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Am Fam Physician. 2020;101(5):309-310

Clinical Question

Is linagliptin (Tradjenta) noninferior to glimepiride (Amaryl) in adults with poorly controlled type 2 diabetes mellitus?

Bottom Line

This study found that linagliptin is noninferior to glimepiride for reducing the risk of cardiovascular death, myocardial infarction, and stroke in adults with type 2 diabetes at an increased risk of cardiovascular disease. Although hypoglycemic events occurred significantly more often in patients treated with glimepiride, study-targeted levels of A1C (mean 7.2%) were consistent with levels previously shown to unnecessarily increase the risk of severe hypoglycemia and premature mortality. The Good Rx price (; accessed September 19, 2019) for a one-month supply of linagliptin is $378 vs. $3 for glimepiride. (Level of Evidence = 1b)


Clinicians have many options for second-line treatment to metformin monotherapy in adults with poorly controlled type 2 diabetes. The investigators identified adults with type 2 diabetes, an A1C of 6.5% to 8.5%, and high cardiovascular risk (e.g., established cardiovascular disease, multiple risk factors including hypertension, smoking, hyperlipidemia, age greater than 69 years, evidence of microvascular complications). Eligible patients randomly received (concealed allocation assignment) linagliptin (5 mg per day) or glimepiride (1 to 4 mg per day, titrated to achieve a target A1C of less than 7.5%). Additional medications were added as needed for persistent hyperglycemia. Individuals masked to treatment group assignment assessed all outcomes. Complete follow-up occurred for 96% of participants for a mean of 6.3 years.

Using intention-to-treat analysis, no significant difference occurred between the groups treated with linagliptin vs. glimepiride in the primary end point of cardiovascular death, myocardial infarction, or stroke (11.8% vs. 12.0%, respectively). There was also no significant difference between the two groups in all-cause mortality or study drop-out rates due to adverse events. Weight gain was significantly higher in the glimepiride group (3.4 lb [1.54 kg]). Rates of hypoglycemia, including severe events, were also increased in the glimepiride group (number needed to harm = 3 to 4 for at least one episode).

Study design: Randomized controlled trial (double-blinded)

Funding source: Industry

Allocation: Concealed

Setting: Outpatient (primary care)

Reference: Rosenstock J, Kahn SE, Johansen OE, et al.; CAROLINA Investigators. Effect of linagliptin vs glimepiride on major adverse cardiovascular outcomes in patients with type 2 diabetes: the CAROLINA randomized clinical trial. JAMA. 2019;322(12):1155–1166.

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