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.
Medication use in DM2
- Metformin is the preferred initial pharmacologic agent for the treatment of type 2 diabetes.
- Once initiated, metformin should be continued as long as it is tolerated and not contraindicated; other agents, including insulin, should be added to metformin.
- Early combination therapy can be considered in some patients at treatment initiation to extend the time to treatment failure.
- The early introduction of insulin should be considered if there is evidence of ongoing:
- Catabolism (weight loss)
- Symptoms of hyperglycemia
- A1c levels >10%
- Blood glucose ≥300 mg/dL
- A patient-centered approach should be used to guide the choice of pharmacologic agents. Considerations include cardiovascular comorbidities, hypoglycemia risk, impact on weight, cost, risk for side effects, and patient preferences
- Among patients with type 2 diabetes who have established:
- ASCVD: Atherosclerotic cardiovascular disease or indicators of high risk
- CKD: Kidney disease
- HF: Heart failure
- A sodium–glucose cotransporter 2 inhibitor (SGLT2i) or glucagon-like peptide 1 receptor agonist (GLP1a) with demonstrated cardiovascular disease benefit is recommended as part of the glucose-lowering regimen independent of A1c and in consideration of patient-specific factors.
- In patients with type 2 diabetes who need greater glucose lowering than can be obtained with oral agents, glucagon-like peptide 1 receptor (GLP1a) agonists are preferred to insulin when possible.
- Intensification of treatment for patients with type 2 diabetes not meeting treatment goals should not be delayed.
- The medication regimen and medication-taking behavior should be reevaluated at regular intervals (every 3–6 months) and adjusted as needed to incorporate specific factors that impact choice of treatment.