at least 45 kg and has a BMI from 17.0 to 25.0 kg/m\^2, inclusive at Screening. 4. Has a systolic blood pressure \>90 and ≤150 mm Hg and a diastolic blood pressure of \>60 and ≤90 mm Hg at Screening and at Check-in (Day -2). If out of range, may be repeated once for eligibility determination within a maximum of 5 minutes. 5. Has a calculated creatinine clearance \>60 mL/min at Screening and Check-in (Day -2). Exclusion Criteria: Part 1: 1. Has Screening or Check-in (Day -2) laboratory values of serum creatinine ≥1.5 mg/dL for males or ≥1.4 mg/dL \[females\] or abnormal creatinine clearance. 2. Has a history of T1DM, hypoglycemia unawareness, diabetic ketoacidosis, or hyperosmolar coma. 3. Has a history of any clinically significant retinopathy, which is defined as more than moderate nonproliferative diabetic retinopathy or any stage of proliferative diabetic retinopathy or any history of laser-treated retinopathy. 4. Has received any antihyperglycemic medication with the exception of metformin within the previous 12 weeks of Check-in (Day -2) or the subject has changed the dose of metformin within the previous 8 weeks of Screening. 5. Is expecting to receive, receiving or has received systemic glucocorticoid therapy for a duration longer than 5 days within the previous 12 weeks of Check-in (Day -2). Parts 1 and 2: 1. Has received any investigational compound within 30 days prior to the first dose of study medication. 2. Has received TAK-648 in a previous clinical study or as a therapeutic agent. 3. Has any significant medical histories or currently uncontrolled clinical conditions, which may not be safe for participants to participate in the study, may impact the ability of the participant to participate in the study, or may potentially confound the study results. The concerned significant medical histories and uncontrolled clinical conditions include (may not be limited to) cardiovascular (such as ischemic heart disease, heart failure, cardiomyopathy, clinically significant arrhythmia, uncontrolled or unstable blood pressure), central nervous system, hepatic or hematopoietic disease(s), renal dysfunction, metabolic or endocrine dysfunction, pulmonary diseases including serious allergy and asthma hypoxemia, seizures, or allergic skin rash. 4. Has a history of significant GI disorders manifested with persistent, chronic or intermittent nausea, vomiting or diarrhea, or has a current or recent (within 6 months) GI disease that would influence the absorption of drugs (eg, a history or malabsorption, severe esophageal reflux, peptic ulcer disease or erosive esophagitis with frequent \[more than once per week\] occurrence of heartburn). 5. Has diagnosis of major depression, bipolar disorder or anxiety disorders, or has a risk of anxiety, depression, or insomnia according to the investigator's clinical judgment per HAM-D17 at Screening or has received any medication to treat any psychological disorders within 1 year. 6. Has a risk of suicide according to the investigator's clinical judgment per C-SSRS at Screening or has made a suicide attempt in the past 6 months prior to Screening. 7. Has a known hypersensitivity to any component of the formulation ofTAK-648, or to a PDE4 inhibitor (eg, roflumilast) or Listerine strips. 8. Has a positive urine drug result for drugs of abuse at Screening or Check-in (Day -2). 9. Has a history of drug abuse (defined as any illicit drug use) or a history of alcohol abuse within 1 year prior to the Screening visit or is unwilling to agree to abstain from alcohol and drugs throughout the study. 10. Has taken any excluded medication, supplements, or food products. 11. If female, is pregnant or lactating or intending to become pregnant before, during, or within 12 weeks after participating in this study; or intending to donate ova during such time period. 12. If male, intends to donate sperm during the course of this study or for 12 weeks thereafter. 13. Has a history of cancer, except basal cell carcinoma that has been in remission for at least 5 years prior to Day 1. 14. Has a positive test result for HBsAg, anti-HCV, at Screening or a known history of human immunodeficiency virus infection. 15. Has used nicotine-containing products (including but not limited to cigarettes, pipes, cigars, chewing tobacco, nicotine patch or nicotine gum) within 6 weeks prior to Check-in (Day -2). Cotinine test is positive at Screening or Check-in (Day -2). 16. Has poor peripheral venous access. 17. Has donated or lost 450 mL or more of his or her blood volume (including plasmapheresis), or had a transfusion of any blood product within 30 days prior to Day 1. 18. Has a Screening or Check-in (Day -2) abnormal (clinically significant) ECG, including but not limited to those with evidence of prolonged QT/QTc interval at Baseline (eg, QTc interval \>450 milliseconds) or those at risk for QT prolongation (eg with a family history of long QT syndrome). Entry of any subject with an abnormal (not clinically significant) ECG must be approved, and documented by signature by the principal investigator or medically qualified subinvestigator. 19. Has abnormal Screening or Check-in (Day -2) laboratory values that suggest a clinically significant underlying disease or participant with the following laboratory abnormalities: ALT and/or AST \>2.5×ULN.