Dual vs Triple Therapy for Metformin Treatment Intensification in Type 2 Diabetes

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Early triple combination therapy with metformin, dapagliflozin, and saxagliptin offers better improvements in glycemic control than a dual therapy strategy with metformin and sitagliptin in patients with uncontrolled type 2 diabetes.

Early triple combination therapy with metformin, dapagliflozin, and saxagliptin offers better improvements in glycemic control than a dual therapy strategy with metformin and sitagliptin in patients with uncontrolled type 2 diabetes, according to study results published in Diabetes, Obesity and Metabolism.

Researchers conducted this 52-week active-controlled parallel-group phase 3b trial to compare the safety and efficacy of an intensification strategy of early triple-combination therapy with sodium-glucose cotransporter 2 inhibitor dapagliflozin and dipeptidyl peptidase-4 inhibitor saxagliptin and a dual therapy strategy with dipeptidyl peptidase-4 inhibitor sitagliptin in patients with inadequately controlled type 2 diabetes receiving metformin monotherapy.

In total, 461 patients (average age, 55.9 ± 9.2) with glycated hemoglobin (HbA1c) levels between 8% and 10.5% were randomly assigned to receive metformin plus both dapagliflozin and saxagliptin (n = 232) or only sitagliptin (n = 229). The groups had similar patient demographics and characteristics at baseline.

Overall, mean HbA1c at baseline was 8.8%. Compared with patients in the sitagliptin group, patients in the dapagliflozin and saxagliptin group on average experienced a significantly greater reduction in HbA1c levels at both week 26 (-1.07% vs -1.41%, respectively; P =.0008) and week 52 (-0.81 vs -1.29, respectively).

The between-group difference in adjusted mean HbA1c change from baseline increased from -0.34 at week 26 to -0.48 at week 52. Compared with the sitagliptin group, more patients in the triple therapy group reduced their HbA1c level to <7% by week 26 (25.1% vs 37.3%, respectively; P =.0034) and week 52 (19.5% vs 33%, respectively).

With regard to safety, both groups demonstrated similar levels of tolerance; 17 patients in the sitagliptin group had treatment-related adverse events compared with 22 patients in the triple-therapy group.

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Study limitations included a lack of a single add-on of dapagliflozin for comparison with the effects of a dual add-on.

“[When metformin] monotherapy alone becomes inadequate to control HbA1c,” said the researchers, “a strategy of early intensification with triple therapy using a combination of [dapagliflozin] plus [saxagliptin] may result in better, more durable, and well-tolerated glycemic control.”

Some authors disclosed ties to the pharmaceutical industry. Please see original resource for full list of disclosures.

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Reference

Handelsman Y, Mathieu C, Del Prato S, et al. Sustained 52-week efficacy and safety of triple therapy with dapagliflozin plus saxagliptin versus dual therapy with sitagliptin added to metformin in patients with uncontrolled type 2 diabetes [published online November 30, 2018]. Diabetes Obes Metab. doi:10.1111/dom.13594