The ADA guidelines still recommend Metformin as the first drug for patients with diabetes type 2 (DM2). The advantages of Metformin are its efficacy in lowering A1c, being inexpensive, improving insulin resistance, potential weight loss, not causing hypoglycemia, and having the most extended clinical safety data – since its approval in 1957 in France and 1995 in the U.S.
If the patient has established or risk factors for cardiovascular disease, then a GLP1 agonist with proven CVD benefits is the recommended second-line medication. Examples are Ozempic, Victoza, and Trulicity. However, if a person with DM2 has heart failure or chronic kidney disease ― defined by LVEF <45%, eGFR 30-60, or urinary albuminuria >300 ― an SGLT2 inhibitor should be used. Such medications are Invokana, Jardiance, and Farxiga.
The ADA recommends the following drugs as the third line option: GLP1 agonist if already on Metformin + SGLT2 inhibitor and SGLT2 inhibitor if the patient is taking Metformin + GLP1 agonist. Any of the following agents could be fourth line therapies; sulfonylurea, basal insulin, DDP4 inhibitor, or TZD if heart failure is absent.
The above drug algorithmic guidance is general. The ultimate clinical decision is based on medication tolerability, cost, clinical setting, glucose control, comorbidities, and patient’s preference.
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