MKSAP quiz: Second-line therapy

This month's quiz asks readers to evaluate a 56-year-old woman with type 2 diabetes who is unhappy with her recent HbA1c value and has been working toward weight reduction without success.


A 56-year-old woman presents to the office to discuss management of her type 2 diabetes mellitus. She is unhappy with her recent HbA1c value. She adheres to the maximum dose metformin monotherapy, which she has been taking for 1 year. Additionally, she has been working toward weight reduction without success; however, weight loss remains a top priority for this patient. Medical history is significant for hypertension, dyslipidemia, and recurrent vulvovaginal candidiasis. Family history includes type 2 diabetes in her mother and sister.

On physical examination, vital signs are normal. Central obesity is noted. The remainder of the examination, including retinal examination and diabetic foot examination, is normal.

Laboratory studies show HbA1c value of 7.6% (goal <7.0%) and glomerular filtration rate greater than 60 mL/min/1.73 m2.

According to the Agency for Healthcare Research and Quality, which of the following is the most appropriate add-on therapy to supplement metformin for this patient?

A. Basal insulin
B. Glucagon-like peptide-1 (GLP-1) receptor agonist
C. Sodium-glucose transporter-2 (SGLT2) inhibitor
D. Sulfonylurea
E. Thiazolidinedione


MKSAP Answer and Critique

The correct answer is B. Glucagon-like peptide-1 (GLP-1) receptor agonist. This item is available to MKSAP 17 Digital and Complete subscribers as item 2 in Endocrinology and Metabolism section of Update 2. More information about MKSAP 17 is available online.

A GLP-1 receptor agonist is the most appropriate add-on therapy to metformin for this patient. This class of drugs includes exenatide, liraglutide, lixisenatide, albiglutide, dulaglutide. The patient identifies glycemic control and weight loss as her goals of the visit. Diabetes medications associated with the maintenance or loss of weight are metformin, dipeptidyl peptidase-4 (DPP-4) inhibitors, GLP-1 receptor agonists, and sodium-glucose transporter-2 (SGLT2) inhibitors. Sulfonylureas, thiazolidinediones, and insulin are associated with weight gain and are therefore not optimal add-on agents for this specific patient based on her individualized goals of care. Drugs in each category are listed in Table 1 of the referenced article.

Based on a recently published comparative effectiveness review from the Agency for Healthcare Research and Quality, there is moderate to strong evidence that the combinations of metformin plus a GLP-1 receptor agonist and metformin plus an SGLT2 inhibitor (range in between-group differences of −1.8 to −3.6 kg [−3.9 to −7.9 lb]) were both favored over metformin monotherapy based on a weight loss outcome. Addition of one of these agents to metformin monotherapy may help to achieve this patient's goals of improvement in HbA1c and weight loss.

Of these two options that are associated with weight loss, GLP-1 receptor agonist therapy and SGLT2 inhibitor therapy, GLP-1 receptor agonist therapy is the best choice in this patient owing to her history of recurrent vulvovaginitis. SGLT2 inhibitor therapy is associated with an increased risk of genital mycotic infections. Thus, in this patient with recurrent vulvovaginal candidiasis, this class should be avoided.

Key Point

  • Evidence on comparative outcomes associated with different medication classes can be used to facilitate personalized treatment choices for patients with type 2 diabetes mellitus.