1. Fotagliptin, a novel dipeptidyl peptidase-4 inhibitor (DPP4-i), was found to be noninferior to alogliptin and significantly more effective than placebo in meeting hemoglobin A1c (HbA1c) targets and reducing fasting blood glucose (FBG) in treatment-naive uncontrolled type 2 diabetes mellitus (T2DM) patients.
2. Fotagliptin was also found to be safe and well tolerated. Its use also resulted in significantly improved beta-cell function and fasting c-peptide concentration.
Evidence Rating Level: 1 (Excellent)
T2DM is among the most burdensome of communicable diseases with a rising prevalence worldwide. DPP4-is exert glycemic control by inhibiting the rapid degradation of incretin hormones and glucagon secretion, but under most guidelines, they are currently recommended as a second-line pharmacotherapy for glycemic control. The current randomized, multicenter, double-blind, and placebo-controlled approach recruited treatment-naive patients with uncontrolled T2DM (defined as HbA1c of 7.5 to 10.5% and fasting blood glucose of ≤ 13.9 mmol/L) in order to assess the efficacy and safety profile of a novel highly selective 12 mg once daily DPP4-i, fotagliptin. After a 4-week exercise and diet run-in period, patients were randomized to receive either fotagliptin (n = 230), alogliptin (n = 113), or a placebo (n = 115) for 24 weeks double-blind, followed by another 28 weeks of open-label treatment. Eighty-five percent of patients remained in this trial to its 52-week completion. At 24 weeks, fotagliptin was noninferior to alogliptin (p = .854), and both resulted in significant reductions in HbA1c percentages compared to placebo (ps < .0001; decreases of 0.7%, 0.72%, and 0.26% for fotogliptin, alogliptin, and placebo, respectively). Over 20% of patients receiving fotagliptin reached a HbA1C of ≤ 6.5% (p = .0003), and 37% were found to have HbA1cs of ≤ 7.0% (p < .0001). There was also a significant reduction in FBG after 24 weeks for both fotagliptin and alogliptin participants (p < .05). However, weight did not differ significantly between the groups and less than 1kg of weight loss was found in any group over the course of the study. Beta-cell function from baseline to week 24 showed significant improvements in patients receiving DPP4-is, and fotagliptin was associated with significantly improved fasting c-peptide concentration. With respect to safety, two fotagliptin participants experienced mild hypoglycemia over the course of the study, but both fotagliptin and alogliptin were found to be well tolerated. No deaths were reported, and all adverse events occurred in 4% of participants or fewer (3.1% for fotagliptin group, 3.6% for alogliptin group and 6.2% for placebo group). No episodes of pancreatitis occurred during the study period, although minimal increases in amylase and lipase levels were noted in weeks 4 to 24 for the treatment groups. Future studies surrounding fotagliptin should be repeated for longer durations in order to assess for potential cardiovascular protection, as well as its efficacy when used in conjunction with first-line therapy, metformin.
Click to read the study in BMC Medicine
Image: PD
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