The 2020 clinical guideline from the American Diabetes Association (ADA) recommends early combination therapy for patients with type 2 diabetes who do not achieve glycemic control within 3 months and for those with co-existing chronic kidney disease (CKD) or cardiovascular disease (CVD).

The guideline update, performed by the ADA Professional Practice Committee based on a review of evidence published up to September 2019, was summarized by Kacie Doyle-Delgado, DNP, APRN, and colleagues from Mark’s Hospital and St. Mark’s Diabetes Center, Salt Lake City, Utah, in the Annals of Internal Medicine.

Metformin is still the preferred initial pharmacologic agent for most type 2 diabetes patients without stage 4 or 5 CKD, advanced heart failure, or a history of lactic acidosis. Second-line medication options include sodium-glucose cotransporter 2 (SGLT2) inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1 RAs), dipeptidyl peptidase-4 (DPP-4) inhibitors, thiazolidinedione, sulfonylureas, and basal insulin.

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Early combination therapy should be initiated for patients who do not achieve glycemic control within 3 months and/or for those with CKD or CVD, the authors wrote. GLP-1 RAs are preferred to starting insulin when possible. Early insulin therapy should be considered when signs and symptoms indicate excessive, uncontrolled hyperglycemia. Clinicians should individualize the choice of agent according to patient characteristics (eg, CKD, CVD, or a tendency for specific adverse effects), preferences, and drug-specific effects.

For patients with type 2 diabetes who have CKD, heart failure, or who are at high-risk for atherosclerotic CVD, clinicians should consider a SGLT2 inhibitor or GLP-1 RA with CVD benefits, according to the guideline. The recommendation was based on results from recent major trials of SGLT2 inhibitors (including, EMPA-REG OUTCOME, CANVAS, CREDENCE, and DECLARE-TIMI 58) and GLP-1 RAs (LEADER, SUSTAIN, PIONEER, EXSCEL) that examined cardiovascular and renal outcomes.

In their synopsis, the authors also discussed insulin therapy, including the proper uses of basal insulin, prandial insulin, concentrated insulins, inhaled insulin, and combination injectable therapy. The authors emphasized that insulin therapy should be discussed with patients as a way to improve therapy rather than portrayed as a personal failure.

Disclosure: Please see the original reference for a full list of authors’ disclosures.


Doyle-Delgado K, Chamberlain JJ, Shubrook JH, Skolnik N, Trujillo J. Pharmacologic approaches to glycemic treatment of type 2 diabetes: synopsis of the 2020 American Diabetes Association’s standards of medical care in diabetes clinical guideline. Published online September 1, 2020. Ann Intern Med. doi:10.7326/M20-2470