Liraglutide found superior to sitagliptin for reduction of HbA1c in type 2 diabetics

Liraglutide offered superior glycemic control to sitagliptin in patients with type 2 diabetes who had inadequate glycemic control on metformin, according to a recent report in The Lancet.

A 26-week, randomized, parallel-group, open-label trial enrolled patients aged 18 to 80 years with type 2 diabetes mellitus who had inadequate glycemic control (glycosylated hemoglobin [HbA_1c] 7.5% to 10.0%) on metformin (>1,500 mg daily for >3 months). Treatment with subcutaneous liraglutide administered once daily at either 1.2 mg (n=225) or 1.8 mg (n=221) per dose lowered HbA_1c to a greater extent than 100 mg of oral sitagliptin administered once daily (n=219) [–0.60% (95% CI, –0.77 to –0.43; P.0001) for 1.8 mg and –0.34% (95% CI, –0.51 to –0.16; P.0001) for 1.2-mg liraglutide dose compared to sitagliptin]. Consequently, a greater proportion of patients receiving liraglutide achieved the HbA_1c goal of
Liraglutide, a glucagon-like peptide-1 (GLP-1) analog, supplies biologic activity similar to native GLP-1, and sitagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, prevents the enzymatic inactivation of GLP-1 and glucose-dependent insulinotropic polypeptide (GIP). GLP-1 and GIP, which are rapidly released after meals, increase glucose-dependent insulin secretion. Furthermore, GLP-1, also suppresses glucagon secretion, delays gastric emptying, and decreases appetite. Currently two GLP-1 analogs, liraglutide and exenatide, and two DPP-4 inhibitors, sitagliptin and saxagliptin, are approved for marketing by FDA.

The researchers note in their paper, “In accordance with the consensus algorithm for the treatment of type 2 diabetes mellitus by the American Diabetes Association and the European Association for the Study of Diabetes, our results support the use of liraglutide to achieve glycemic goals in patients with inadequate control on metformin.”

The current “consensus algorithm” or guidelines published in 2009 by the major American and European diabetes medical organizations recommend that selection of drug therapy for treatment of type 2 diabetes be based on a drug’s ability to reduce hyperglycemia (in particular, HbA_1c). Guidelines recommend that patients inadequately treated with metformin monotherapy (and lifestyle modification) should be initiated on either sulfonylureas or insulin. Pioglitazone and the GLP-1 analogs may also be selected and are listed as tier 2 drugs. However, DPP-4 inhibitors (as well as other common antidiabetic agents) get only cursory mention due to the consensus panel’s assessment that there is limited data supporting their efficacy.

In addition to its superiority on glucose lowering, this new trial suggests that liraglutide significantly reduces body weight to a greater extent than sitagliptin [–2.42 kg (95% CI, –3.14 to –1.70) for 1.8-mg liraglutide versus sitagliptin, and –1.90 kg (95% CI, –2.61 to –1.18) for 1.2- mg liraglutide versus sitagliptin]. Minor hypoglycemia was recorded in about 5% of patients in each treatment group.

The complete findings of this randomized controlled trial were published in the April 24, 2010, edition of The Lancet along with a detailed on-line appendix.

SOURCES
Pratley RE, Nauck M, Bailey T, et al; for the 1860-LIRA-DPP-4 Study Group. Liraglutide versus sitagliptin for patients with type 2 diabetes who did not have adequate glycaemic control with metformin: a 26-week, randomised, parallel-group, open-label trial. Lancet. 2010;375:1447–1456.

Nathan DM, Buse JB, Davidson MB, et al; American Diabetes Association; European Association for Study of Diabetes. Medical management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy: a consensus statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care. 2009;32:193–203.