MKSAP quiz: Initiating medication therapy

This month's quiz asks readers to evaluate a 54-year-old man who was diagnosed with type 2 diabetes mellitus 3 months ago and opted for lifestyle modifications initially. His repeat hemoglobin A1c level is 7.9%, and he would like it to be less than 7%.


A 54-year-old man is evaluated at a follow-up visit after being diagnosed with type 2 diabetes mellitus 3 months ago. His initial hemoglobin A1c level was 8.5%. He opted for lifestyle modifications initially, and he has lost 4.5 kg (10 lb) after making changes to his diet and increasing his activity level. His average blood glucose level currently is 180 mg/dL (10 mmol/L). Medical history is otherwise unremarkable.

On physical examination, blood pressure is 130/74 mm Hg and pulse is 70/min. BMI is 27. The examination is otherwise unremarkable.

His repeat hemoglobin A1c level today is 7.9%, but he would like it to be less than 7%. Results of other laboratory studies are within normal ranges.

Which of the following is the most appropriate management?

A. Continue current management
B. Initiate empagliflozin
C. Initiate liraglutide
D. Initiate metformin

Reveal the Answer

MKSAP Answer and Critique

The correct answer is D. Initiate metformin. This item is available to MKSAP 18 subscribers as item 3 of extension set 4 in the Endocrinology and Metabolism section. More information about MKSAP 18 is available online.

The most appropriate management is to initiate metformin. The American Diabetes Association (ADA) recommends a hemoglobin A1c goal of less than 6.5% to 7% in patients with diabetes mellitus who are early in the disease course and with few comorbidities. The American College of Physicians (ACP) recommends a hemoglobin A1c level between 7% and 8% in most patients with type 2 diabetes. More stringent targets may be appropriate for patients who have a long life expectancy (>15 years) and are interested in more intensive glycemic control with pharmacologic therapy despite the risk for harms, including but not limited to hypoglycemia, patient burden, and drug costs. This patient is early in the disease course and without comorbidities, and he desires tighter glycemic control than 3 months of lifestyle modifications alone has achieved. Pharmacologic therapy should now be added to his lifestyle modifications. The ADA and ACP recommend metformin as first-line therapy for all patients with type 2 diabetes without contraindications. This recommendation is based upon data from multiple studies demonstrating the effectiveness and safety of metformin. In addition, metformin is inexpensive.

The patient has had a reduction in his weight and hemoglobin A1c level with lifestyle modifications alone over a 3-month period. Despite this, his hemoglobin A1c level remains above the goal of less than 7%. Therefore, continuing his current management protocol would not be appropriate. Achieving glucose goals early in the disease course can reduce the risk for development of microvascular and possibly macrovascular complications. The addition of pharmacologic therapy at this time is necessary for him to reach his glycemic target.

The ADA and ACP consider empagliflozin and liraglutide second-line therapies after metformin. Among patients with type 2 diabetes who have established atherosclerotic cardiovascular disease or indicators of high risk, established kidney disease, or heart failure, a sodium–glucose cotransporter 2 inhibitor or glucagon-like peptide 1 receptor agonist with demonstrated cardiovascular disease benefit (such as empagliflozin or liraglutide) is recommended as part of the glucose-lowering regimen independent of hemoglobin A1C level and in consideration of patient-specific factors. This patient does not have an indication for these drugs at this time.

If the patient's hemoglobin A1c levels do not meet the target after 3 months of lifestyle modifications and metformin, dual therapy with metformin and other oral agents should be considered.

Key Point

  • Metformin is first-line therapy for all patients with type 2 diabetes without contraindications.