Beta Cell Function in Type 2 Diabetes: Differential Effects of SGLT2 Inhibitors and GLIP-Receptor Agonists

Prior treatment

• Current regular use of DDP-4 inhibitors, insulin or GLP-1 RA or SGLT2-inhibitors
• Treatment with another investigational drug or other intervention within 4 months, or plan to enroll in another interventional study during their participation in this study
• Planned major surgery
• Use of weight loss medication, weight loss surgery.
• Use of glucocorticoids for chronic illness within 8 weeks prior to screening or likely to begin glucocorticoids during study period

Other illness

• Known allergic reactions to either the study medication
• Recent (within 6 months): MI, Stroke, Cerebrovascular accident or unstable angina or revascularization procedures, grade 3 or 4 heart failure

Lab values

• Poor general health, low kidney function (eGFR \< 45), abnormal liver blood tests (AST and ALT \> 3 times the ULN, Bilirubin 2 x ULN), serious cardiovascular, liver or renal disease, known proliferative retinopathy, type 1 diabetes, pancreatitis or pancreas cancer, medullary thyroid cancer, MEN2 (or family history of MEN2), current low hematocrit (\< 35% for men and 33% for women, frailty, at risk for falls, current (past six months) alcohol or substance use disorder, history of a non-traumatic bone fracture, amputation, organ transplant, HIV or COVID, or if the patient cannot complete study activities.

Age

• Cancer - History of active or untreated malignancy or in remission from a clinically significant malignancy for \< 5 years; exception: basal cell carcinoma of the skin.

Other

• Currently pregnant, planned pregnancy in the next 7 months or nursing/lactating.
• Study doctor considers subject a poor study candidate

• Agrees to participate (signs and dates the informed consent) and agrees to all study procedures and conditions of the protocol.
• Black (self-identified) patients with relatively recent onset (\< 15 years) DM2
• aged \>= 24 years of age (adults \< age 24 years old need additional resources to consistently participate, and may have different metabolism)
• HbA1c between 6.9% and 10%, inclusive
• BMI \> 23 and \< 45 kg/m2, and stable body weight over 2 months
• In good general health, as evidenced by medical history and physical examination. And not having any of the specific items of the exclusion criteria.
• Currently taking no diabetes medication or on stable doses (2 months) of metformin or metformin plus sulfonylureas without additional diabetes medication(s).
• Ability to take and agree to taking oral medication and to self-inject
• For persons of reproductive potential: negative pregnancy test, use of effective contraception for at least 1 month prior to screening, and agreement to use such a method during study participation, and for an additional 4 weeks after completing the use of the study drug. They will be counseled that if they wish to become pregnant, they should follow the standard practice of optimizing their blood glucose in preparation for pregnancy. Use of these study drugs are not considered standard of care for diabetes during pregnancy. Effective contraception includes tubal ligation, hysterectomy, oral, implanted or injected contraceptives, mechanical (IUD) and barriers (diaphragm, condoms, spermicides) methods.
• Agreement to adhere to Lifestyle Considerations (see section 5.3) throughout the study, including following a diabetic diet and maintaining a physical activity program